Semester 1 Flashcards
(198 cards)
1
Q
Are hormones found at high or low concentrations in the blood?
A
Low
2
Q
True or false:
Some hormones require days to exert their physiological effects
A
True
3
Q
What best describes a paracrine signal?
A
It acts on an adjacent cell
4
Q
True or false:
All endocrine organs are made up of a single cell type
A
FALSE
5
Q
What active hormones can be formed from the peptide hormone precursor POMC?
Depending on how you cleave POMC effects what products you get
A
ACTH - adrenocortiocotrophic hormone
CLIP - corticotropinlike intermediate lobe peptide
aMSH or bMSH - melanocyte stimulating hormone
B lipotropin
Y lipotropin
B endorphin
6
Q
What difference would you expect to see in the cellular morphology of endocrine cells that secrete a) peptide vs b) steroid hormones?
A
Peptide hormones - dark stained vesicles near cell surface awaiting sign for exocytosis
Large Golgi, ER and ribosomes (dark stained)
Steroid hormones - cells may contain lipid droplets that can be used for de novo generation of steroid hormones
7
Q
Which group of hormones is NOT stored prior to secretion?
A
Steroids
Lipophilic (steroid ring structure and fatty acid tail) can move straight through membrane without needing to be transported through it
8
Q
What hormone is subject to post translational modification?
TSH, testosterone or progesterone?
A
TSH as it is a peptide hormone
The other 2 are generated from cholesterol, steroid hormones. Don’t need to be translated!
9
Q
Which of the following hormones is secreted by the hypothalamus?
Oestrogen, prolactin, TRH or T3?
A
TRH - Because it is a releasing hormone! Causes pituitary to release something
Oestrogen produced in ovaries, prolactin in pituitary and T3 from thyroid
10
Q
Consider the negative feedback loop regulating cortisol secretion.
What would be the effect of removal of ACTH on the secretion of a) cortisol and b) CRH
A
decrease in cortisol and increase in CRH.
If we remove ACTH we won’t get any stimulation of adrenal cortex cells and they won’t produce any cortisol!
If there’s no cortisol, there’s no negative feedback system, nothing to tell hypothalamus not to release CRH, so CRH goes up!
11
Q
How would blockade of the pituitary portal circulation effect secretion of a) follicle stimulating hormone, b) prolactin and c) oxytocin?
A
A) FSH - levels will decrease as hypothalamus can’t communicate with anterior pituitary that produces FSH
B) prolactin - levels will decrease as it is also produced by anterior pituitary
C) oxytocin - will stay the same as it is produced from posterior pituitary which is stimulated by nerves! Doesn’t use portal circulation like anterior pituitary so isn’t affected!
12
Q
Why do hormones become so prominent during puberty?
A
Get a protein called KISS1 - turns on the signalling.
GRH is turned on, hypothalamus starts producing it. Goes to anterior pituitary, stimulates FSH production and LH.
13
Q
What are the events that occur in the target cell that cause the effects that we see as a result of the hormones testosterone and dihydrotestosterone?
A
They are steroid hormones
So inside the cell transcription will be turned on!
14
Q
What is the function of inter phase in the cell cycle?
A
It’s when the cell does the majority of its growing
15
Q
What is NOT part of inter phase?
A
Pro phase
(Cell cycle phases are Gap 1, Gap 2 and Mitotic M phase and G0)
16
Q
During the first mitotic phase of Meiosis, the 2 daughter cells produced have what?
A
Identical DNA
2n DNA = 46 chromosomes! (NOT chromatids, a chromatid is half a chromosome)
17
Q
What’s it called when you create diversity in homologous chromosome crossing over? (Recombination)!
A
Crossing over
18
Q
Where does Spermatogenesis occur?
A
Seminiferous tubules
19
Q
Where are the spermatogonia located within the seminiferous tubules?
A
Between the Sertoli cells and close to the basement membrane
20
Q
What process occurs as the spermatocytes move towards the lumen of the seminiferous tubules?
A
Differentiation - they become more specialised
21
Q
Oogenesis occurs in which structure?
A
Ovary - secondary oocyte will then move down the Fallopian tube
22
Q
What highlights the difference between spermatogenesis and oogenesis?
A
The location of where the processes occur
Whether we are born with the gametes
Movement of the stem cells within the sex organ
23
Q
What are the roles of calcium?
A
Structural in bone and teeth
Blood clotting
Muscle contraction
Exocytosis
Cell to cell adhesion
Intracellular signalling cascades - cofactors and secondary messengers
Oocyte fertilisation
24
Q
True or false:
Type 1 diabetes mellitus can be treated by dietary intervention
A
False
You treat it with insulin injection as it is an autoimmune disorder (get destruction of cells in islets of langerhaans so they can’t produce insulin)
25
True or false:
Blood glucose of 8mmol/L would inhibit insulin secretion
False
You would expect 8mmol/L of blood glucose after you’ve eaten a meal = insulin release to taken glucose from blood into cells so they can use it
26
True or false m:
Conversion of glucose to glycogen is an example a a catabolic reaction
False
That is an anabolic reaction!
A catabolic reaction is the breakdown of a large molecule
27
Why is it important to routinely measure urinary protein levels in patients with diabetes mellitus?
Gives us a good idea that the patient hasn’t been lying for the rest of month and so blood glucose stays controlled
Causes of protein in urine (proteinuria): poor kidney function
Prolonged elevation of glucose in blood - in tissues like liver, skeletal muscle and adipose tissue
Prolonged high glucose means it’s covalently linked to proteins (glycosylation) in the tissues - can prevent protein function. Especially in peripheral nerves and kidney, leads to protein in filtrate.
28
How might the anti inflammatory properties of these glucocorticoid hormones be used therapeutically while minimising possible metabolic side effects?
Glucocorticoids in blood - systemic side effects, want to minimise effects everywhere
The trick is to deliver a high concentration of the drug to where you want the action to happen and not in the bloodstream
The drug is a cortisol or a glucocorticoid analogue, therefore it does NOT participate in the negative feedback system = prolonged high concentration of glucocorticoid
29
ALWAYS SAY WHERE IT IS LOCATED, WHERE IT PHYSICALLY HAPPENS AND HOW ITS REGULATED BY HORMONES
Spermatogenesis is a process that produces …
During this the process, the stem cells that produce spermocytes called … undergo … to produce spermocytes
It is regulated by … which stimulates the production of … and …
It occurs in the … where the spermatogenic cells produce …
Spermocytes
Spermatogonium
Meiosis
GRH - gonatrophin releasing hormone
LH and FSH
Seminiferous tubules
Sperm
30
What is deposition?
