Endo pre-clinical (lectures) Flashcards
(193 cards)
1
Q
What are the two main types of hormones?
A
Steroid hormones and non-steroid (peptide/protein) hormones
2
Q
What are steroid hormones made of and where are they produced?
A
- Made from cholesterol
- produced in adrenal glands and gonads (testes/ovaries)
3
Q
How do steroid hormones travel and act on target cells?
A
- They are hydrophobic, so travel through the bloodstream bound to transport proteins
- When they reach their target cell, they are able to diffuse across the cell membrane/phospholipid bilayer (as they are small and non-polar)
- Once inside the cell, they bind to intracellular receptors to affect gene expression in the nucleus
4
Q
What are peptide hormones made of and give example of a peptide hormone
A
- Chains of amino acids
- eg. insulin, glucagon
5
Q
How do peptide hormones act on target cells?
A
- They are hydrophilic -> meaning they can travel easily in the bloodstream
- Once they reach their target cell, they cannot get through the phospholipid bilayer
- They therefore have to bind to a surface receptor protein -> this causes it to change shape -> triggering intracellular signalling pathways that affect gene expression within the cell
6
Q
Why can’t peptide hormones enter cells directly?
A
They are hydrophilic and cannot cross the phospholipid bilayer
7
Q
From what are amino acid hormones derived?
A
Tyrosine
8
Q
Which hormones are amino acid-derived?
A
Thyroid hormones, adrenaline, and noradrenaline
9
Q
Which amino acid hormones act like steroid hormones?
A
Thyroid hormones -> bind to transport proteins to travel in the bloodstream, can diffuse across cell membrane and bind to intracellular receptors to affect gene expression
10
Q
Which amino acid hormones act like non-steroid (peptide) hormones?
A
Adrenaline and noradrenaline -> travel through blood unbound and bind to surface recptor proteins on their target cell to induce intracellular changes
11
Q
What are the two lobes of the pituitary and their tissue type?
A
- Anterior -> glandular
- Posterior -> neural tissue
12
Q
How does the hypothalamus regulate the anterior pituitary?
A
hypothalamo-hypophyseal portal system -> using releasing/inhibiting hormones
13
Q
Name the 4 stimulatory (releasing) hypothalamic hormones
A
- Thyrotropin-releasing hormone (TRH)
- Corticotropin-releasing hormone (CRH)
- Gonadotropin-releasing hormone (GnRH)
- Growth hormone-releasing hormone (GHRH)
→ these stimulatory hormones stimulate the anterior pituitary to produce its own hormones
14
Q
What does TRH stimulate?
A
Stimulates ant. pituitary to produce TSH -> acts on thryoid gland -> increases production of thyroid hormones (T3/T4)
- then when plasma levels of thyroid hormone increase → sends negative feedback signal to the anterior pituitary to make less TSH
15
Q
What does CRH stimulate?
A
Stimulates ant. pituitary to produce ACTH -> acts on adrenal glands (adrenal cortex) -> increases production of cortisol
- then when plasma levels of cortisol increase → sends negative feedback signal to the anterior pituitary to make less ACTH
16
Q
What does GnRH stimulate & what is the exception in terms of negative feedback?
A
Stimulates ant. pituitary to produce gonadotropins (FSH & LH) -> act on the gonads -> regulates production and maturation of gametes + production of sex hormones
- gametes: testes (sperm), ovaries (oocytes)
- sex hormones: testosterone, oestrogen, progesterone
.
- sex hormones send a negative feedback signal to the pituitary to make less gonadotropins (FSH & LH)
.
Exception is in females -> right before ovulation oestrogen levels are really high → this makes the pituitary even more sensitive to GnRH
→ this is a positive feedback signal → causes a massive release/surge of FSH and LH to cause ovulation
17
Q
What does GHRH stimulate?
A
Stimulates ant. pituitary to produce growth hormone (GH) –> has a direct effect on long bones & other tissues in body (stimulating growth)
18
Q
What are the 2 inhibitory hypothalamic hormones?
A
- Growth hormone inhibiting hormone (GHIH) → also called Somatostatin
- Prolactin inhibiting factor → also called Dopamine
19
Q
What inhibits prolactin secretion & how is prolactin regulated during breastfeeding and the rest of the time when not breastfeeding?
A
Prolactin inhibiting factor (dopamine) → works slightly differently as needs to be continuously produced outside of breastfeeding (ie. to tell the anterior pituitary to inhibit prolactin production)
- prolactin increases milk production in the breasts
→ during breastfeeding, the baby suckling sends a signal to hypothalamus to stop prolactin inhibiting factor (dopamine) → allowing prolactin to be produced by the anterior pituitary and breastfeeding can occur
20
Q
Which hormones are secreted by the posterior pituitary?
A
The nuclei of the hypothalamus (paraventricular & supraoptic nuclei) secrete:
- Antidiuretic hormone (ADH)/Vasopressin
- Oxytocin
21
Q
How is the hypothalamus connected to the posterior pituitary and where are hormones stored (ready to be released)?
A
- by the pituitary stalk –> this stalk is made up of hypothalamic neurons coming from the paraventricular and supraoptic nuclei
→ these hormones travel down the stalk, and are stored in areas within the stalk walls called Herring bodies, which store the hormones until they get a signal to release them
22
Q
What stimulates ADH release and its function?
A
High blood osmolarity OR a low blood volume
–> ADH retains water from the urine + causes vasoconstriction of blood vessels (decreases osmolarity & increases BP)
23
Q
What stimulates oxytocin release and its function?
A
Signal is generally low apart from motherhood (and can also increase a bit during pleasant social interactions - eg. hug, physical contact, orgasm)
–> Oxytocin dilates cervix + stimulates uterine contractions during childbirth + contracts muscle cells in breasts (to eject the milk during breastfeeding)
24
Q
What does the pineal gland produce?
A
- The pineal gland is made up of pinealocytes → synthesise and release melatonin
- Melatonin is mostly secreted during the night → regulates our body’s circadian rhythm
(ie. inner clock that tells us when we should be sleeping and when we should be awake)
25
What do thyroid follicular cells produce + function?
- produce triiodothyronine (T3) + thyroxine (T4)
- Once inside the cell → T4 is mostly converted into T3 (active form)
→ T3 speeds up the basal metabolic rate
26
What do parafollicular cells (C-cells) produce & what does PTH do?
