Endocrinology Flashcards
(258 cards)
1
Q
what is the homeostasis
A
Maintenance of a stable internal environment necessary for normal body functioning
2
Q
is Stable ≠ static
A
Stable ≠ static
State of dynamic equilibrium
BALANCE of everyday physiological
processes
3
Q
how is homeostasis in the internal enviornment
A
Our internal environment remains remarkably
consistent despite changes in the external
environment
4
Q
does specialized organs allow moving the chemicals from the external enviornment to the internal enviornment in the body
A
Specialized organ systems allow movement
of chemicals from the external to the internal
or vice versa
5
Q
what does homeostatic mechanism provide
A
• Homeostatic mechanisms provide the stable
conditions necessary for cell function
6
Q
what fetures helps organs to mentain the homeostasis
A
Every organ in your body helps to maintain homeostasis through neural and/or hormonal mechanisms
7
Q
what are the enviornmental changes controlled by
A
- Constant monitoring of the composition of blood (multiple sensory systems)
- Responding to changes in blood composition (multiple response systems)
- Most response systems operate in a negative feedback manner
8
Q
what are the two factors in the enviornmental changes
A
Neurotransmitters + Hormones
9
Q
body is the communication between …… and ……..
A
The body’s means of communication between cells and tissues
10
Q
what is the homeostasis control mechanism
A
• SENSOR: Responsible for constant monitoring
• INTEGRATOR: Coordination of response(s)
• EFFECTOR: Response to effect change in
variable(s)
11
Q
what are the sensor, integrator and affector in lyding»_space;»>stanging up
A
blood pressure falls: simulator blood pressure receptor responed: sensor brain: integrator center heart rate increase: affector 4. rise blood pressure : affect
12
Q
what is the 10th leading death in canada
A
Mellitus diabets
13
Q
how many of the canadians have the thyroid disorders
A
1 in the 10 canadians
14
Q
what are the distruption of the homeostasis that cause the disease in the body
A
Overproduction: Hypersecretion Underproduction: Hyposecretion Hormone resistance Transport or clearance problems Hormone resistance
15
Q
what is the endocrine physiology
A
Endocrine Physiology
The study of hormones and their actions
The study of how endocrine glands regulate
the physiology and behaviour of animals
16
Q
what is the endocrine glands
A
Endocrine Glands
Any tissue which releases (secretes)
hormones into the bloodstream to effect
change in another tissue
17
Q
what is the dicovery of pancreas involved in
A
Discovery of pancreas involvement in
diabetes
18
Q
how Discovery of pancreas involvement in
diabetes
A
1.Surgically remove pancreas => dog
develops symptoms of diabetes
2. Implant pieces of pancreas under skin =>
prevents symptoms of diabetes
19
Q
how the insulin is descovred
A
Discovery of insulin
(Banting and Best, 1921)
1. Identified anti-diabetic substance in
pancreatic extracts
2. Injected extracts prevented symptoms of
diabetes (prevents elevated blood
glucose)
20
Q
how is the affect of the affect of the molecules secregation on the endocrine glands
A
Molecules secreted by endocrine
glands (organs) into the extracellular
the fluid that exerts their effects on the target
tissues some distance away
21
Q
what are the level of the effcet
A
autocrine: secretory cell and the target cell are in the same tissue
paracrine: secretory cells affect target cells and other nearest tissue
endocrine : secretory cell segregate hormone in the blood stream and it goes through the target tissue via the circulatory system
22
Q
what are the classes of the hormons
A
Amines
Peptides
Proteins
Steroids
23
Q
what are the amins hormones
A
Norepinephrine
Epinephrine
Thyroxine
Melatonin
24
Q
what are the peptid hormones
A
Hypothalamic
hormones
Insulin
25
what are the protein hormones
Growth hormone
| Prolactin
26
what are the stroids hormones
Glucocorticoids
Mineralocorticoids
Gonadal steroids
27
what is the synthesis , storage , release from cell, transport in blood , half life, and example of the peptides/ proteins
```
Synthesis> In advance
Storage >Secretory vesicles
Release from cell >Exocytosis
Release from cell > Exocytosis
Half life> Short
Example> Insulin
```
28
what is the synthesis , storage , release from cell, transport in blood , half life, and example of the Steroids
```
Synthesis > On demand
Storage > --
Release
from cell >Diffusion
Transport in blood> Bound to carrier proteins
Half life>Long
Example >Estrogen
```
29
what is the synthesis , storage , release from cell, transport in blood , half life, and example of the Amines
(Catecholamines)
```
Synthesis>In advance
Synthesis > In advance
Release from cell> Exocytosis
Transport in blood> Dissolved in plasma
Half life > Short
Example > Epinephrine
```
30
what is the synthesis , storage , release from cell, transport in blood , half life, and example of the Amines
(Thyroid)
```
Synthesis >In advance
Storage > Secretory vesicles
Release from cell > Diffusion
Transport in blood> >Bound to carrier proteins
Half-life > Long
Example > Thyroxine
```
31
how hormones binf tot the receptors in the target cell
Hormones bind non-covalently to
| receptors in/on target cells
32
where are the receptors for most hormones
• The receptors for most hormones
are found in the plasma membrane
of target cells
33
where are the receptors for steroid and thyroid hormones
• The receptors for steroid and
thyroid hormones are found in the
cytoplasm/nucleus of the target
cells
34
are receptor very high specificly
```
Receptors have very high
specificity for a particular
hormone (e.g., insulin receptors
usually only bind insulin), but some
non-specific binding does occur
```
35
• There is continuous turnover of
the receptor-hormone complex
(essential for any signaling system
• There is continuous turnover of
the receptor-hormone complex
(essential for any signaling system
36
what kind of the hormone receptor do we have in the body
transmembrane receptor >> most hormones
cytoplasm ( majority )
nucleus( thyroid hormone recptor )
37
how does the Transmembrane receptor works