Process by which osteoblasts incorporate calcium into hydroxyapatite in the construction of bone
31
What is resorption?
Process by which osteoclasts BREAK DOWN bone and release the minerals - resulting in a transfer of calcium from bone to blood
= dissolves hydroxyapatite
32
What is reabsorption?
Movement of constituents from the lumen of a tubule back into circulation
33
What is excretion?
Removal of constituents of fluid from body due to lack of ability to reabsorb them from kidney tubule
34
What is demineralisation?
Breakdown of calcium phosphate (hydroxyapatites) present on the surface of bone
35
What is the extracellular fluid ECF?
Body fluid that is NOT contained in cells
Found in blood, lymph, body cavities lined with serous (moisture exuding) membrane, muscular body tissues
36
What is a G protein coupled receptor?
7 transmembrane receptor protein located in the cell membrane that binds extracellular substances and transmits signals from these substances to an intracellular molecule called a G protein (guanine nucleotide binding protein)
37
Is vitamin D deficiency related to rickets?
YES
Bow legs form in children as you’ve got soft parts of bone and you’re pressing down with weight!
It’s about differentiation of those cells
Parathyroid hormone and vitamin D are important in the formation of osteoblasts = builds bone. Therefore vitamin D deficiency could lead to rickets
38
What is the shape of the structural unit of the liver? And what is this unit called?
What feature of these units makes them suited to their job?
Forms a hexagonal shape.
Called a lobule.
Very thin walled sections, only one or two layers of hepatocytes lining each sinusoid = increases the uptake of hepatocytes = large surface area = essential to screen all the blood coming in from GI tract
Also have large numbers of sinusoids = large surface area = happens quickly
39
What are the functions of the liver?
Red blood cell (erythrocytes) turnover
Digestion (primary function of liver is to produce bile)
Storage
Detoxification
Hormone production
Major site of production of new cholesterol
40
What does the liver store?
Glycogen
Fat
Steroid hormones (vitamins A, B12, D, E and K)
Minerals iron and copper
41
What hormone elicits the release of the secondary oocyte from the Graafian follicle?
LH luteinising hormone
A large build up of LH in the anterior pituitary it released when oestrogen levels reach high enough concentration
42
Pituitary gigantism if usually caused by an adenoma of the pituitary gland, what effect does the tumour have?
Increased growth hormone production and release
Growth hormone stimulates the differentiation of chrondrocytes and ossification of the cartilage at the epiphysis
43
Spermatogenesis occurs in the …
Seminiferous tubules
44
During the menstrual cycle which structure produces progesterone?
Corpus luteum
45
During pregnancy which structure produces progesterone?
Placenta
It also secretes human chorionic gonatropin (hCG), relaxin, corticotropin releasing hormone, human chorionic somatotomammotropin (hCS)
46
Which part of the spermatozoa provides ATP required for motility and metabolism?
Middle piece
This piece houses mitochondria which are responsible for generating ATP required for cellular metabolism and motility
47
Calcitriol production by C1 a hydroxylase in the kidney is stimulated by which hormone?
Parathyroid hormone (PTH)
PTH stimulates the production of calcitriol through an increase in c1 alpha hydroxylase expression levels
48
Secretion of … from the … regulates the release of follicle stimulating hormone (FSH) from gonadotroph cells of the …
GnRH
Hypothalamus
Anterior pituitary
49
WHAT OCCURS DURING PERIODS OF LOW EXTRACELLULAR CALCIUM CONCENTRATION:
1. Detection of low Ca2+ concentration by … on chief cells
2. Rapid release of … into the blood
3. Stimulation of bone resorption by the action of … and reabsorption of calcium from the …
4. Activation of … in the kidney, increasing … levels
5. Increases expression of calcium transporters in the … to increase absorption of calcium from the …
Calcium sensing receptors
Parathyroid hormone PTH
Osteoclasts
Kidney tubule
C1 a hydroxylase
Calcitriol
Gut epithelium
Diet
50
99% of calcium is stored in bone. What are the MAIN ways in which calcium regulation occurs in the body?
Absorption from GI tract, bone resorption and deposition, excretion and reabsorption from the kidney
51
What is true about steroid hormones?
They are synthesised from cholesterol
52
What hormone is NOT secreted into the primary capillary bed of the pituitary portal circulation?
Luteinising hormone LH
53
What hormone is NOT secreted from the human adrenal gland?
Progesterone
54
What is INCORRECT about Cushing’s syndrome?
Patients have hypoglycaemia
55
What kind of hormone is human growth hormone hGH?
Peptide - 191 amino acid peptide chain that is cleaved before it can be active at its receptor
56
What is the function of the hormone inhibin?
Inhibits follicle stimulating hormone FSH release
57
Ovulation occurs when oocyte is released from a ruptured … follicle
Mature of Graafian (point at which it bursts)
58
The corpus leuteum produces progesterone in NON pregnant females, what is the function of progesterone?
Stimulates growth of blood vessels that supply the endometrial lining
59
In a pregnant female which hormone prevents the degradation of the corpus leuteum into a corpus albicans?
Human chorionic gonadotropin hCG - released from placenta
60
What hormone is secreted periodically through the day?
Growth hormone releasing hormone GHRH
61
Which hormone stimulates the development and differentiation of spermatozoa and which cells is it released from?
Testosterone from Sertoli cells
And follicle stimulating hormone from gonadotroph cells
62
Human growth hormone has 2 distinct mechanisms of action. Which of these is NOT a direct action?
Differentiation of chondrocytes
Growth hormone released from pituitary goes to tissues and liver. It has effect on the liver that makes it produce insulin like growth factor 1.
63
Which hormone stimulates development of primary follicles?
Follicle stimulating hormone FSH
( LH is required for ovulation!)
64
What is required for the production of oestrogen by granulosa cells?
FSH and LH and the theca cells
65
A patient complains of aches and pains in his hands, headaches and swelling. The doctor orders a glucose tolerance test to be performed. Why?
What might explain these symptoms?