- Parafollicular cells -> produce Calcitonin → lowers blood calcium
- PTH increases blood calcium -> acts on bone, kidneys, and gut
(calcitonin & PTH work together to maintain calcium homeostasis)
27
The adrenal cortex (outer layer of adrenal gland) can be further divided into 3 zones, what are they & what is produced by each?
- Zona glomerulosa → aldosterone
- Zona fasciculata → cortisol
- Zona reticularis → makes small amounts of sex hormone precursors
28
What triggers aldosterone and its function?
Low BP or high K⁺ → retains Na⁺ and water, excretes K⁺
(ie. increases sodium and water reabsorption + potassium excretion)
29
What cells produce insulin and glucagon?
- Beta cells → insulin
- Alpha cells → glucagon
30
What are the endocrine and exocrine roles of the pancreas?
- Endocrine → produces insulin and glucagon
- Exocrine → secretes digestive enzymes into duodenum
31
What type of innervation do endocrine glands receive?
Autonomic nervous system innervation
32
What is the blood supply to the hypothalamus?
Branches of the Circle of Willis
33
Where is the pituitary gland located?
In the sella turcica (a saddle-shaped recess of the sphenoid bone)
34
What supplies blood to the pituitary gland?
Internal carotid artery and branches from the brain via the pituitary stalk
35
What is the function of the anterior pituitary?
Produces hormones that stimulate the thyroid, adrenal glands, gonads, as well as GH and lactogenic factors
36
What hormone is produced by the pars intermedia (middle pituitary)?
Melanocyte-stimulating hormone (MSH)
- influences skin pigmentation (MSH stimulates melanin production in melanocytes, leading to darker skin pigmentation)
37
What is the function of the posterior pituitary?
Releases hormones that raise BP, decrease urine output, and contract the uterus
- ie. ADH and oxytocin
38
What visual field defect can occur due to enlargement of the pituitary?
Bitemporal hemianopia due to compression of the optic chiasm
39
Where is the pineal gland located?
a pea-sized gland that lies deep in the brain just above the thalamus where the two halves of the brain join behind the third ventricle
40
What is the blood supply to the pineal gland?
Branches of the posterior cerebral artery.
41
Where is the thyroid gland located?
Anterior to the larynx and trachea, with two lobes connected by an isthmus (typically between 2nd and 4th tracheal rings)
42
What is the blood supply to the thyroid gland?
Superior thyroid artery (1st branch of external carotid) and inferior thyroid artery (thyrocervical branch of the subclavian artery)
43
What is the function of the thyroid gland?
Produces T3 and T4 hormones that regulate metabolism
- T4 (inactive form) makes up 95% of thyroid hormone found in circulating blood
- T4 is converted to T3 (active form) by the removal of an iodine atom --> this occurs mainly in the liver and in certain tissues where T3 acts, such as in the brain
44
Which nerve is closely related to the thyroid gland and at risk in surgery?
Recurrent laryngeal nerve
45
What is a clinical sign of thyroid enlargement?
Goitre, which may compress the trachea if very large
46
Where are the parathyroid glands located?
Usually four glands behind the lateral lobes of the thyroid
47
What is the blood supply to the parathyroid glands?
Chiefly from the inferior thyroid artery (as this artery supplies the posterior aspect of the thyroid gland - where the parathyroids are located)
48
What is the function of the parathyroid glands?
Regulate calcium levels via secretion of parathyroid hormone (PTH)
49
What is a surgical risk involving the parathyroid glands?
Accidental removal during total thyroidectomy → hypocalcemia
(due to close relationship to the thyroid gland)
50
Where are the adrenal glands located?
On the superior poles of the kidneys, retroperitoneal, either side of the aorta and IVC
51
What are the arteries supplying the adrenal glands?
Superior, middle, and inferior adrenal arteries
52
What is the function of the adrenal glands?
Secrete hormones for metabolism, BP, immune function, and stress response
53
Why are adrenal masses not palpable?
As they are located retroperitoneally and therefore suspected masses need to be investigational by cross-sectional imaging
54
Where is the pancreas located?
Retroperitoneal; head lies in the duodenum's C-shape, body over the aorta/IVC, tail extends to spleen
55
What is the pancreas’s blood supply?
Superior pancreaticoduodenal & splenic arteries (coeliac axis), and inferior pancreaticoduodenal (SMA)
56
What are the pancreas's two main functions?
- Endocrine: regulates blood sugar by secreting gormones (insulin & glucagon) from islets of Langerhans into the blood
- Exocrine: secretes digestive enzymes (proteases, lipases, amylase) into the duodenum
57
Where is pain from pancreatitis typically felt?
In the back (due to retroperitoneal location)
58
Where are the ovaries located?
In the pelvis, either side of the uterus
59
What arteries supply the ovaries?
Ovarian and uterine arteries
60
What are the two main functions of the ovaries?
- Hormonal function -> producing oestrogen and progesterone
- reproductive function -> producing eggs (oocytes)
61
How can ovarian cancer spread?
Via paraaortic lymph nodes (lymph follows blood supply) and transperitoneally (throughout intraperitoneal cavity)
62
Where are the testes located?
In the scrotum
63
What is the arterial supply and venous drainage of the testes?
- Arterial --> testicular arteries (from abdominal aorta)
- Venous --> right → IVC, left → left renal vein
64
What are the functions of the testes?
- Hormonal function --> produces testosterone
- Reproductive function --> produces sperm
65
How can testicular cancer spread?
To paraaortic lymph nodes (follows arterial supply path)
66
What are the four anatomical parts of the pancreas & answer the following:
- where is the head of the pancreas located?
- what anatomical structure does the neck of the pancreas sit on?
- Which part of the pancreas invaginates into the hilum of the spleen?
- Head --> in the ‘C-loop’ of the duodenum (D1 and D2)
- Neck --> sits on the portal vein
- Body
- Tail --> the tail
67
What is the uncinate process derived from embryologically?
The ventral pancreas
68
What embryological structure forms the majority of the pancreas (except the uncinate process)?
The dorsal pancreatic bud
69
What artery runs along the top of the pancreas?
The splenic artery
70
What nerves supply the pancreas?