Use second messenger systems
38
what are the second Transmembrane receptor types
G-protein linked receptors
| Tyrosine kinase receptors Cytokine receptors
39
what are the two types of the G-protein linked receptors
Two types:
Adenylate cyclase-cAMP
Phospholipase C-Ca2+
40
how does G-protein linked receptors work
Downstream effects promote
phosphorylation + activation of enzymes responsible
for carrying out hormone’s effect
41
how does Tyrosine kinase receptors
| Cytokine receptors work
Directly phosphorylate + activate enzymes responsible for carrying out hormone’s effect
42
which hormones use the second messenger
All hormones EXCEPT for steroid/thyroid hormones use 2nd messenger systems
43
what are the examples for the Adenylate cyclase-cAMP 2nd messenger system
Example: Norepinephrine + epinephrine
| (catecholamines) beta adrenergic receptors
44
what are the Adenylate cyclase-cAMP 2nd messenger system steps
Steps:
1. Hormone binds to receptor
2. Alpha subunit dissociates from G proteins
3. Alpha subunit activates adenylate cyclase
4. cAMP is formed
5. cAMP activates protein kinase
6. Protein kinase phosphorylates various
enzymes in the cell
45
what are the Phospholipase C-Ca2+ 2nd messenger system examples
Example: Norepinephrine + epinephrine (catecholamines) alpha 1 adrenergic receptors
46
what are the Phospholipase C-Ca2+ 2nd messenger system steps
Steps:
1. Hormone binds to receptor
2. Alpha subunit dissociates from G proteins
3. Alpha subunit activates phospholipase C
4. DAG and IP3 is formed
5. IP3 enters endoplasmic reticulum
6. Stored Ca2+ diffuses into cytoplasm
47
explain the insulin receptor
1. two half receptors form dimer prior to insulin binding
2. insulin binding causes autophosphorylation of receptor
3. activate tyrosine kinase of receptor phosphorylate insulin receptor substrate
4. activate signaling molecule causes cascade of the effect
5. glucose uptake and anabolic reaction
48
what are the Cytokine 2nd messenger system examples
Example: Growth hormone receptor
49
what are the Cytokine 2nd messenger system steps
Steps:
1. Hormone binds to receptor
2. JAKs are activated
3. Activated JAK proteins then phosphorylate
STAT proteins
4. Activated STAT proteins translocate to
nucleus to influence gene expression
50
what is the Nuclear hormone receptors example
Example:
| Thyroid hormones
51
what is the Steroid hormones's receptors steps
```
Steps:
1. Steroid hormone transported bound to
a plasma carrier protein
2. Steroid hormone binds to a receptor in
the cytoplasm
3. Translocates to the nucleus, binds to DNA (acts
as a transcription factor)
4. Stimulates gene transcription
5. Protein products
6. Hormone response
```
52
what are the Thyroid hormones Steps:
```
Example: Thyroid hormones
Steps:
1. Thyroxine hormone (T4) usually bound to
carrier protein
2. T4 is converted into T3 (triiodothyroxine)
3. T3 enters nucleus
4. Hormone-receptor complex binds DNA
5. New mRNA
6. Protein synthesis
7. Hormone response
```
53
what is the role of the hormones in the changes in tissues
To enact change in tissues, many hormones are controlled via negative feedback mechanisms through hormone producing structures
54
what are the hormone producing structures:
1. Endocrine organs within the hypothalamus-pituitary glandtarget cell (HPTC) axes
2. Endocrine cell groups/zones/layers
• E.g. pancreatic islets, adrenal medulla
3. Dispersed endocrine cells
• E.g. gut hormones, thyroid parafollicular cells
55
what are the The biological relevance of HPTC axes
Links the endocrine system to the environment via the brain Step-wise increase in signal from
hypothalamus => pituitary gland => peripheral target tissues
Adjustments can be made at several different levels of each axis
56
HPTC axeis connect two things
Links the endocrine system to the environment via the brain
57
what does HPTC step-wise increase
Step-wise increase in signal from hypothalamus => pituitary gland => peripheral target tissues
58
can adjustment make at the HPTC
Adjustments can be made at several different levels of each axis
59
what does anterior pituitary control in the body
endocrine glands
60
what does posterior piturity control in the body
extension of neural tissues
61
what is the Hypothalamus and Pituitary Gland protected by
protected by bone
62
what are the two system that hypothalamus is master of
Hypothalamus is the master
controller of lower autonomic
functions AND the endocrine system
63
hypothalamus produce and secretes hormones into ......... and .......... lobe of the pituitary glands
Produces and secretes hormones
into the anterior and posterior lobe
of the pituitary gland
64
when does the hypothalamus produce or secrete hormones
Receives feedback from target
tissues to promote or inhibit
hormone production/release
65
what is the Pars distalis
Pars distalis: anterior lobe (endocrine part of pituitary gland)
66
what is the Pars tuberali
Pars tuberalis: wraps around
| infundibulum
67
what is the Infundibulum
Infundibulum: funnel-shaped
| structure
68
what is the Posterior lobe:
```
Posterior lobe: neural part of the
pituitary gland (pars nervosa)
```
69
what is the action of the ADH/ oxytocin with the axonal
Axonal projections from neurosecretory cells of the hypothalamus supply pars nervosa with ADH/oxytocin
70
what are the Supraoptic nucleus neurosecretory
| cells
Supraoptic nucleus neurosecretory
| cells: ADH/oxytocin
71
what is the Paraventricular nucleus
| neurosecretory cells
Paraventricular nucleus
neurosecretory cells:
Other hypothalamic hormones
72
what does Paraventricular nucleus neurosecretory cells do
These cells produce hypothalamic hormones
that are secreted into blood capillaries to
reach the anterior pituitary
73
what are the Importance of the anterior lobe
```
Function of target glands is dependent
upon adequate stimulation by anterior
pituitary (AP) hormones
Hypothalamic hormones are secreted
into the portal venules that bring them
to the AP
Endocrine cells respond to hypothalamic
hormones and secrete OR inhibit
release of AP hormones
```
74
function of the target glands is depends upon what ??