The doctor suspects that hGH is dysregulated. A glucose tolerance test will increase blood glucose concentrations which should reduce hGH and IGF1 levels
Increased hGH acts on the liver to produce IGF1. IGF1 then acts on bone to increase cell proliferation which causes swelling of joints and explains the pain in joints.
Increased hGH stimulates hGH receptors on cells in epiphyseal plate, stimulating cell proliferation. An increase in bone cell number at the end of bones can reduce space between bones = joint pain.
66
What might cause altered regulation of growth hormones?
Pituitary adenoma - an anterior pituitary tumour can increase the amount of hormones synthesised and released.
As somatotrop cells constitute a large percentage of the cells of anterior pituitary this is most likely to produce more hGH and as a result IGF1.
67
What is not an indirect action of hGH alone?
Bone growth
hGH can bind to receptors in epiphyseal plate of bones in young and growing animals = cell proliferation and maturation.
This can be influenced indirectly through IGF1.
68
What are the 2 distinct mechanisms of action for human growth hormone?
Direct - through action on growth hormone receptors
Indirect - through expression and release of IGF1 insulin like growth factor 1
69
What is the main function of the liver?
Filter the blood
70
What brings nutrient rich blood from GI tract to the liver?
Hepatic portal vein - but it has low levels of oxygen
71
Why is it important that the liver is positioned downstream of the GI tract?
The liver contains many metabolising enzymes which can modify ingested toxins so that they are rapidly excreted from the body
72
What happens to excess carbohydrates in the liver?
They are stored in the form of glycogen through a process called glycogenesis
If blood concentrations are in a normal range then the body stores glucose as glycogen
73
What is NOT synthesised by the liver?
Erthropoietin EPO - it is synthesised mainly by the kidneys
74
What is the role of the gall bladder?
Store + concentrate bile
it is a muscular sac which collects bile from the cystic duct between meals. It is where reabsorption of water and ions occurs, therefore concentrating bile.
Bile can be stored there for up to 12 hours
75
What is false about the gallbladder?
Contraction of the muscular gallbladder ejects bile through the common bile duct and into the stomach
76
What is false about bilirubin?
Bilirubin is derived from liver cholesterol molecules
77
Toxins and endogenous waste products are excreted in the liver through … of amino acids such as … to make the products more … and therefore easier to excrete in the urine and faeces
Conjugation
Glycine
Soluble
78
What is incorrect about bile salts?
Primary bile salts are mainly conjugated - generated from bile acids in hepatocytes. Primary bile acids are un conjugated and synthesised from cholesterol in hepatocytes. They are the most toxic.
Bile acids are conjugated (eg glycine) to generate bile salts.
Conjugation makes them more hydrophilic, allowing them to create a film around a globule of fat and cholesterol to increase solubility.
79
What is true regarding bile salts?
Bile salts increase the solubility of fat by creating lipid globules - formation of globules allows bile salts to surround the globule with their hydrophilic side facing outwards. This increases the surface area so that lipases from the pancreas can digest fats more rapidly.
95% bile salts are reabsorbed and recycled - they are recycled through absorption and carried in blood back to liver where they become secondary bile salts, often un conjugated
80
What must a hormone interact with to cause its effect?
Receptor
81
Many types of cells are responsive to the SAME hormone. What is the explanation for this?
Cells have receptors that respond to the same hormone but in a different way and may be expressed on the cell surface in different quantities
82
Where are the cells that are responsive to hormones located?
At locations in close proximity to where they are produced
All around the body
On specific cells that can react to the hormone specifically
At locations distant to where they are produced
83
What is NOT stored in the liver?
Insulin - it is synthesised on demand
84
What is the most common plasma protein (70% of all plasma protein) and is responsible for the colloid osmotic pressure of blood?
Albumin
85
What is true about Bilirubin?
It is an orange bile pigment that is one of the end products of haemoglobin breakdown in hepatocytes
It is conjugated by UDP- glucuronosyltransferases for excretion. It is excreted as stercobilin which gives faeces brown colour.
Mutation of these enzymes can lead to development of Gilbert’s Syndrome - a cause of pre hepatic jaundice
95% bilirubin is reabsorbed in the duodenum
It is metabolised in the small intestine by bacteria and 5% is eliminated in the faeces.
86
Secretin is released in response to what?
Acid in the duodenum, which allows it to stimulate bile secretion
Secretin stimulates the 2nd secretion which includes HCO3- carbonate ions that neutralise acid entering the duodenum from the stomach. This can double bile secretion for up to several hours post meal
Secretin only affects bile production by epithelial cells of ductules abs bile duct, it has NO effect on hepatocytes!
87
Cholecystokinin CCK is released into the …when fats enter the … stimulating contraction of the …
Blood
Duodenum
Gallbladder
CCK is the most effective stimulator of the rhythmic gallbladder contractions which cause emptying of bile in the gallbladder into the common bile duct
Relaxation of the sphincter of Oddi is required for effective emptying
88
Bile is secreted by hepatocytes directly into the…
Bile canaliculi
They are located between hepatocytes and allow bile to be secreted directly into them in a constant flow.
Bile then flows into ductules (part of portal triad) to the common hepatic duct - supplies the gallbladder.
Then flows into the common bile duct - supplying bile to the duodenum
89
Why do hepatocytes line the sinusoid directly with a single cell thick layer?
To enhance the movement of particles from the blood into bile
These cells contain enzymes which metabolise chemicals such as hormones and drugs to make them more hydrophilic to enable excretion
90
What is the cause of gallstones?
Excessive absorption of water FROM the bile
Cholesterol is almost completely insoluble so bile salts and lecithin increase solubility by forming micelles. When bile contracts in the gallbladder, all 3 are concentrated and therefore all stay in solution.
Solid accumulations of bile salts and cholesterol are formed when the balance of bile salt: cholesterol: lecithin changes.
Cholesterol in bile is partly proportional to intake in diet (liver synthesises it too from fat) so high prolonged cholesterol levels leads to high chance of gallstones
Additional causes may be inflammation of gallbladder mucosa = abnormal reabsorption of bile salts and water = precipitation of cholesterol and progressive build up in gallbladder = eventual generation of a gall stone.