Parasympathetic --> vagus nerve
- Sympathetic --> coeliac ganglia (splanchnic nerves)
71
What is the anatomical position of the pancreas in relation to the stomach and peritoneum?
Retroperitoneal, lies posterior to the stomach and anterior to the lesser sac
72
How can a biopsy of the tail of the pancreas be performed?
Via the posterior wall of the stomach using the lesser sac
(as stomach lies anterior to the pancreas)
73
What two major arteries supply the pancreas?
The celiac trunk and the superior mesenteric artery (SMA)
- Head of pancreas --> superior pancreaticoduodenal artery (from celiac trunk), Inferior pancreaticoduodenal artery (from SMA)
- Body and tail of pancreas --> Pancreatic branches of the splenic artery
(The superior and inferior pancreaticoduodenal arteries form an ansatomotic arcade around the head of the pancreas)
74
What veins drain the pancreas?
The splenic vein and the superior mesenteric vein, which combine to form the portal vein
75
Why is dual blood supply to the pancreas clinically significant?
Maintains perfusion during surgery or trauma (e.g. Whipple's procedure)
76
Name the hormones secreted by different pancreatic endocrine cells.
- **α - cells (alpha cells)**
- **β - cells (beta cells)**
- δ - cells (delta cells)
- PP cells
- ε - cells (epsilon cells)
- **α - cells → glucagon**
- **β - cells → insulin**
- δ - cells → somatostatin
- PP cells → pancreatic polypeptide
- ε - cells → ghrelin
77
What are the three forms of nutrients absorbed after eating?
Amino acids, fats, and carbohydrates (glucose)
(carbs are main source of energy)
78
Insulin is released after you eat a meal to regulate blood glucose levels (to avoid hyperglycaemia). Name the 3 main metabolic actions of insulin.
- Glycolysis: glucose → ATP (energy to be used anywhere in body)
(irreversible process)
- Glycogenesis: glucose → glycogen (short-term storage)
--> glycogen = a heavily branched polymer with lots of glucose molecules stacked on it
(reversible process)
- Lipogenesis: glucose → lipids (long-term storage)
--> stored in adipose tissue (irreversible)
79
What effect does insulin have on glucagon?
It inhibits glucagon release
80
Glucagon is released when blood glucose levels drop too low (hypoglycaemia). Name the 3 main actions of glucagon.
- Glycogenolysis: glycogen → glucose
(reversible process)
- Gluconeogenesis: amino acids → glucose
(reversible process)
- Ketogenesis: fatty acids → ketone bodies (the body does this when in starvation mode → ketone bodies are forms of energy to be used only by the heart and brain (not the rest of the body)
81
In order for insulin to be released, glucose needs to enter the pancreatic beta-cells. Explain the process of how glucose enters the cell, moves through the cell, and ultimately triggers insulin to be released.
1. Glucose enters pancreatic beta cells via GLUT-2 transporters (faciliated diffusion)
- Inside the cell, glucose is phosphorylated by glucokinase to form glucose-6-phosphate
- This is metabolised through glycolysis to form pyruvate, which enters the Krebs cycle in mitochondria
- The Krebs cycle generates ATP from ADP, increasing the ATP:ADP ratio
2. ATP-sensitive potassium (K+) channels:
- These channels are regulated by intracellular energy levels --> **ADP** keeps them **open** & **ATP** keeps them **closed**
- Resting membrane potential: inside of the cell is **negative** (~**–70 mV**), outside is positive.
- As ATP levels **rise** and ADP **falls**, **K⁺ channels close**, preventing potassium from leaving the cell (ie. ATP keeps channels closed)
- Accumulation of K⁺ inside the cell causes **depolarisation**.
- If membrane potential reaches around **–50 mV**, **voltage-gated calcium channels open**
3. Calcium-mediated insulin release:
- **Extracellular Ca²⁺** rushes into the cell.
- **Intracellular vesicles** containing insulin are triggered by calcium to **fuse with the membrane**, releasing **insulin via exocytosis**.
82
How do amino acids and fatty acids promote insulin secretion?
- Feed into the **Krebs cycle**, increasing ATP production.
- **Positively charged amino acids** (e.g., **arginine**) also **depolarise** the membrane directly.
(Some amino acids enter the cell **with Na⁺**, further contributing to depolarisation)
83
How does parasympathetic stimulation affect insulin secretion?
Vagus nerve releases acetylcholine → enhances insulin release
84
How does sympathetic stimulation affect insulin secretion?
Preganglionic neurons from thoracolumbar spinal cord stimulate adrenal medulla → release adrenaline and cortisol
- Cortisol - increases blood glucose via glycogenolysis (tells glycogen to be broken down to release glucose) --> indirectly stimulating insulin release.
- Adrenaline - promoted glycogenolysis
--> low levels: binds β₂-adrenoceptors → enhances insulin release
--> high levels: activates α₂-adrenoceptors → inhibits insulin release
85
What are incretins, and how do they affect insulin?
- GLP-1 (glucagon-like peptide 1) --> secreted from small intestine
- GIP (gastric inhibitory peptide) --> secreted from stomach and duodenum
--> Enhance glucose-dependent insulin secretion
.
(note: GLP-1 is named that because has same precursor (preglucagon) as glucagon, but they have distinct actions)
86
Which other gut hormones (apart from GIP and GLP-1) modulate insulin?
- Cholecystokinin (CCK) --> also promotes insulin release.
- Somatostatin --> acts as a negative regulator, inhibiting insulin release.
87
What is MODY and what causes it?
Maturity Onset Diabetes of the Young; caused by glucokinase mutations
- Leads to poor glucose sensing → inadequate insulin release → hyperglycaemia
88
How does T2DM affect insulin secretion?
- can result from chronic overstimulation of insulin secretion (e.g., prolonged stress, obesity).
- **Beta-cell exhaustion** leads to impaired insulin secretion
89
How do sulfonylureas stimulate insulin release?
- **Block ATP-sensitive K⁺ channels**, mimicking high ATP levels.
- K⁺ stays inside cell → **depolarisation** → **Ca²⁺ influx** → **insulin release**
90
Explain this diagram.