Function of target glands is dependent
upon adequate stimulation by anterior
pituitary (AP) hormones
75
Importance of the anterior lobe
```
Function of target glands is dependent
upon adequate stimulation by anterior
pituitary (AP) hormones
Hypothalamic hormones are secreted
into the portal venules that bring them
to the AP
Endocrine cells respond to hypothalamic
hormones and secrete OR inhibit
release of AP hormones
```
76
what are the hormones of the hypothalamus
dopamine (PIH) inhibits secretion of prolactin
PRH ( prolactin-releasing hormones ) Stimulates the release of prolactin TARGET THE MAMMARY GLANDS
thyrotropin-releasing hormone ( TRH) Regulates the secretion of thyroid-stimulating
hormone (TSH) thyroid
Corticotropin-releasing hormone (CRH) Regulates secretion of adrenocorticotropic hormone (ACTH) & melanocyte-stimulating hormone (MSH) Adrenal cortex & skin and hair
Somatostatin (growth
hormone inhibiting hormone; GHIH) Inhibits secretion of growth hormone (GH) Growth hormone releasing hormone (GHRH) Stimulates secretion of GH target cells >>>Many (liver, muscle, bone, etc.)
Gonadotropin-releasing hormone (GnRH) Regulates secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) target gland/tissue is Gonads
Antidiuretic hormone (ADH) released by posterior pituitary) target tissue /cell >>>> Kidney
77
what is the CRH
CRH (Corticotropin releasing hormone)
Peptide hormone, G-protein-coupled
receptor (cAMP) on cells in anterior
pituitary
78
what is the ACTH
ACTH (Adrenocorticotropin hormone)
Peptide hormone, G-protein-coupled
receptor (cAMP) on cells in the adrenal
cortex
79
what is the ACTH
ACTH (Adrenocorticotropin hormone)
Peptide hormone, G-protein-coupled
receptor (cAMP) on cells in the adrenal
cortex
80
how does the CRH produced
CRH synthesis and release
Produced by neurosecretory cells within the
paraventricular nucleus of the hypothalamus
under noradrenergic stimulation
81
how does the CRH released
Released into blood vessels in the
| hypothalamo-pituitary portal system
82
how does the capillaries bring CRH to simulate the G-protein
Capillaries bring CRH to stimulate G-proteincoupled receptors on cells in the anterior pituitary to produce POMC (prohormone)
83
what is the precursor molecule
```
Many hormones are derived from a
precursor molecule (prohormone)
```
84
where does the processing of prohormone > hormone happens
Processing of prohormone => hormone
| usually occurs within the gland cell
85
what are the prehormones
Prehormones: Inactive hormones are
converted after secretion to become
active in their target cells
86
what are some example of the prehormones
Examples of prehormones:
• Vitamin D3 is converted to 1,25-
dihydroxyvitamin D3 in target tissue
87
where does T4 convert to T3
Thyroxine (T4) is converted into triiodothyronine
| (T3) in target tissue
88
what is the Pro-opiomelanocortin:
Pro-opiomelanocortin: A prohormone for many hormones
89
POMC is a precursor of which hormones
POMC is a precursor for ACTH,
| MSH, and other hormones
90
in AP what has happend to the POMC
In the AP, POMC is produced
| and cleaved into ACTH and Blipotropin
91
what is ACTH released by
Active ACTH hormone is released by anterior
| pituitary and travels to adrenal glands
92
what does ACTH binds to
binds to MC2R (melanocortin-2 receptor; Gprotein-coupled)
93
what are the primary and secondery actions of the ACTH
Primary action: Stimulates secretion of
glucocorticoids (cortisol)
Secondary action: Stimulates secretion of sex
steroids
94
what is the adrenal glands
The Adrenal Glands
Paired organs that cap the superior borders of
the kidneys
Consist of an outer cortex and inner medulla
(function as separate endocrine glands)
95
what does medulla produces
Medulla: Produces catecholamines
| epinephrine
96
what is the cotex made of and what are the each layer responsibility
Cortex: A steroid factory (corticosteroids)
1. Zona glomerulosa: mineralocorticoids
(aldosterone) – regulates Na+ and K+ balance
2. Zona fasciculata: glucocorticoids
(cortisol) – regulates glucose balance
3. Zona reticularis: sex steroids (adrenal
androgens) – produced in small amounts
97
what is the starting material for the Steroidogenesis
Starting material: Cholesterol
98
what is common between steroid production
ALL steroid production begins with
the conversion of cholesterol to
pregnenolone
99
how to make cortisol
ACTH (through cAMP) stimulates insertion of StAR protein in the MB StAR protein helps cholesterol move to the inner membrane where it is then converted into pregnenolone Pregnenolone is then converted through a series of steps to become cortisol
100
what is the main glucocorticoid in the animals
Corticosterone is the
main glucocorticoid in
amphibians, reptiles,
rodents, and birds
101
what is the main glucocorticoid in the humans
Cortisol is the main
| glucocorticoid in humans
102
how does cortisol is released
Cortisol Release triggered by:
• Chronic stress (trauma, starvation, exam season, etc.)