91
Male reproductive system summary:
Testosterone decreases release of … and …
Inhibin decreases release of …
LH stimulates … secretion
Together with testosterone, … stimulates Spermatogenesis
Sertoli cells secrete … ABP
Leydig cells secrete …
GnRH and LH
FSH
Testosterone
FSH
Androgen binding protein
Testosterone
92
What does the hormone dihydro testosterone DHT stimulate?
(Male reproductive system)
Male pattern of development (before birth)
Enlargement of male sex organs and expression of male secondary sex characteristics (starting at puberty)
Anabolism (protein synthesis)
93
What could cause male infertility?
50% of infertility cases are due to abnormal male reproductive system
Spermatogenesis defect: decreases gonadotrophin secretion (e.g hyperprolactinaemia)
Testis malfunction: cryptorchidism - undescended testes
Genetic: eg. klinefelter’s syndrome, 47XXY karyotype
Physical damage: eg to blood testis barrier
94
The sinusoids of the liver are … capillaries.
Nutrient Rich … blood from … (GI tract)
Oxygenated blood from …
All drain into … then eventually into hepatic vein
… cells reside here (macrophages = immune function). Kupfer cells … old red blood cells generating … … and …. Iron is released for …
Very permeable
Deoxygenated
Hepatic portal vein
Hepatic artery
Common central vein
Kupfer
Phagocytose
Iron
Globin
Bilirubin
Erythrocyte precursor generation
95
The gallbladder structure:
Sodium and chloride ions will move … along with water and … will move in.
Means you will get a concentrated … solution in there.
Water passes all the way out of … so muscular sac doesn’t end up …
Out
Bicarbonate ions HCO3-
Alkaline
Basolateral surface
Swollen
96
How does the liver maintain plasma glucose?
How is glycogen stored?
Breakdown of glycogen to glucose by glycogenolysis
Glucogenic amino acids broken down to generate glucose via gluconeogenesis GNG
Release glucose directly into bloodstream
Under conditions oh high blood glucose (after a meal) glucose is converted to glycogen and triglycerides for storage
97
What is the role of the liver in synthesis, breakdown and storage?
Dietary fat processed to generate very low density lipoproteins VLDL, generated from triglycerides, apolipoproteins abs cholesterol
Cholesterol
Bile salts
Fatty acids are broken down to generate ATP
Hepatocytes store some triglycerides
98
What is bile?
A secretion of the liver consisting of water, bile salts, bile pigments, cholesterol , lecithin and several ions
Each day hepatocytes secrete 250-1000ml of bile
99
Conjugated bile benefit?
Eg. Glycocholic acid
Conjugated bile acid is more soluble so easily recycled back into body!
Makes it more soluble in water = helpful for transport
100
What can detoxification by the liver do?
Can chemically change or secrete thyroid hormones and steroid hormones such as oestrogens and aldosterone
They need to become LESS lipophilic and more hydrophilic. Conjugation process can make this happen
101
Bile secretion:
Secretin is released in response to … in the …
Cholecystokinin CCK is released in response to … in the …
Acid
Duodenum
Fat
Duodenum
102
How does the liver act as a gland?
Synthesises angiotensinogen
Synthesises abs releases thrombopoietin TPO (platelets)
Synthesises and activates vitamin D
103
What are the 4 causes of gallstones?
Too much absorption of water from bile
Too much absorption of bile acids from bile
Too much cholesterol in bile
Inflammation of epithelium
104
What is jaundice?
Yellowish colouration of the sclera of the eye, skin and mucous membranes caused by accumulation of bilirubin (breakdown product of erythrocytes)
Light stools and dark urine accompany other symptoms
105
What are the main functions of the liver and gallbladder?
Liver metabolises carbohydrates, lipids and proteins
It synthesises bile used in the digestion and absorption of dietary fats and cholesterol in the small intestine
It maintains blood glucose levels
It produces blood proteins
It stores certain vitamins and minerals until needed by the body
The gallbladder stores and concentrates bile
106
Bile is produced by … and secreted into the …
Secretin is released in response to … in the duodenum. It stimulates bile secretion by … and can double bile production for up to … hours after a meal.
Bile drains into the … to be stored in the … where it is concentrated.
Cholecystokinin is released in response to … in the duodenum.
Emptying starts by … … of the gallbladder wall stimulates most strongly by … but also by … and … nerve stimulation.
Effective emptying requires simultaneous … of the Sphincter of Oddi.
Hepatocytes
Bile canilliculi
Acid
Bile ductules
Several
Hepatic duct
Gallbladder
Fat
Rhythmic contractions
Cholecystokinin
Vagal, Enertic
Relaxation
107
What are the functions of the Sertoli cells?
What is their endocrine function?
Joined by tight junctions (that hold cells together) forming blood testis barrier
Nourishes Spermatocytes, spermatids and sperm
Phagocytose excess spermatid cytoplasm as they develop
Produce fluid for sperm transport
Endocrine: secrete the hormone inhibin
Regulate the effects of testosterone and FSH (anterior pituitary regulates cells and controls production of inhibin)
108
What are the physiological effects of testosterone?
Stimulates descent of testes before birth
Part of negative feedback loop to control sperm production
Controls secondary male characteristics: beard growth, voice deepening
Anabolism - driving protein synthesis = more muscle mass = males generally heavier than females
At puberty there is a massive increase in concentration of testosterone, induces secondary sex characteristics
109
What is testosterone?
It is an androgen: binds to androgen receptor
Synthesised from cholesterol (acts via a nuclear hormone receptor)
Secreted by the Leydig cells of the testes
In prostate, the enzyme 5a reductase converts testosterone to dihydro testosterone (important in secondary sex characteristics)
110
What does the spermatozoa contain?
23 chromosomes
Acrosome contains enzymes for degradation, helps it penetrate the secondary oocyte for fertilisation
Middle piece contains mitochondria = lots of ATP to keep tail moving for long journey
Principal and end pieces enable motility: can have defects
111
GnRH stimulates production of LH by … and … by gonadotroph cells in the anterior pituitary
LH stimulates … secretion from Leydig cells relatively quickly
FSH and testosterone stimulate … production which keeps concentration of Testosterone high in testes, FSH = slower
FSH stimulates release of … by Sertoli cells
Testosterone negatively regulates … cell production of …
Testosterone decreases the release of … from the …
Inhibin negatively regulates gonadotroph cell production of …
Leydig cells
FSH
Testosterone
Androgen binding hormone
Inhibin
Gonadotroph
LH
Hypothalamus
GnRH
FSH and LH (therefore not much spermarogenesis would happen as not enough LH or FSH)
112
What do the ovaries produce? And what hormones do they produce?