- The insulin response is less pronounced than with oral glucose because of the incretin effect
- oral glucose triggers the release of incretin hormones (GLP-1 and GIP) from the gut - which stimulate insulin secretion in response to glucose
- This effect is absent when glucose is given intravenously
91
What is the relationship between the hypothalamus and the pituitary gland?
The hypothalamus is a neuroendocrine structure above the brainstem
- it connects to the pituitary gland (below) via the infundibulum (pituitary stalk)
92
What are the two parts of the pituitary gland and their tissue types?
- Anterior pituitary (adenohypophysis) --> endocrine tissue.
- Posterior pituitary (neurohypophysis) --> neural tissue, considered an extension of the hypothalamus
93
How does the hypothalamus communicate with the anterior pituitary?
Via the hypophyseal portal system.
94
Is the posterior pituitary a true endocrine gland?
No; it stores and releases hormones produced in the hypothalamus
95
What hormones are released by the posterior pituitary and where are they made?
- Oxytocin (paraventricular nucleus)
- ADH/vasopressin (supraoptic nucleus)
96
Which hypothalamic hormones regulate the anterior pituitary, and what do they stimulate?
- TRH → TSH
- CRH → ACTH
- GnRH → LH & FSH (gonadotropins)
- GHRH → GH
- PRH → Prolactin
→ The anterior pituitary then releases its hormones into the bloodstream, producing widespread systemic effects.
97
What is the central role of the HPA axis?
To regulate the stress response through cortisol release.
98
Describe the physiological cascade of cortisol release.
1. **Stressful stimulus →** activates the **cerebral cortex**.
2. This stimulates the **hypothalamus** to release a neuropeptide called **CRH (corticotropin-releasing hormone)**.
3. **CRH** travels via the **hypophyseal portal system** to the **anterior pituitary** (blood vessels that connect the hypothalamus to the anterior pituitary)
4. The **anterior pituitary** releases **ACTH (adrenocorticotropic hormone)** into the bloodstream.
5. **Systemic ACTH** acts on the **adrenal cortex** (zona fasciculata) to release cortisol into the bloodstream
99
Where is cortisol produced and what type of hormone is it?
In the zona fasciculata of the adrenal cortex; it is a glucocorticoid steroid hormone.
100
What are the actions of cortisol on extrahepatic tissues (eg. muscle)?
- ↓ Glucose uptake → preserves glucose for essential organs (ie. brain)
- ↓ Amino acid uptake
- ↓ Protein synthesis (to conserve ATP).
- ↑ Protein breakdown → increases circulating amino acids for gluconeogenesis or as alternative fuel + amino acids used for gluconeogenesis
.
--> main goal is to provide glucose for essential organs
101
What are the actions of cortisol on adipose tissue?
- ↓ Fat uptake.
- ↑ Lipolysis → releases free fatty acids for energy
(Note: Fatty acids are used by non-brain tissues for energy → glucose-sparing effect.)
102
What are the actions of cortisol on the liver?
- ↑ Gluconeogenesis (main goal: increase plasma glucose).
- ↑ Glycogen storage (prepares for ongoing stress).
103
What is the overall goal of cortisol during stress?
To mobilise energy stores during stress by increasing glucose availability (especially for the brain), while encouraging other tissues to rely on fatty acids and amino acids
104
How is cortisol secretion regulated?
High cortisol inhibits CRH (hypothalamus) and ACTH (anterior pituitary) to turn off the HPA axis
- this switches off the stress response once resolved
105
What are the key cell types in the thyroid and their functions? (3)
- **Follicular cells**: store and produce thyroid hormone (activity depends on TSH)
- **Colloid**: contains thyroglobulin (storage form of thyroid hormones)
- **Parafollicular cells (between follicles)**: produce calcitonin
.
(Note: Vascularity changes with activity of gland --> ie. more blood supply with increased activity)
106
Which hormones are released by the thyroid and from what amino acid are they derived?
- T3 and T4 --> both derived from tyrosine
- T4 - 90% of output (and what is measured on bloods)
- T3 - biologically active (T4 converted to T3 intracellularly)
107
Thyroxine and T3 have iodines on both inner and outer benzene rings - crucial for biological activity (this is why we need iodine/iodide in diet to make thyroid hormone).
What is the role of deiodinases?
Convert T4 to T3 by removing iodines; three types exist with tissue-specific expression
- Type 1: present in thyroid, liver, kidney (sensitive to propylthiouracil)
- Type 2: widespread (ie. expressed everywhere)
- Type 3: expressed only in brain & placenta
108
Iodine is required for thyroid hormone synthesis. What are some sources of iodine?
fish, seaweed, dairy, iodised salt
109
Outline the steps in thyroid hormone synthesis.
1. **Iodide uptake →** via Na+/I- symporter (NIS) on basolateral membrane.
2. **Thyroglobulin synthesis & secretion →** thyroglobulin is secreted into colloid space (**exocytosis)**
3. **Iodide secretion** into colloid via Pendrin
4. **Iodination**: iodide → iodine (peroxidation using hydrogen peroxide) → reacts with thyroglobulin tyrosines.
5. **Organification & coupling** via thyroid peroxidase (TPO) to form T3/T4.
- “**Organification**” → refers to the process of incorporating iodine into tyrosine residues on the thyroglobulin protein, a crucial step in hormone production
- “**Coupling**" → refers to the subsequent step where these iodinated tyrosine residues (MIT and DIT) are linked together to form the active thyroid hormones T3 and T4
6. **Colloid reuptake & degradation**: lysosomes (cathepsins) release T3/T4 into blood
110
What enzyme is essential for iodination and coupling of thyroglobulin to be able to synthesise T3 and T4 hormones?
Thyroid peroxidase (TPO).
111
What dietary element is crucial for thyroid hormone production?
Iodine
112
Where is TSH produced and how is it regulated?
Made by anterior pituitary thyrotrophs
- controlled by hypothalamic TRH via hypophyseal portal system
113
What pathway is activated when TSH binds to TSH receptors on basal membrane of follicular cells?
activates Gs protein → cAMP → PKA → T3/T4 synthesis.
114
Other than on the surface of thyroid follicular cells, where else are TSH receptors found (clinically relevant)?
TSH receptors are also found on extraocular muscles → explains Graves' eye findings.
115
What is Graves’ disease and its key features?