• Hypoglycemia
103
what are the immune system of the cortisol
Cortisol
Immune system:
• Decreases cytokine production
• Reduces the production of some immune cells and
cytokines
• Cortisol is a natural immunoregulatory hormone, but
can also be used clinically as an anti-inflammatory
agent
104
what are the glucose metabolism of the cortisol
Glucose metabolism:
• Primary regulator of glucose metabolism during
fasting/starvation
• REDUCES glucose uptake in tissue and
PROMOTES gluconeogenesis and glycogenolysis in
liver
105
see lecture endocrine 2 page 19
106
what cause the Cortisol Excess
Primary hyperadrenocorticism: adrenal tumour causes over-secretion of cortisol (Cushing’s syndrome)
• Secondary hyperadrenocorticism: Pituitary tumour causes over-secretion of ACTH leading to excess cortisol (Cushing’s disease) –MORE COMMON
• Endogenous incidence is rare, but can occur after prolonged exposure to exogenous glucocorticoids
107
how does the cortisol affects the appearence of the body
Cortisol Excess
• Causes changes in metabolism; hyperglycemia;
hypertension; muscular weakness
• Metabolic problems give rise to puffy
appearance, CNS disorders (depression, decreased
learning, memory, etc.)
108
what are the treatments for the hyperglycemia, anti-hypertensive
Treatment:
• Surgery
• Drugs to inhibit steroidogenesis
• Medical management of symptoms (insulin for
hyperglycemia, anti-hypertensives for BP)
• If not treated, overall health can deteriorate;
worsening diabetes, high BP can lead to strokes
or heart attack
109
what cause the cortisal deficiency
Causes:
• Primary hypoadrenocorticism: Destruction of
adrenal cortex causes under-secretion of
adrenal cortex hormones (Addison’s disease)
– MORE COMMON
• Secondary hypoadrenocorticism: Destruction of
pituitary gland causes under-secretion of ACTH
• Treatment for Cushing’s can result in symptoms
of Addison’s disease
110
what is a disorder caused by the cortisol secretion
Primary Hypoadrenocorticism
| Addison’s Disease
111
(Addison’s Disease) diagnosis
```
Diagnosis:
• Weight loss, poor appetite, weakness,
BP changes, hyperpigmentation*,
hypoglycemia, low blood sodium (from
↓ aldosterone)
• ACTH stimulation test
Treatment:
• Steroid preparations (aldosterone &
cortisol analogs)
```
112
how does the skin afftected by the secrecate of the ACTH
*Increased ACTH → POMC → increased MSH (melanocyte stimulating hormone) → more pigment in skin
113
what is the result of the increase in basal metabolic rate
INCREASE basal metabolic rate!
• More ATP production
• More heat production
114
what are the hormones in the thyroid axies
```
TRH: Peptide hormone with a Gprotein coupled receptor (IP3/DAG)
TSH: Protein hormone with Gprotein coupled receptors (both
cAMP & IP3/DAG)
Thyroxine (T4): Amine hormone,
can freely cross the cell membrane
and become T3
Triiodothyronine (T3): Amine
hormone, nuclear receptor
```
115
what is the anathomy of the thyroid gland
Anatomy
Situated below larynx (voice box) on either side of the trachea Two lobes and an isthmus connecting the two sides (prominent isthmus in humans, cows, horses; indistinct in dogs/cats) Largest purely endocrine gland (20-25 g in humans, 10-15 g in dogs)Also home to parathyroid glands
116
where is the thyroid follicles
Thyroid follicles are where T4 (and
| some T3) are produced
117
what is the macroanathomy of the thyroid
Microanatomy
Thyroid follicles are where T4 (and some T3) are produced Follicular cells (thyrocytes) surround thyroid follicles and uptake iodide (I-) from surrounding blood vessels Follicles are filled with colloid, which contains thyroglobulin and enzymes to synthesize T4 and T3 Parafollicular cells dispersed throughout synthesize calcitonin (next lecture)
118
what is the role of the thyrocyets
The role of thyrocytes Iodide (I-) from the blood is transported into the cell by a Na+/I- symport protein Production of thyroglobulin (TG): TSH-mediated gene transcription + protein translation occurs in thyrocytes TG is a long peptide chain with lots of tyrosine side chains on it; once produced it is exocytosed to the lumen (colloid space) Iodide channels pump I- into the colloid space
119
How is thyroid hormone produced? ( first 3 steps )
1. Iodide enters colloid and is converted from iodide to iodine by thyroid peroxidase (TPO)
2. Once oxidized, iodine can bind, one at a time, to tyrosine residues on
thyroglobulin (thanks to TPO)
3. This makes: One iodine + one tyrosine = monoiodotyrosine (MIT; T1)
Two iodines + one tyrosine = diiodotyrosine (DIT; T2)
120
How is thyroid hormone produced? ( second 3 steps )
1. Thyroglobulin brings bound MIT and DIT molecules together
2. Enzymes in the colloid modify the structures of MIT and DIT to make thyroid hormones:
1. T3 (TRIiodothyronine)
2. T4 (TETRAiodothyronine or thyroxine)
3. TSH stimulation induces thyrocytes to take up bound T3 and T4, hydrolyze them from thyroglobulin, and secrete hormone into the blood
121
How is thyroid hormone produced and released?