Secondary oocytes
Hormones: progesterone, oestrogen, relaxin, inhibin (male as well!)
113
What are ovarian hormones?
Steroid hormones - synthesised from cholesterol mainly or Acetyl CoA
Act through nuclear hormone receptors
Oestrogens: only secreted by the ovaries in NON pregnant females.
Potency= b estradiol > estrone > estriol (least potent)
Progestins: progesterone is the most important
Only secreted by corpus luteum in NON pregnant females
114
Path of sperm cell:
Corona radiata - zona pellucida - plasma membrane of secondary oocyte - cytoplasm of secondary oocyte
115
Describe fertilisation
Most likely to occur when sex takes place between 2 days before ovulation to 1 day after
Usually in the Fallopian tube 12-24hr after ovulation
Capacitation of sperm occurs several hours after sex: tail bears more vigorously, removal of cholesterol, proteins and glycoproteins from the head = easy release of enzymes in the acrosome upon penetration
116
What are the steps involved in the movement of a fertilised embryo?
1. Fertilisation
2. Cleavage
3. Morula
4. Blastocyst
5. Implantation
117
How is labour controlled?
Progesterone inhibits contractions during pregnancy
Placenta secretes cortciotropin releasing hormone which stimulates anterior pituitary gland of foetus to secrete ACTH = production of an intermediate that can be converted to oestrogen. Causes a sharp oestrogen increase, overcoming progesterone effects as progesterone is suppressing birth
Increase in oestrogen increases oxytocin receptors on uterine muscle cells
Oxytocin causes uterine contractions abs relaxin release
118
What is growth hormone and what is its effects?
It is a somatotrope - secreted by somatotroph cells of anterior pituitary
2 main effects: stimulates tissue growth and influences metabolism
119
What is human growth hormone hGH and what does it stimulate?
Peptide hormone of 191 amino acids. It keeps the brain functioning
Signals by binding to tyrosine kinase receptors on outside of cells
Stimulates: body growth - increase in cell size and rate of mitosis, increasing proliferation
Secretion of IGF1
Lipid breakdown
Counteracts actions of insulin (in fasted state, prevents uptake of glucose!)
120
GH receptor signalling:
Serine kinases phosphorylate proteins on a serine residue
There is stimulation from the cell membrane though binding of receptor - activates a kinase cascade which allows proteins to change shape and then be imported into nucleus
This can then induce transcription
121
What are the effect of growth hormone?
And what are the effects on bone?
Increase tissue size by increasing protein synthesis, RNA and DNA synthesis and increasing mitosis
In liver stimulates IGF1 production
Bone: increased protein deposition by chondrocytes and osteogenic cells
Differentiation of osteogenic cells into osteoblasts (blast = build l!) (stimulates the increase in bone length by increasing calcium deposition)!
122
What are insulin like growth factors?
(Work with growth hormone to ensure bone growth)
Peptide hormone growth factors, act via a G protein coupled receptor signalling (via adenyl Cyclase and cAMP)
2 related factors IGF1 and IGF2
Synthesised in growing tissues eg bone, adipose and liver
123
Functions of IGFs? And in the bone?
IGF1 is an important part of growth hormone feedback control. Stimulates growth
IGF2 is the most active in embryonic phase of development where it stimulates embryonic growth
Bone: all aspects of chondrocyte function (collagen / bone matrix production)
Formation and maturation of osteoblasts
124
What are the metabolic effects of growth hormone in a FASTED state?
Drives for maintenance of blood glucose levels:
Adipose and muscle - decreases glucose uptake
Liver and adipose - drives glucogenesis, gluconeogenesis (liver) and lip Iipolysis (adipose)
125
What causes growth hormone GH release?
It is regulated based on physiological state:
Is a stress hormone - it increases with neurogenic or physiological stress (exercise)
Acute hypoglycaemia (low blood glucose levels) is a trigger for the release of GH
Increase in AA in the blood stimulates GH release
Increase blood glucose concentration and increase in free fatty acids leads to inhibition of GH release
126
What happens if GH goes wrong?
Pituitary dwarfism
GH deficiency in children. Not life threatening
Slow bone growth, but fairly normal body proportions
If untreated maximum height = 4 feet
May be associated with deficiencies in other pituitary hormones eg TSH, gonadrotrophins
Treatment with GH treatment - must be human GH
127
High levels of GH = pituitary gigantism
hGH hypersecretion in children
Rapid bone growth but fairly normal body proportions
May reach 8 feet tall
Rare clinically
128
What is acromegaly?
Increased hGH secretion during adulthood
Enlargement / thickening of hands, feet, jaw and face
Thickening of some soft tissues eg facial features
Surgical treatment
129
What are secondary female sec characteristics?
Mainly due to oestrogens which are only expressed at high levels from puberty onwards
Cell growth: increase size of ovaries, Fallopian tubes, uterus and vagina
Development of stromal tissue and deposition of fat in the breasts
Increase in body metabolism and fat deposition
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What is Menopause?
40-50 years of age sexual cycle becomes irregular then ceases
Few primordial follicles remaining and production of oestrogens decrease
At low enough concentration oestrogens cannot inhibit production of LH and FSH (gonadotropins)
Loss of oestrogens = hot flushes , irritability, fatigue, decreased strength and calcification of bones
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What is Hypoglycemia?
Decreased blood levels of fatty acids
Increased blood levels of amino acids
Sympathetic activity
Deep sleep
Testosterone, estrogens, thyroid hormones and ghrelin
Inhibits release of GHRH from hypothalamus
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What is hyperglycaemia?
Increased blood levels of fatty acids
Decreased blood levels of amino acids
Obesity
Ageing
High blood levels of GH and IGFs
Inhibits release of GHIH from hypothalamus
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Where is calcium present?
99% in bone as calcium phosphate (hydroxyapatites - form surface of bone)
Other 1% present in:
Intracellular free calcium
Extracellular fluid (0.1% total calcium)
Most is in blood:
Combined with plasma proteins which cannot diffuse across basement membrane - 41%
Free in blood combined with anions K+, PO4-, citrate etc, can diffuse out across basement membrane - 9%
Present as an ion within blood, can diffuse across basement membrane - 50%
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What is hypercalcemia?