Autoantibodies stimulate TSH receptors --> hyperthyroidism (primary)
- exophthalmos, pretibial myxoedema
116
What is Hashimoto’s thyroiditis?
Autoimmune destruction of the thyroid; TSH receptor antibodies block signalling → hypothyroidism
117
Explain the uptake on a radioactive iodine (1, 2, 3 iodine) scan for the following conditions:
- Graves’
- toxic adenoma
- multinodular goitre
- Graves’ = diffuse uptake
- toxic adenoma = focal uptake
- multinodular goitre = patchy uptake
118
What is the Wolff-Chaikoff effect?
Large iodine doses inhibit thyroid hormone synthesis
119
What happens to T4 inside the cell?
It is mostly converted into T3 by intracellular deiodinases
120
What is the effect of thyroid hormones on metabolic rate?
They increase the basal metabolic rate
121
How do thyroid hormones affect glucose and fat metabolism?
They increase gluconeogenesis, protein breakdown, and lipolysis
122
What is the role of thyroid hormones in thermogenesis?
They increase uncoupling proteins (UCP) in brown fat to generate heat
123
How do thyroid hormones influence the autonomic nervous system?
↑ β-adrenergic receptor expression → ↑ sympathetic activity
124
Describe the process of TRH being released from hypothalamus to T3 and T4 (thyroid hormones) being released.
- Hypothalamus produces TRH → TRH goes down hypophyseal portal system to anterior pituitary
- TRH binds to TRH receptor on thyrotrophs → causing release of TSH from anterior pituitary gland
- TSH then circulates in blood until it reaches thyroid gland (target organ) → binds to TSH receptors on follicular cells → stimulates thyroid hormones (T3 and T4) to be released
125
How do T3 and T4 regulate the HPT axis via negative feedback?
- Direct feedback: T4/T3 can go into cells of the pituitary (thyrotrophs) and hypothalamus → turn off TSH/TRH secretion
- Indirect feedback: T4/T3 reduce expression of TRH receptor on pituitary thyrotrophs → to make them less responsive to TRH
126
Which hormones inhibit TSH secretion?
Somatostatin and dopamine.
127
What is the role of leptin in thyroid hormone regulation?
High leptin (from increased fat mass) increases TRH/TSH → boosts thyroid hormone production → increases metabolism
128
What does the following thyroid bloods indicate:
- Low T4, Low T3, Raisd TSH
primary hypothyroidism
129
What does the following thyroid bloods indicate:
- High T4, High T3, Low TSH
primary hyperthyroidism
130
What does the following thyroid bloods indicate:
- Low T4, Low T3, Low TSH
secondary/tertiary hypothyroidism (problem in pituitary/hypothalamus)
131
What does the following thyroid bloods indicate:
- High T4, High T3, High TSH
secondary/tertiary hyperthyroidism (pituiary/hypothalamus)
132
What does the following thyroid bloods indicate:
- Low/normal T4, Low T3, Normal TSH
sick euthyroid syndrome
- normal T4, but problem converting T4 to T3 (during acute or chronic illness)
133
1) In response to a physiological stimulus such as the stress of taking an important test, which of the following reflects the most likely sequence of events?
- increased cortisol, increased corticotropin, increased corticotropin-releasing hormone
- Increased corticotropin-releasing hormone, increased corticotropin, increased cortisol
- Increased cortisol, decreased corticotropin, increased corticotropin-releasing hormone
- Increased corticotropin-releasing hormone, increased corticotropin, decreased cortisol
- Increased cortisol, increased corticotropin, decreased corticotropin-releasing hormone
Increased corticotropin-releasing hormone, increased corticotropin, increased cortisol
134
2) Cortisol is a(n)...
- Mineralocorticoid
- Glucocorticoid
- Androgen
Glucocorticoid
135
3) Which of the following best describes the metabolic actions of cortisol?
- Increases muscle glucose uptake, increases muscle amino acid uptake, increases adipose tissue fat uptake
- Increases muscle glucose uptake, decreases muscle amino acid uptake, increases adipose tissue fat uptake
- Decreases muscle glucose uptake, decreases muscle amino acid uptake, increases adipose tissue fat uptake
- Decreases muscle glucose uptake, increases muscle amino acid uptake, decreases adipose tissue fat uptake
- Decreases muscle glucose uptake, decreases muscle amino acid uptake, decreases adipose tissue fat uptake
Decreases muscle glucose uptake, decreases muscle amino acid uptake, decreases adipose tissue fat uptake
→ Cortisol increases the availability of circulating fuel sources in response to physiological stressors. Cortisol impairs skeletal muscle glucose sparing it for the brain) and amino acid uptake (although it promotes hepatic amino acid uptake), and promotes lipolysis from adipocytes. The net effect increases plasma glucose, free fatty acids, and amino acids.
136
4) The hypothalamus secretes which of the following hormones to regulate the pituitary-thyroid axis?
- Corticotropin-releasing hormone (CRH)
- Gonadotropin-releasing hormone (GnRH)
- Thyrotropin-releasing hormone (TRH)
- Growth hormone-releasing hormone (GHRH)
Thyrotropin-releasing hormone (TRH)
→ TRH is released by the hypothalamus and stimulates the anterior pituitary gland to release TSH, which in turn stimulates the thyroid gland to produce thyroid hormones
137
5) The feedback mechanism that regulates thyroid hormone levels primarily involves the inhibition of _________ secretion by the anterior pituitary.
*Fill in the blank*
The feedback mechanism that regulates thyroid hormone levels primarily involves the inhibition of **TSH (thyroid-stimulating hormone)** secretion by the anterior pituitary
→ High concentrations of thyroid hormones inhibit the secretion of TSH from the anterior pituitary, which reduces the stimulation of the thyroid gland
138
Which anterior pituitary cell type produces GH, and what is its target?
Somatotrophs (40–50% of pituitary cells); target is all tissues
139
Where is GHRH released from, and where does it act?
- Neurons in arcuate nucleus of hypothalamus secrete growth hormone-releasing hormone (GHRH) into hypophyseal portal system
- acsts on somatotrophs in the anterior pituitary
140
What intracellular signalling pathway does GHRH activate in somatotrophs?