TSH (released by anterior pituitary) stimulates production of TG and release of free T3/T4 from thyrocytes
122
when the circadian secretion is highst in the humans
Circadian secretion of T3/T4 (highest between
| 10 AM and 2 PM in humans)
123
is T3/T4 secretion higher in younger or older animals
• T3/T4 secretion higher in younger animals
124
T3/T4 secretion higher under which conditions
T3/T4 secretion higher under stress/cold
| conditions
125
what are the effects of the physiological action of thyroid
MAIN EFFECTS:
1) Regulation of metabolic rate (glucose consumption + ATP production in cells) and thermogenesis (heat production)
2) Appropriate levels of thyroid hormone are essential for normal cardiac function
3) Essential for normal fetal development, particularly gonad and CNS development
126
what is the Hypothyroidism
• Hypothyroidism is a condition in which
serum levels of T4/T3 are abnormally
low
127
what are the clinical signs of the Hypothyroidism
Clinical signs: Lethargy, weight gain,
exercise intolerance, cold intolerance
(slowing of metabolic processes)
128
what causes the Hypothyroidism
• Causes: Immune-mediated destruction
of thyroid gland (often); iodide
deficiency in diet
129
secondary or tertiary disease mutant :
Less often: Secondary or tertiary disease,
mutant hormone receptors, mutant transport
proteins
130
what is the Hypothyroidism in developing babies
Cretinism
131
what is the Cretinism
Cretinism: Congenital deficiency of
thyroid hormone production usually due
to maternal hypothyroidism
132
how does the cretinism happens
Lack of thyroid hormones from mother in utero (delivered through the placenta) leads to reduced physical growth AND severe mental disability
133
how does thyroid helps in brain development
Brain development in utero is a complicated
process; thyroid hormone assists with
neuronal maturation, myelin formation, and
dendritic/axonal growth
134
how many people are suffering from the iodine deficiency
approximately 2 billion people
135
what is the Hyperthyroidism
• Hyperthyroidism is a condition in which
serum levels of T4/T3 are abnormally
high
136
what are the signs of the hyperthriodism
```
Clinical signs: Weight loss, heat
intolerance, increased heart rate,
increased appetite, diarrhea, vomiting,
exophthalmia (associated with Graves’
disease)
```
137
what cause hyperthrodism
• Causes: Auto-antibody stimulation of
TSH receptors (Graves’ disease);
thyroid tumour
138
what is the Goiters
```
Goiters
• Excess growth of
thyroid gland
• Associated with both
hypo- and hyperthyroidism
```
139
see lecture 2 slide 47
140
what kind of the hormon is growth hormon
Protein hormone
141
what is the growth hormone receptor
• Binds to cytokine receptors
142
how long is the growth hormon half life
Half-life: 6-20 mins
143
how does the growth hormon mostly transported
• Mostly transported bound to a binding protein
| GHBP
144
where does growth hormone Synthesized, stored, and secreted?
Synthesized, stored, and secreted by somatotropes
| in the anterior pituitary
145
which tissues are affecetd by the growth hormon and what do they secrecate
growth hormon Signals tissues to produce IGF-1
146
how is the GH secretion patterns
• Pulsatile secretion: GH is secreted as several large
| pulses or peaks each day, 10-30 mins in duration
147
when does the largest gh peak occurs
```
The largest GH peak occurs about 1 hr after onset
of sleep (circadian pattern)
```
148
explain the lifetime of the growth hormone
Lifetime: Overall levels highest early in life; amplitude/frequency are greatest during pubertal growth spurt and then decline throughout adult life
149
what is the result of the studies in the state about the youngsters sleeping and its relationship with the growth hormone
Results from the study in the U.S. showed youngsters bed down for 4.5 hours extra a day for two days just before a growth spurt, taking an average of three extra naps a day.
150
what is the effect of the Sleep Increase, Exercise, Hypoglycemia, Hyperglycemia, High dietary protein,Excess cortisol, Endocrine disruptors, Ghrelin (hunger hormone), IGF-1 & Somatostatin o the growth hormone
```
Sleep Increase
Exercise Increase
Hypoglycemia Increase
Hyperglycemia Decrease
High dietary protein Increase
Excess cortisol Decrease
Endocrine disruptors Decrease
Ghrelin (hunger hormone) Increase
IGF-1 & Somatostatin Decreas
```
151
growth hormone affects the liver to produce which of the compounds
Several classes: IGF-1 through 7 (only discuss IGF-1 and -2)
• Protein/peptide hormone
• Binds to tyrosine kinase receptors
• Half-life: much longer, ~12 hrs
152
where does the IGF-1 many produce and when human have the highest production of it and what it is needed for
Mainly produced in liver Low at birth, high at puberty, lower later
in life Needed for skeletal and extra-skeletal development, adipocyte differentiation
153
where does the IGF-2 is produced
Produced in many developing tissues
Prominent during embryonic/fetal
growth
154
what are the IGF actions
Autocrine
Paracrine
Endocrine
155
what is the relationship between the GH and IGF-1
Take home message: GH stimulates IGF-1 synthesis and release in
many tissues, not just the liver! IGF-1 produced by tissues can act
on the same cell OR another cell within that tissue
156
how does GH exert its effects via IGF-1
GH exerts many of its effects directly on tissues, but also
| indirectly through IGF-1
157
is it easy to differentiate between direct actions of GH and those of
IGF-1
Difficult to differentiate between direct actions of GH and those of
IGF-1
158
do GH and IGF-1 have the same actions
• GH and IGF-1 appear to exert opposite actions in some tissues,
which suggests that they have independent roles
159
what is the other name of the IGF