High Ca2+
135
What is hypocalcemia?
Low Ca2+
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99% calcium in the body is stored in … or …
Dietary calcium enters the … and is taken up into the extracellular fluid ECF which works as a … ‘bucket’ that other areas can dip into
MAIN MECHANISM THAT EXTRACELLULAR CALCIUM LEVELS CHANGE IS THROUGH BONE REMODELLING:
Bone … takes calcium from ECF and stores it as … crystals
Bone … uses hydroxyapatite crystals, degrades them to release … which is returned to the …
Other mechanisms include: reabsorption from the filtrate in the …
Teeth, bone
GI tract
Central
Deposition
Hydroxyapatite
Resorption
Calcium
ECF
Kidney nephron
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What is parathyroid hormone secreted by?
The chief cells of the parathyroid gland
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What is vitamin D and what is its sources?
Vitamin D is a steroid hormone
Sources:
diet as vitamin D2 and D3, then metabolised further by liver and kidney
Synthesis from 7-dehydrocholesterol in the keratinocytes of the skin, stimulated by sunlight and heat
PTH stimulates production of calcitriol in the kidney. <12ng/ml indicates vitamin D deficiency
139
What happens when calcitriol binds vitamin D receptor?
Increases expression proteins involved in calcium transport mechanisms in the intestine - increasing uptake from the diet
140
What is Calcitonin?
Short peptide hormone 32AA - secreted by parafollicular cells of thyroid gland when calcium concentration in extracellular fluid is high
Stimulates osteoblasts, makes bones stronger
Opposes PTH
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What is Calcitonin?
Main aim of it is to decrease plasma calcium concentration by:
Preventing bone resorption by inhibiting the activity of osteoclasts (clast = collapse), shift towards bone deposition
Decrease in production of new osteoclasts - fewer the number, less action = reduction in resorption of calcium
Accelerates uptake of calcium from ECF
May increase renal calcium excretion
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PTH disorders - what is hyperparathyroidism?
Commonly caused by a tumour (adenoma of parathyroid). Results in hypercalcaemia
Increase in renal excretion but hypercalcaemia results in increase calcium filtration via kidneys = kidneys stones and possibly death
Skeletal effects: increased bone turnover, bone loss, demineralisation common = fractures and pain
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PRH disorders - what is hypoparathyriodism?
Usually caused by damage / failure / removal of parathyroids
Decreased level of PTH = inability to maintain calcium and phosphate homeostasis = hypocalcemia and hyperphosphatemia
Decrease in renal calcium resorption = hypercalciuria which exacerbates need for greater calcium intake from diet and calcitriol increases
Symptoms: tetany (involuntary muscle contraction), renal malfunction, cardiac manifestations
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Examples of vitamin D deficiency in children and adults:
Children: rickets - skeletal deformity eg bow legs
Adults: osteomalacia - decrease in bone density which could increase risk of fractures and pain
MS
CVD
Type 2 diabetes
Sepsis
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What are the effects of growth hormone on bone?
Overall growth of long bones at epiphyseal cartilage by:
Deposition of new cartilage = conversion to bone
Osteoblasts in bone periosteum and bone cavity deposit new bone on top of older bone
When Deposition is > resorption = thickening!
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How can IGF1 and hGH lead to osteoporosis?
IGF1 enhances the balance between deposition and resorption, therefore deficiency leads to reduced deposition of bone = decreased bone thickness
Use of hGH as a drug has potential anabolic effects all over the body and may stimulate greater exercise = enhance bone turnover
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Menopause:
Osteoporosis causes by loss of oestrogens due to…
Increase osteoclast activity and decreased osteoblast activity, resorption > deposition = DECREASES thickness (demineralisation)
Decrease in bone matrix
Greater incidence of bone fracture
Can be overcome with hormone replacement
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What does the thyroid gland secrete?
Thyroxine T4, tri iodothyronine T3 and calcitonin
T3 and T4: iodine containing hormones acting throughout the body. Regulate metabolism and body temp
Calcitonin: regulates plasma calcium
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For the synthesis of thyroid hormones T3/T4, two components are necessary…
Thyroglobulin and iodine
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What Is thyroglobulin?
670kDa glycoprotein
Comprises 2 peptides of 330kDa and carbohydrate moieties
Synthesised in follicular cell Rough ER
Packaged into vesicles and released into lumen by exocytosis
Stored as colloid (main source of iodine) - known as organification
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What is iodination?
T3 and T4 require dietary iodine - 75mg/day
Iodide trapping = inorganic iodide enters follicular cells via Na / I symporter NIS
iodine transported > follicle lumen
Iodination of free tyrosine residues of thyroglobulin
Hydrolysis of iodinated thyroglobulin = T3 and T4
Some T3 synthesised BUT approx 20-fold more T4!!
Thyroid stores several weeks supply of T3 and T4
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Thyrotrophin releasing hormone TRH stimulates thyroid stimulating hormone TSH release from anterior pituitary
What do thyroid hormones do?
Promote oxidative metabolism, influence metabolism which is necessary for full expression of growth hormone in children = SYSTEMIC METABOLIC EFFECTS
LOTS of TSH > lots of T3 and T4 release > causes -ve feedback > decrease in TSH levels
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SECRETION OF THYROID HORMONES:
Colloid droplets taken up by follicle cells by…
Lysosome fuses with colloid droplets. Thyroglobulin … and degradation products …
Released T3 and T4 hormones diffuse into … surrounding follicles. (T3 is released to be active at intra cellular receptors due to LOW half life)
In blood, hormones bind to plasma proteins > are lipophilic > need carrier protein
Mostly thyronine binding protein TBP = carrier protein
Some prealbumin TBPA and …
T4 binds with increased affinity = increased half life!
Endocytosis
Degrades
Recycled
Fenestrated capillaries
Albumin
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Roles of TSH in thyroid function:
(Thyroperoxidase enzyme)
G protein coupled receptors GPCR coupled to adenylate cyclase (makes cyclic AMP)
Stimulation of hormone synthesis by TSH binding- iodide trapping via Na/I co transporter = More NIS
Increased thyroglobulin synthesis (TSH binding > large amounts cAMP> protein kinase A turned on > endocytosis of thyroglobulin stimulated)
Increase iodination of thyroglobulin = more iodine storage in colloid
Stimulation of hormone secretion- increase uptake of colloid by follicular cells
Necessary for thyroid gland maintenance - gland rapidly atrophies in absence of TSH!