- GHRH binds to G-protein-coupled receptor on somatotrophs and activates Gαs, which in turn activates adenylyl cyclase
- Increase in cAMP leads to gene transcription & synthesis of GH
141
What hypothalamic hormones regulate GH secretion? (ie what stimulates GH secretion and what inhibits GH secretion)
GHRH stimulates; somatostatin (SST) inhibits
142
What is the role of IGF-1 in GH feedback?
GH stimulates insulin-like growth factor 1 (IGF-I) production → which in turn inhibits GH secretion at both hypothalamic and pituitary levels
(IGF-1 --> produced in liver, plays crucial role in growth/development along with GH & acts as a major mediator of GH-stimultaed somatic growth)
143
What is the role of ghrelin in GH secretion?
the gastric peptide ghrelin is a potent GH secretagogue → enhances hypothalamic GHRH secretion and acts directly on pituitary (acts on somatotroph cells)
144
How do oestrogens and androgens affect GH secretion and action?
- Oestrogens → ↑ GH secretion, ↓ GH receptor signalling in liver
- Androgens → enhance GH peripheral actions
- Exogenous oestrogens → potentiate GH and ghrelin effects
145
How does visceral fat impact GH secretion?
Suppresses GH via ↑ FFA, ↑ insulin, and ↑ free IGF-1.
146
Describe the rhythm of GH secretion
- Pulsatile every 2 hours
- Circadian pattern: highest at night
- Max secretion during slow-wave sleep
(sleep is important for growth!)
147
How does GH secretion vary with sex, puberty, and age?
Higher in women than men
Peaks during puberty
Decreases with age
148
Describe the regulation of GH secretion process.
(ie. hypothalamus --> GH secretion)
1. Hypothalamus:
- Releases GHRH into the hypophyseal portal system (capillary network linking hypothalamus to anterior pituitary)
2. Anterior Pituitary (Somatotrophs):
- GHRH acts directly on somatotrophs to stimulate both synthesis and secretion of GH
3. Pulsatile secretion:
- GH is released in a pulsatile fashion, with secretion influenced by: nutrition, stress, exercise, sleep
4. Peak secretion:
- occurs during puberty → responsible for adolescent growth spurt
149
What does the hypothalamus do in response to hypoglycaemia in terms of GHRH secretion?
secretes GHRH → increases GH to mobilise energy stores
--> GH increases blood glucose by inhibiting glucose uptake in tissues (like muscle and fat) and stimulating glucose production in the liver (gluconeogenesis) + glycogenolysis (further increases blood glucose levels)
150
What are the direct metabolic effects of GH?
- **Adipose tissue** → increases lipolysis → releases fatty acids from adipose tissue → fuels metabolism of other cells in the body
- **Liver** → increases gluconeogenesis and glycogenolysis → increases blood glucose levels
- GH also decreases glucose uptake in muscle and adipose tissue → increases blood glucose levels → contributes to insulin resistance
→ Net effect: ↑ blood glucose and free fatty acids → GH has **diabetogenic effects** in excess.
151
What are the indirect effects of GH (via IGF-1)?
- GH stimulates liver and other tissues to release IGF-1 (somatomedin C) → IGF-1 then binds to IGF-1-like receptors & insulin receptors → promotes cellular metabolism → increases rate of cell division & differentiation throughout the body (ie. cellular metabolism, growth, and repair)
.
Major target tissues:
- Liver → Main site of IGF-1 production
- Bone → Stimulates osteoblast activity → longitudinal bone growth
- Muscle → increases amino acid uptake → increases protein synthesis → muscle hypertrophy/growth
- Kidneys → Modulates renal growth and function
.
Promotes:
- Cell proliferation (mitogenesis)
- Cell differentiation
- Inhibition of apoptosis
152
Where is IGF-1 primarily produced, and what stimulates its release?
Liver; stimulated by GH
153
Negative feedback mechanisms for GH:
- Short loop
- Long loop
Short:
- GHRH inhibits its own secretion from the hypothalamus.
.
Long:
- GH acts on peripheral tissues (liver, bone, muscle) → stimulates production of somatomedins (mainly IGF-1).
- IGF-1 inhibits GH secretion at the anterior pituitary (ie. signals ant. pituitary to stop producing GH)
- Both GH and IGF-1 (somatomedins) stimulate somatostatin (GHIH) release from the hypothalamus → further inhibits GH secretion.
154
What are the effects of GH excess?
- before epiphyseal fusion
- after epiphseal fusion
- Before epiphyseal fusion → **Gigantism**
- After epiphyseal fusion → **Acromegaly**
155
What are the effects of GH deficiency?
- children
- adults
- In children → **Pituitary dwarfism**
- In adults → reduced muscle mass, increased fat mass, fatigue
156
1) Which of the following represents a physiological action of growth hormone?
- Increased breakdown of muscle protein
- Increased utilisation of glucose in the muscle
- Decreased storage of lipids in adipose cells
- Decreased gene transcription
- Decreased gluconeogenesis in the liver
- Decreased storage of lipids in adipose cells
→ GH promotes several metabolic changes. These include a net increase in amino acid uptake in the muscle and liver, a decrease in glucose utilisation and storage, and an increase in lipolysis. The net effect of GH is to decrease glucose and lipid storage in adipose cells.
157
2) Cortisol and growth hormone are most dissimilar in their metabolic effects on which of the following?
- Protein synthesis in muscle
- Glucose uptake in peripheral tissues
- Plasma glucose concentration
- Mobilisation of triglycerides
- Protein synthesis in muscle
→ GH and cortisol have opposite effects on protein synthesis in muscle. GH is anabolic and promotes protein synthesis in most cells of the body, whereas cortisol decreases protein synthesis in extrahepatic cells, including muscle. Both hormones impair glucose uptake in peripheral tissues and therefore tend to increase plasma glucose concentration. Both hormones also mobilise triglycerides from fat stores.
158
Which of the following conditions or hormones would most likely increase growth hormone secretion?
- Hyperglycaemia
- Exercise
- Somatomedin
- Somatostatin
- Ageing
- Exercise
→ Exercise stimulates GH secretion. Hyperglycaemia, somatomedin and the hypothalamic inhibitory hormone somatostatin all inhibit GH secretion. GH secretion also decreases with age
159
What is the typical duration of the menstrual cycle (ovarian/uterine)?