IGFs are also called
| “somatomedins” – they mediate the effects of GH
160
what is the function of the Liver glucose release on the GH and IGF-1 (SEE LECTURE 3 SLIDE 13 OF THE ENDOCRINOLOGY )
Liver glucose release Increase>GH Decrease> 1GF-1
161
what are the direct act of the GH on the blood and its indirect effect on the musculoskeletal
GH acts directly on many tissues to increase blood levels of fatty acid + glucose
GH acts indirectly through IGF-1 to increase growth of musculoskeletal tissues
162
see lecture 3 slide 15
163
which organ of the body release the GHRH
GHRH is released from hypothalamus
| after a stimulus
164
which organ produces the gh and where does it act on
GH is released from anterior pituitary and acts
| on liver, fat tissue, and other tissues
165
does the igf-1 inhibits the release of the gh which hormone does it promote
IGF-1 produced from liver inhibits release of GH and promotes the production of somatostatin (SST; also called growth hormone inhibiting hormone [GHIH])
166
what is the somatostain
somatostatin (SST; also called growth hormone inhibiting hormone [GHIH])
167
what does IGF-1 increase in the blood and what does it inhibit
increased fatty acids and glucose in the blood will also inhibit GH release
168
see slide 18 of the lecture 3
169
body size increases thanks to what
Body size increases thanks to growth and elongation of the
| skeleton + associated soft tissues (ligaments, tendons, muscles)
170
bones are growth in which dimentions
Bone grows in DIAMETER and in LENGTH during growth phases
171
what is the endochondral ossification process
LENGTH: During endochondral ossification (fetal stage) cartilage
cells “mineralize”, eventually giving way to osteoblasts (bone building
cells)
Some cartilage cells left at the epiphyseal plates continue to
proliferate and mineralize, either becoming bone or allowing nearby
osteoblasts to help build more bone (after birth)
172
how does the bone growth in the diameter
DIAMETER: Osteoblasts lay down more minerals (calcium and
| phosphate) and collagen on the outer surface of the bone
173
what is the result of the GH action on the cartilage cells
GH acts directly on cartilage cells, maintaining a resting population
(resting zone) or helping them mineralize (hypertrophic zone)
174
which organs are affected by the GH for the IGF-1 production
. GH stimulates production of IGF-1
| in liver and in bone
175
how does IGF-1 promote the bone formation
. IGF-1 (local and system) helps stimulate chondrocyte proliferation (proliferative zone), mineralization, and osteoblast activity to promote bone formation
176
see slide 24 of the lecture 3
177
what is the Acromegaly (post-pubertal disorder)
* Hypersecretion of growth hormone after epiphyseal plate closure
* Can result in severe disfigurement
* In >90% of acromegaly patients, the overproduction of GH is caused by a benign pituitary tumour (pituitary adenoma)
178
what is the Gigantism (pre-pubertal disorder)
Hypersecretion of growth hormone before epiphyseal plate closure
• Influences IGF release from the liver and therefore stimulates
extensive bone growth
• Usually caused by a tumour on the anterior pituitary gland
179
what is Dwarfism (pre-pubertal disorder
Dwarfism (pre-pubertal disorder
• Hyposecretion of growth hormone before epiphyseal
plate closure
• Overall reduction in growth; normal body proportions
(limb:torso)
• Differs from achondrodysplasia (short limbs, normal
torso)
180
what is the Dog breeds
Most toy breeds are pituitary (ateliotic) dwarfs (GH deficiency, small all over):
Chihuahuas, Boston Terriers, Italian Greyhounds, Maltese, Miniature Pinschers, Miniature Spaniels, Pomeranians, Toy Poodles, Yorkies, etc.
181
what is the Brachycephalic
Brachycephalic: Boxers (shortened skull bones, short muzzle)
182
what is the Micromelic
Micromelic (short legged) breeds include: Basset Hounds, Bulldogs, Corgis,
Dachshunds, Lhasa Apsos, Scottish Terriers, Shetland Sheepdogs, etc.
183
what is the role of the calcium salt in the body
```
Calcium salts (with phosphate) provide the
structural integrity of bone
```
184
how much calcium are in the body
Total body amount: ~1,200 g of Ca2+ in a
| 70kg human
185
how does the calcium stored in the body
99% of calcium is stored in bones in the
form of hydroxyapatite (Ca10[PO4]6[OH]2)
The rest can be found intracellularly (0.9%)
or extracellularly (0.1%)
186
what is the extracellular ca2+ regulated by
Extracellular Ca2+ is very tightly regulated:
• Ionized Ca2+ (“free”: 50%)
• Protein-bound Ca2+ (40%)
• Ca2+ with PO4 and citrate (10%)
187
Intracellular is associated with :
Intracellular Ca2+ is also tightly regulated:
• Largely associated with membranes in
mitochondria, endoplasmic reticulum and
plasma membrane
188
how we gat most of the calcium of the body and how does it absorbed
Intake: Entirely through diet
~1/3 of calcium is absorbed
through small intestine
Hormone regulated
189
how does the calcium output works
Output: Kidneys
| Our bodies cannot make calcium Lost through urine, so must be replaced through diet
190
what is the Total body calcium
Total body calcium = intracellular + extracellular (ECF/blood + bone)
191
see lecture 3 slide 37
192
what is the Parathyroid hormone (PTH)
```
Parathyroid hormone (PTH)
Peptide hormone produced and secreted by the parathyroid glands
```
193
what are the chief cells in the parathyroid glands produce
Chief cells in parathyroid glands produce
| and secrete PTH
194
what is the relationship between the chief cells and ca2+
Chief cells respond to changes in Ca2+
serum concentration; PTH is secreted
when Ca2+ levels are low
195
can people live without the thyroid
People can live
without a thyroid, but
parathyroid glands are
essential for life!