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What are the actions of thyroid hormones T3 and T4?
T3 has far greater activity than T4. Intracellular conversion of T4 to T3 by deiodlinase 2
Act as growth factors in multiple tissues (so thyroid key for child growth)
Regulate gene transcription
Induce specific tissue effects: altered protein metabolism, increase BMR, activity of Na+ / K+ ATPase (important to maintain intracellular potassium levels = helps maintain membrane potential)
Increase glucose uptake and lipolysis (fat breakdown)
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Abnormal thyroid function diseases
Hyperthyroidism - overactivity
Graves’ disease: autoimmune. Symptoms include goitre, increase BMR, heart rate and weight loss
Hypothyroidism:
Eg Myxedema in adults and cretinism in children
Causes: iodine deficiency > decreased thyroglobulin > decreased T3 and T4 > increased TSH > goitre
Hashimoto’s thyroiditis > thyroid destruction
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The exocrine vs endocrine pancreas
Exocrine activity = secretion via a specialised duct to epithelial surface
It aids digestion via secretion to duodenum - contains bicarbonate and rich in digestive / lytic enzymes
85% pancreatic volume = exocrine function
Endocrine activity = secretion directly into the blood WITHOUT a duct
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What are the islets of langerhaans?
What is the morphology of endocrine cells?
Major endocrine cells!
a= glucagon
b= insulin
&= somatostatin
RER / Golgi complex
Secretory granules
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What are the physiological effects of insulin?
An anabolic hormone - stimulates production of glycogen, lipid and protein
Binds to plasma membrane receptor (linked to tyrosine kinase)
Increased cellular uptake of glucose (stimulates GLUT4)
Increased cellular uptake of amino acids
Muscle: glucose > glycogen and amino acids > protein
Liver: glucose > glycogen and triglycerides
Adipose: glucose > triglycerides
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What is glucagon?
Peptide hormone (a cells)
Mainly increases catabolism (liver)
Acts in opposition to insulin! Stimulates glycogenolysis, maintains fasting blood glucose and mobilises triglycerides from adipose tissue
Acs via GPCRs and cAMP signalling
Regulation of glucagon production - hypoglycaemia causes increased glucagon
161
What is somatostatin?
(An example of how the SAME signalling molecule can be made and used by different parts of the body and have DIFFERENT physiological function in each of those parts of body!)
Peptide hormone (& cells)
Inhibits insulin and glucagon secretion (paracrine mechanism)
Secreted after meal and increase duodenal acid
At high concentrations, it inhibits virtually ALL gastrointestinal functions
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The adrenal cortex:
(Approx 75% of adrenals)
3 subregions that secrete different steroid hormones
Zona glomerulosa = mineralocorticoids
Zona fasciculata = glucocorticoids
Zona reticularis = sex steroids
ESSENTIAL FOR LIFE: if we don’t have aldosterone (mineralcorticoids) kidneys won’t function. If we don’t have sodium (mineralcorticoids) cells can’t function! Cortisol (glucocorticoids) is essential for body to function!
163
General properties of steroid hormones
Synthesised from cholesterol
Little storage in endocrine cells - de novo synthesis
Mostly transported bound to plasma proteins > to be soluble in aqueous solutions
Are lipophilic so diffuse across cell membrane into blood
Slow, long term actions (regulation of transcription)
164
Disorders of cortisol secretion: Cushing’s syndrome and Addison’s disease:
Cushing’s syndrome: increased plasma cortisol due to adrenal tumour, increased ACTH secretion etc
Symptoms: diabetes mellitus, susceptibility to infection, muscle wasting
Facial and trunk obesity (Mellon on toothpicks)
Addison’s disease: decrease in function of adrenal cortex caused by damage to adrenal or pituitary gland = decrease in cortisol concentration. Autoimmune disease
Symptoms: hypoglycaemia, lethargy, weight loss
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The adrenal medulla:
Primary cell type = chromaffin cells
(Considered as specialised sympathetic post ganglionic neurones)
Contain sympathomimetic catecholamines:
Adrenaline 80% and noradrenaline 20%
Derived from tyrosine via dopamine
Stored in vesicles as are NOT steroid hormones
Released via exocytosis
Functional importance in sympathetic fight or flight response to acute stress!
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Action of adrenal medullary catecholamines + effects of adrenaline
Rapid, transient effect compared to steroids. Short half life = few mins
Act via plasma membrane adrenoceptors
Multiple receptor types allow tissue specificity of effect
Effects of adrenaline: increase heart rate, oxygen consumption and skeletal muscle blood flow. Breakdown of glycogen and fat
167
Disorders of adrenal medulla function:
Pheochromocytoma: tumour of chromaffin cells = increased catecholamine output
Severe hypertension
Hyperglycaemia
Increased metabolic rate
Arrhymias
Anxiety
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Mineralcorticoids eg aldosterone:
Regulate homeostatic control of minerals (Na+, K+, H+)
Primary mineralcorticoids = alderterone
Part of renin-aldosterone system RAAS
Stimulated by increased angiotensin II
Essential for Na+ maintenance!
In plasma mostly bound to albumin
169
A 28 year old woman from east Africa was admitted to hospital with suspected aplastic anaemia. Her test results were:
Ca2+ concentration = 1.96mmol/L
[albumin]serum = 37g/l (normal is 38-48)
Alkaline phosphatase = 1238 IU/I (normal is 30-120)
Serum 25-hydroxy vitamin D conc of 6nmol/l (normal is 20-100)
What was wrong with the patient and why?
Osteomalacia (loss of bone mineralisation, only in adults!) (rickets for children) due to vitamin D deficiency. What are the causes of vitamin D deficiency?
Shifting towards bone resorption rather than deposition.
In the UK (with substantially less sun than East Africa) lack of sun exposure and poor dietary intake leads to much higher prevalence in high risk populations including African and Asian pops and the elderly!
170
What would happen if a gallstone was to block the hepatic duct or common bile duct?