~28 days
160
What are the two main phases of the ovarian cycle, and what separates them?
Follicular phase and luteal phase, separated by ovulation
161
Which phase of the ovarian cycle has a fixed length and how long is it?
The luteal phase is consistently ~14 days long → variation in cycle length is due to the follicular phase
162
Describe the reproductive axis pathway (also called the hypothalamic-pituitary-gonadal (HPG) axis).
1. Hypothalamus → produces GnRH
- GnRH is secreted in a pulsatile manner into the median eminence and delivered to the anterior pituitary via the hypophyseal portal system
2. Anterior pituitary (gonadotrophs) → responds to GnTH by secreting two key gonadotropins
- Luteinising hormone (LH)
- Follicle-stimulating hormone (FSH)
3. Gonads (Testes in males, Ovaries in females) → produce gametes and sex steroid hormones in response to LH and FSH
.
Each gonad contains 3 major types of cells:
- Gametes: males (spermatozoa/sperm), females (oocytes/eggs)
- Secretory cells: males (Leydig cells - secrete testosterone in response to LH), females (secrete androgens and progesterone in response to LH)
- Nurse /support cells: males (Sertoli cells - support sperm maturation), females (Granulosa cells - support oocyte development - convert androgens to oestrogens)
163
What is the mechanism of action of LH and FSH in males?
LH → stimulates Leydig cells to produce testosterone, which...
- Supports spermatogenesis indirectly
- Provides negative feedback to both the hypothalamus and pituitary
.
FSH → stimulates Sertoli cells, which...
- Produce inhibin (negative feedback on FSH)
- Produce androgen-binding protein (ABP), which binds testosterone and maintains high intratubular levels to support spermatogenesis
164
What is the mechanism of action of LH and FSH in males?
LH → stimulates Theca cells to produce androgens, which...
- Are converted to oestrogens in granulosa cells via aromatase
- Also contribute to progesterone synthesis, especially after ovulation
.
FSH → stimulates Granulosa cells, which...
- Support oocyte development and secrete oestrogen
- Later, under LH influence (after LH surge), contribute to progesterone production during the luteal phase
- Secrete inhibin to downregulate FSH
(Note: Granulosa cells are located closely around the oocyte; theca cells form an outer layer)
165
How does hormonal secretion differ in males and females?
- Testosterone, oestrogen, progesterone, and inhibin all exert negative feedback on the hypothalamus and anterior pituitary.
.
In females, hormonal secretion is cyclical:
- Oestrogen can exert **positive feedback** at mid-cycle to trigger the **LH surge** → leading to ovulation
.
In males, secretion is relatively constant (tonic) rather than cyclic
166
The 3 phases of the ovarian cycle are:
- Follicular phase (day 1-14)
- Ovulation (day ~14)
- Luteal phase (day 15-28)
Describe what happens in the follicular phase.
- Begins with menstruation (day 1)
.
Primordial follicles (inactive) begin maturation:
1. Develop into primary follicles
2. Become secondary follicles, forming:
- **Zona pellucida** (protective glycoprotein layer)
- **Theca** **cells** → produce oestrogens
- **Granulosa cells** (some forming the corona radiate)
3. Mature into a Graafian follicle -> dominant follicle ready to release an oocyte (egg) + actively secretes oestrogens
167
The 3 phases of the ovarian cycle are:
- Follicular phase (day 1-14)
- Ovulation (day ~14)
- Luteal phase (day 15-28)
Describe what happens in ovulation
- Triggered by LH surge (due to oestrogen-mediated positive feedback on HPG axis)
.
1. Graafian follicle ruptures
2. Secondary oocyte released into peritoneal cavity -> then swept into fimbriated end of fallopian tube
(note: only one oocyte released per cycle, ovulation typically alternates between ovaries)
168
What is 'Mittelschmerz'?
mid-cycle pain experienced by some women
169
The 3 phases of the ovarian cycle are:
- Follicular phase (day 1-14)
- Ovulation (day ~14)
- Luteal phase (day 15-28)
Describe what happens in the luteal phase.
- Ruptured follicle collapses → forming the corpus luteum (composed of granulosa & theca cells)
- Corpus luteum secretes progesterone mainly → prepares endometrium for implantation
.
- If fertilisation occurs → Corpus luteum persists (maintained by hCG from syncytiotrophoblast)
- If no fertilisation → Corpus luteum degenerates after → forms corpus albicans (scar) + Progesterone and oestrogen levels fall → leads to menstruation
170
The 3 phases of the uterine (endometrial) cycle are:
- Proliferative phase (~ days 5–14)
- Secretory phase (~ days 15–28)
- Menstrual phase (~ days 1–5)
Describe what happens in the proliferative phase.
- Corresponds to the follicular phase of the ovarian cycle
- Begins around day 5, once menstruation ceases
.
Oestrogen from developing follicles stimulates:
- Regeneration of the **stratum functionalis**
- Thickening of the endometrium (to ~2 mm)
- Elongation of glands and growth of spiral arteries
.
Cervical mucus becomes thin and watery → facilitating sperm entry
171
The 3 phases of the uterine (endometrial) cycle are:
- Proliferative phase (~ days 5–14)
- Secretory phase (~ days 15–28)
- Menstrual phase (~ days 1–5)
Describe what happens in the secretory phase.
- Corresponds to the luteal phase of the ovarian cycle.
.
Progesterone from the corpus luteum stimulates:
- Endometrial glands to secrete glycogen-rich substances
- Further thickening of endometrium (~5 mm)
- Coiling and enlargement of spiral arteries
- Transformation of cervical mucus into a thick plug, blocking sperm and pathogens
.
If fertilisation does not occur:
- Corpus luteum degenerates
- Fall in progesterone and oestrogen
- Leads to spiral artery spasm, tissue hypoxia, and lysosomal autolysis
172
The 3 phases of the uterine (endometrial) cycle are:
- Proliferative phase (~ days 5–14)
- Secretory phase (~ days 15–28)
- Menstrual phase (~ days 1–5)
Describe what happens in the menstrual phase.
- Triggered by hormonal withdrawal and ischaemic necrosis of the endometrium.
- Spiral arteries rupture, shedding the stratum functionalis
.