196
what is the role of the PTH in regulation of Ca2+ levels
1. PTH stimulates osteoclasts to resorb bone (primary mechanism)
2. PTH stimulates kidneys to reabsorb Ca2+ but inhibits reabsorption of PO43-
3. PTH stimulates kidneys to produce the enzyme needed to make 1,25 dihydroxyvitamin D3 to promote better absorption of Ca2+ from food across
the intestinal epithelium
All three mechanisms raise blood Ca2+ levels
197
how does the PTH regulate the CA+2 level
Ca2+-sensitive receptors (CaSR) on
parathyroid cells activate cAMPmediated release of PTH when
Ca2+ signal is missing
PTH then binds to G-proteincoupled receptors on target tissue
(kidney cells, osteoclasts)
PTH is produced/released
continuously, NOT stored
198
is Bone is constantly being formed and
| resorbed (dynamic turnover)
Bone is constantly being formed and
| resorbed (dynamic turnover)
199
what does OsteoCLAST cells do
```
OsteoCLAST cells dissolve
hydroxyapatite (Ca10[PO4]6[OH]2) to
allow free Ca2+ and PO4
3- to move to
the bloodstream
```
200
what do OsteoBLAST cells produce?
OsteoBLAST cells produce and
secrete collagen (part of bone matrix),
which hardens in the presence of
hydroxyapatite
201
how does the CA2+ reabsorption happens
Ca2+ reabsorption primarily takes place in the distal tubules PTH regulates a calcium channel protein to facilitate Ca2+ reabsorption from tubular fluid into
the bloodstream PTH inhibits PO4 3- reabsorption to reduce bone formation
202
how does pth use the vitamin d3 for the regulation
PTH also regulates conversion of a
prehormone (Vitamin D3) to active
hormone 1,25-dihydroxyvitamin D3
203
how does the vitamin d3 synthesized
Vitamin D3 is either synthesized with
exposure to sunlight or ingested through
diet
204
what happens to the vitamin d3 in the liver
Vitamin D3 is converted to 25-
| hydroxyvitamin D3 in the liver
205
what happens for the vitamin d3 in the kidneys
Converted to 1,25-dihydroxyvitamin D3
in kidneys thanks to 1α-hydroxylase
(stimulated by PTH)
206
what are the primary and secondary mechanism of the d3
```
Primary mechanism: Stimulates active
transport of Ca2+ from intestine to
bloodstream when [Ca2+] is low
Secondary mechanism: Active
reabsorption of Ca2+ AND PO43- from kidney
```
207
does d3 provide ca2+ and po4-3
Provides Ca2+ and PO43- for bone deposition
208
what happens when there is a ca2+ deficiency
When diet is Ca2+ deficient: Stimulates
the production of more osteoclasts
(primary goal ALWAYS is to raise blood Ca2+)
209
how do the PTH and 1,25-dihydroxyvitamin D3 increase blood Ca2+
Together, PTH and 1,25-dihydroxyvitamin D3 increase blood Ca2+ by:
1. Increasing intestinal absorption of Ca2+
2. Promoting osteoclast activity
3. Increasing Ca2+ reabsorption in kidney Increased Ca2+ levels leads to reduces PTH secretion
210
what is the Calcitonin produced by
Calcitonin is released by parafollicular
cells of the thyroid (C cells) when Ca2+
levels are high
211
what is the role of the calcitonin in the adult humans
Plays only a minor role in adult humans
Peptide hormone that is stored until
needed (hypercalcemic conditions)
212
what is the emergency role of the calcitanin
May work as an “emergency” hormone
| to maintain homeostasis
213
what is the opposing effect of the calcitonin against pth
Opposes PTH effect in kidneys and bone
| to lower blood Ca2+
214
what is the Hyperparathyroidism
Hyperparathyroidism
Non-cancerous growth on the parathyroid
gland(s) causes hypersecretion of PTH
215
what are the Clinical signs and characteristics of Hyperparathyroidism
```
Clinical signs and characteristics:
• Hypercalcemia
• Increased bone reabsorption
(increased risk of fractures;
osteoporosis)
• Appetite loss/weight loss
• Mineralization of soft tissues
```
216
what causes the Secondary hyperparathyroidism
Secondary hyperparathyroidism
can arise due to kidney failure or
vitamin D deficiency
217
what is the Hypoparathyroidism
Causes: Idiopathic (ie. Unknown cause);
immune-mediated, or iatrogenic
(“physician-associated”; thyroid removal
218
what are the clinical signs of the Hypoparathyroidism
```
Clinical signs and characteristics:
• Hypocalcemia + hyperphosphatemia
• Muscular weakness
• Cardiac arrhythmias
• Seizures
```
219
what is the Rickets
```
Malnutrition resulting in severe
calcium and vitamin D deficiency in
young individuals
Bone malformations, enlarged
weakened joints, soft skull
```
220
what is the Osteomalacia
Osteomalacia
Vitamin D deficiency and low dietary calcium
in older individuals
Bone “softening” leading to increased fracture
risk, spinal deformation, bone changes
221
what is the Osteoporosis
Most common bone disorder
• Bone matrix becomes thinner (less collagen +
hydroxyapatite) due to an imbalance between
bone formation and bone resorption
• Higher risk of bone fractures
222
what are the risk factors for the Osteoporosis
Known RISK factors include:
• Age (risk doubles every 5 years between 40 and 60)
• Sex (females are more at risk after menopause)
• Calcium deficient diet or malabsorption
disorders
• Previous fractures
223
how to prevent the osteoporosis
• Prevalence: Fractures from osteoporosis are more common than heart attack, stroke and breast cancer combined. More than 2 million Canadians have osteoporosis, 80% of which identify as women
224
how much is the coast of the osteoporosis
• Costs: $1.9 billion/year, Canada alone
225
how to prevent the osteoporosis
Osteoporosis
Treatment
• Diet modification: Adequate calcium and Vitamin D intake; bone mass begins to decline after 30 years old
• Hormone therapy: Exogenous PTH analogues (low, infrequent doses) and calcitonin can help limit improve bone mineral density (limiting osteoclast activity and/or promoting bone formation); estrogen replacement therapy can be helpful in menopausal women
• Estrogen plays a role in bone formation, and thus menopause presents an osteoporosis risk because of the decline in estrogen
226
how to prevent the Osteoporosis
BEST TREATMENT IS PREVENTION!