If you had a gallstone you wouldn’t be able to secrete bile from the hepatocytes because the way out of blocked
Bile would normally go from hepatocytes into bile caniculli directly than filters out through portal triad into hepatic duct
BUT if common hepatic duct is blocked then bile will fill up route out and so we can’t secret bile! Hepatocytes will start malfunctioning and will have build up of some primary bile acids = super reactive / toxic.
So will end up with intra hepatic hepatitis = malfunctioning of hepatocytes in liver
If gall stone blocked common bile duct = extra hepatic jaundice
171
What is the physiological importance of the endocrine system?
Controls many aspects of physiology via secretion of hormones
Endocrine and neuronal systems are the 2 major control systems
Endocrine systems also interact with cardiovascular, digestive and immune systems
172
What is a hormone?
Defined as a chemical messenger secreted into blood to act on distant targets
Present at very low concentrations in the body due to highly specific mechanisms of action in target tissues
173
What are the 3 main groups of hormones?
Amino acid derivatives - tryptophan (melatonin), tyrosine (eg adrenaline)
Peptides - TRH, growth hormone
Steroids
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What are the 4 groups of hormonal regulation?
Reproduction - eg FSH, sec steroids
Energy balance - eg insulin, thyroid hormones, leptin, orexin, ghrelin
Growth and development - eg growth hormone, thyroid hormone, sex steroids
Homeostasis - eg vasopressin, aldosterone
Other roles: biological rhythms
Variable time course of hormone action: seconds / minutes =adrenaline
Hours / days = steroids, thyroid hormones
175
Anatomy of the endocrine system:
Endocrine glands: ductless glands that secrete hormones into the blood
Pancreas acts as BOTH an endocrine and exocrine gland
176
Other important endocrine organs
Pineal gland - secretes melatonin, important for biological rhythms
Adipose tissue (fat) and GI tract - secrete many hormones involved in energy balance and metabolism
Placenta - secretes hormones involved in foetal and maternal development
177
What does heterogeneity and homogeneity mean?
Heterogeneity - amount of variation within a subject
Homogeneity - uniformity of a subject
178
If hormones cause changes in physiology how do they do this?
They bind to receptors on target cells
Receptors may be located at different concentrations in different parts of the body
Receptor concentrations dictate the strength of the reaction to the hormone:
High receptor concentration = big reaction
Low = small reaction
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What are the effects of hormone receptor binding?
Change in transporter activity
Activation of secondary messengers (signalling cascade)
Effects are long acting (hours, days) because hormones influence protein synthesis through gene expression
180
What are the amine hormones?
Adrenal amines (adrenaline and noradrenaline)
Synthesised from tyrosine and stored in cytoplasmic vesicles
Thyroid amines (T3 and T4)
Synthesised via a multi component pathway involving protein thyroglobulin Tg
Stored as a large precursor called colloid
181
To become fully functional proteins may require further processing after translation.
What modifications are peptide hormones subject to?
Preprohormones:
Inactive precursor from a single gene
Cleaved > active components
Eg POMC
Dimerisation
Subunits from different genes
Combine > active product
eg LH, FSH, TSH
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How are thyroid amines and steroid hormones secreted?
They are both lipophilic
Diffuse across cell membrane into blood so NO active secretory mechanism
Once in blood transported bound to plasma protein
Steroids released immediately after de novo synthesis
Thyroid hormones are only released after they dissociate from colloid precursor
183
Secretion of adrenal amine and peptide hormones is via…
Exocytosis
184
Membrane bound receptors (for hydrophilic peptide and amine hormones):
Binding of hormone (first messenger) to its … activates it
Activated adenylate Cyclase eg converts ATP to …
Activated protein kinases …cellular proteins
Millions of phosphorylated proteins cause reactions that produce … responses
Receptor
cAMP
Phosphorylate
Physiological
Typically responses are rapid and cause a change in membrane permeability and / or enzyme activity
185
Intracellular receptors (for steroid and thyroid hormones). They stimulate gene expression > delayed and prolonged response
Lipid soluble hormone diffuses into cell
Activated receptor hormone complex alters …
Newly formed … directs synthesis of specific proteins on …
Gene expression
mRNA
Ribosomes
186
What are the posterior pituitary hormones?
Oxytocin - released during parturition
Required for milk ejection in lactating mammary glands
Arginine vasopressin AVP - aka antidiuretic hormone ADH
secreted in response to increased blood osmolarity
Increases water absorption in kidneys
187
The LH Surge - Positive Feedback Loops:
Oestrogen usually inhibits LH secretion via …
BUT oestrogen surge occurs around day … of the cycle
… oestrogen drives change from -ve to …feedback
+ve feedback causes LH surge which induces …
After ovulation, drop in oestrogen conc causes resumption of … and thus LH / FSH secretion falls!
Negative feedback
12
High
+ve
Ovulation
-ve feedback
188
What BEST describes steroid hormones?
They can bind to blood carrier proteins and act via intracellular receptors
189
What hormone would be unaffected by an obstruction of the hypophyseal portal circulation?
Oxytocin
190
Which hormone requires exocytosis for its secretion?
Gonadotrophin releasing hormone (GnRH)
191
At what stage of T3/ T4 synthesis and secretion is exocytosis most important?
Release of thyroglobulin into the follicle lumen
192
Which hormones act to elevate plasma glucose concentrations?
Cortisol
Growth hormone (GH)
Glucagon
193
What would give a doctor info on the functionality of the liver?
Albumin and clotting time
194
How are the sinusoids structurally adapted for their function?
It has a highly permeable barrier that enables rapid exchange between blood and cells and eventually bile
195
Give the order of events that occur AFTER consuming a large high fat cheeseburger
1. Cholecystokinin CCK is released
2. Vagal and enteric nerves fire
3. CCK stimulates bile reconstitution and contraction of the gallbladder
4. The sphincter of Oddi is relaxed + opens
5. Stomach is now EMPTY so Secretin is released
196
What is INCORRECT regarding growth hormone?
Growth hormone stimulates glucose transport into cells
197
What would contribute to the development of osteoporosis?
(Anything that shifts more to bone resorption)
Removal of female reproductive tract (hysterectomy)
Deficiency of calcitriol - low calcium would be coming in
Growth hormone receptor mutation - shift towards resorption
Over production of parathyroid hormone PTH - it drives the resorption of bone!
198
What would be observed when calcium levels are low?
The balance between bone deposition and resorption shifts to favour resorption!