Menstrual flow:
- Duration: 3–6 days
- Volume: ~75 mL (≈50% blood)
- Fibrinolysin released to prevent clotting
.
- Note: Prostaglandins induce uterine contractions, causing dysmenorrhoea in some individuals
173
What does oestrogen do?
- Builds endometrium (proliferative phase)
- Increases LH receptors, triggers LH surge when sustained
- Promote **preparation of the reproductive tract** for fertilisation and implantation.
- Induce **progesterone receptor expression** in target tissues (essential for later response to progesterone)
- ↑ tubal secretion, ↑ cervical mucus, ↑ uterine muscle excitability
- Promotes secondary sexual characteristics
174
What are the effects of progesterone?
- Maintains secretory endometrium (luteal phase) and prepares the body for possible implantation and pregnancy
- Decreases uterine contractions
- Thickens cervical mucus (plug)
- Supports early pregnancy
175
What are the signs of ovulation?
Mittelschmerz (mid-cycle pain), cervical mucus changes, ↑ basal body temperature (progesterone-mediated)
176
How does the combined pill prevent pregnancy?
Maintains negative feedback → suppresses FSH & LH → no ovulation
177
What happens in an anovulatory cycle?
No LH surge → no ovulation → no progesterone → irregular bleeding
178
What causes menstrual cramps?
Prostaglandin-induced uterine contractions
179
Body mass is all about energy in VS energy out.
- Energy in:
- Energy out:
Energy in:
- diet
- insulin
- leptin → related to blood lipid lvls
- ghrelin → related to whether stomach is full or not
.
Energy out:
- basal metabolic rate (ie. amount of energy burned at rest): ~ 2000 calories per day
- activity
thermogenesis (energy we use/burn to store the energy we eat): ~ 10% of calorie intake
180
What did the leptin mouse experiment demonstrate?
- Normal mouse
- Mouse with gene KO (knocked out)
- Mouse with gene KO + injected with serum from normal mouse
1. An equal amount of food was proved to the mice
2. Normal mouse → normal weight
3. Mouse with gene KO → eats lots of food and gets very fat
4. Mouse with gene KO + injected with normal serum → remains normal
→ this gene was found to be leptin
- Leptin is a hormone that lives in our fat (adipose) tissue and goes to our hypothalamus → tells us that we are not hungry (ie. we are full)
.
- Leptin-deficient mice overeat and become obese
- Injection of leptin restores normal feeding behaviour
181
Where is leptin produced and what is its role?
Produced by adipose tissue → acts on the hypothalamus to suppress appetite
182
Which hypothalamic centre is responsible for satiety?
Ventromedial nucleus (VMN)
- Electrical stimulation of this centre elicits sensations of satiety/’fullness’ + inhibits feeding (anorexigenic) responses, even in presence of food
183
Which hypothalamic centre is responsible for hunger?
Lateral hypothalamic area (LHA)
- Electrical stimulation of this centre elicits sensations of hunger and stimulates feeding responses (orexigenic), even after adequate food intake
184
What is the role of the arcuate nucleus?
Integrates hormonal and neural signals → modulates activity of VMN and LHA.
185
What hormone drives the sensation of hunger in the short term & describe the process.
- Driven by **ghrelin**, which is released from stomach during fasting in direct response to **reduced stretch of the stomach**, thus firing of the mechanoreceptors.
- Ghrelin acts at the arcuate nucleus to inhibit and stimulate the neurons which respectively serve both the satiety and hunger centres.
- Levels of ghrelin fall within approximately an hour of food intake.
(In addition, the vagus nerve also has a role: Lack of stomach stretch → vagus nerve → NTS → arcuate nucleus → hunger)
186
What are the main satiety signals in the short term?
- Stomach stretch → vagus nerve → NTS → arcuate nucleus
- Cholecystokinin (CKK) is released from I-cells of small intestine in response to nutrients (e.g. FAs), and influences satiety by action on CCK receptors located in peripheral vagal afferent terminals
- Peptide YY (PYY) and Glucagon-like peptide 1 (GLP1) are co-secreted after a meal, from the L-cells of the distal intestine in proportion to meal size, again with resultant anorexigenic effects at the arcuate nucleus.
- Finally, insulin secretion in response to increased glucose levels acts on the arcuate nucleus in a similar manner to the above peptide hormones
187
What hormone regulates long-term satiety?
- Leptin is secreted by fat cells, with levels increasing proportionally to adipose tissue, to prevent excess.
- Again, leptin receptors are expressed in the appetite-control areas of the brain (arcuate nucleus), and drive anorexigenic responses.
188
What is the effect of insulin on appetite control?
Increases after meals → inhibits hypothalamic hunger signals.
189
What is the effect of leptin on appetite control?
Inhibits hypothalamic hunger signals, representing long-term energy status.
(Note: leptin levels rarely change → leptin lvls are based more on the amount of adipose tissue within the body, rather than blood levels)
190
How does ghrelin signal hunger?
- Ghrelin is released by the stomach when it is empty → ghrelin travels to hypothalamus to tell it that we are hungry
(Empty stomach → ‘growls’ → ghrelin)
191
What are GLP-1 receptor agonists (e.g. semaglutide) used for & how do they work?
- Used to treat obesity and type 2 diabetes
- GLP-1 agonists bind to, and activate, the GLP-1 receptor to increase insulin secretion, suppress glucagon secretion, and slow gastric emptying.
(note: GLP-1 agonists require beta cell function to be effective)
192
Why are GLP-1 agonists effective in weight loss?
(eg. semaglutide/Wegovy)
Mimic satiety hormones (GLP-1) → reduce food intake and support sustained weight loss.
193
A 55-year old female presents with a 3-month week history of progressive hot flushes, palpitations and sweating occurring up to 10 times per day and often making uninterrupted sleep difficult,
Investigations
- serum oestradiol 23 pmol/L (> 100)
- serum follicle-stimulating hormone U/L 87 (<30)
- serum luteinising hormone U/L 110 (<30)
.
Which physiological meditator is predominantly responsible for inducing these symptoms?
- A - dopamine
- B - LHRH
- C- neurokinin B
- D- prostaglandin E2
- E- serotonin
- C- neurokinin B
→ Hypothalamic neurokinin B is the predominant mediator of peri-menopausal flushing