• Calcium-rich foods, vitamin D supplementation
• Physical exercise (emphasis on resistance exercises
227
what is the GnRH
Peptide hormone, G-protein coupled receptor
228
how is the GnRH secretion
• Pulsatile secretion (not continuous secretion) results in release of LH/FSH from anterior pituitary (consistent pulses in males; differs in females)
229
what is the FSH hormone
Peptide hormone, G-protein coupled receptor
• Acts on Sertoli cells within seminiferous tubules
to support spermatogenesis
• Sertoli cells also produce inhibin, a peptide hormone,
to inhibit FSH release from AP
230
what is the LH (Luteinizing Hormone)
• Peptide hormone, G-protein coupled receptor
• Acts on Leydig cells (located between the tubules)
to stimulate them to secrete testosterone
• Testosterone subsequently inhibits release of LH and GnRH
231
how does the gonadal axis affect the Embryonic stage of male
Gonadal axis ACTIVE, FSH/LH
promotes differentiation of
gonads/gametes into
testes/spermatogonia
232
how does the gonadal axis affect the Pre-puberty stage of male
Gonadal axis SUPPRESSED
233
how does the gonadal axis affect Puberty & onwards of male
Gonadal axis ACTIVE, FSH/LH promotes volume increase and final sperm maturation
234
what kind of hormones is testosterone and what kind of the receptors does it have
Steroid hormone, intracellular receptor
235
what is the • Major androgen produced in the body
testostron
236
what is the testosterone produced by
• Produced by Leydig cells upon stimulation by LH
237
what is the testosterone converted from
```
Converted from pregnenolone in mitochondria of
Leydig cells (see Steroid Production in Endo Lecture 2)
```
238
what are the role of the testosterone in the body
Sex determination> Development of male primary sex characteristics
(gonads and accessory organs; see future Repro
lectures)
Spermatogenesis.At puberty: Complete maturation of sperm
After puberty: Maintenance of spermatogenesis
Secondary sex characteristics> Growth and maintenance of primary and
accessory sex organsGrowth of facial and axillary hair Body growth
Anabolic effects> Protein synthesis + muscle growthGrowth of bones Growth of other organs (like larynx)
239
what are the Anabolic-androgenic steroids
• Synthetic derivatives of testosterone
240
did canada approved the hypogonadism
FDA/Health Canada approved treatment for
hypogonadism, delayed puberty in boys, or other
gonadal axis dysfunction
241
what is the Unapproved use of Anabolic-androgenic steroids
Unapproved use: Performance enhancement (gain
| of muscle mass/strength for sports-related activities)
242
are the derivatives of the Anabolic-androgenic steroids more anabolic or androgenic
• Derivatives are more anabolic than androgenic
243
what are the side effects of the Anabolic Steroids
Hormonal effects (in males):
• Decreased sperm production
• Decreased size of testes
• Increase in breast tissue size
244
why anabolic steroids have the side affect
Testosterone derivatives shut down gonadal axis
• ↓ FSH/LH = suppressed sperm development, ↓
production of endogenous testosterone
245
what is the gynecomastia
Testosterone/estrogen imbalance in breast
| tissue causes gynecomastia
246
what is the conterception
```
Contraception (or birth control) is any method
used to prevent pregnancy
Can be hormonal-based or non-hormonal
(barrier)-based (condoms, diaphragms,
vasectomy) to prevent fertilization
```
247
what is the Goal of hormonal-based contraceptives:
Goal of hormonal-based contraceptives:
Pharmacological agents that prevent ovulation
(females) OR prevent spermatogenesis (males)
248
what is the synthetic progesterone in the body
Progestin (synthetic
progesterone, an
ovarian steroid) also
inhibits the gonadal axi
249
what is the progestron
Progesterone: Produced from
pregnenolone in theca cells and
granulosa cells of ovaries
250
what is the estradiol
Estradiol (type of estrogen):
Produced from androgens
(androstenedione/testosterone) in
granulosa cells of ovaries
251
what is the difference between men and female in terms of the estrogen and progesterone hormones
Females with ovaries have higher
| estrogen:testosterone than males
252
does fsh/lh act on the ovaries
FSH/LH act on ovaries
253
does ovaries make estradiol
Ovaries make estradiol that influences egg (ovum)
| release into the fallopian tube
254
what are the progesterone and estradiol produce by
Estradiol and progesterone produced by ovaries act on
| the uterus
255
what is the role of the uteres
Uterus prepares for pregnancy; lining is shed if
| implantation does not occur
256
what does UTERINE/MENSTRUAL CYCLE: do
UTERINE/MENSTRUAL CYCLE:
| Prepare uterus for implantation of fertilized ovum
257
what does the OVARIAN CYCLE do
```
OVARIAN CYCLE:
Prepare egg (ovum) for ovulation
```
258
what is the The Ovarian Cycle
Low frequency GnRH pulses stimulate FSH production and release from anterior pituitary
• Follicles containing immature ova respond to FSH and grow (follicular phase)
• Granulosa cells within follicles produce and secrete estradiol (a form of estrogen)
• Estradiol acts on hypothalamus to increase frequency GnRH pulses (POSITIVE FEEDBACK)
Increased frequency of GnRH pulses thanks to estradiol = more LH secretion (LH surge)
• LH surge triggers ovulation; remaining follicle becomes corpus luteum
• Corpus luteum produces and secretes progesterone (along with estradiol); luteal phase
• Combined, estradiol and progesterone inhibit LH/FSH secretion through NEGATIVE FEEDBACK
