Endocrine Flashcards
What functions does the hypothalamic-pituitary axis regulate?
Regulates the functions of; thyroid, adrenal, osmoregulation, reproductive glands, growth and milk production and secretion
Describe the structure of the pituitary and what is the other name?
Hypophysis, consists of an anterior (adenohypophysis) and a posterior (neurohypophysis) lobe. The hypothalamus is connected to the pituitary by a thin stalk called infundibulum
What tissue makes up the posterior pituitary? What does this secrete and where do they act?
The neurohypophysis is made of neural tissue. The posterior pituitary is a collection of axons, whose bodies are in the hypothalamus. This secretes neuropeptides (as they are secreted from nerve cells) anti-diuretic hormone (acts on kidney and arterioles) and oxytocin (Brest and uterus).
What tissue makes up the posterior pituitary? What does this secrete and where do they act?
The neurohypophysis is made of neural tissue. The posterior pituitary is a collection of axons, whose bodies are in the hypothalamus. This secretes neuropeptides (as they are secreted from nerve cells) anti-diuretic hormone (acts on kidney and arterioles) and oxytocin (Brest and uterus).
Where are the cell bodies of the neurons which secrete ADH and oxytocin located ?
The cell bodies are located in the supraotic and paraventricular nuclei of the hypothalamus. The neuropeptide hormones are produced by both, but ADH is mainly secreted by supraoptic while oxytocin by the paraventricular nuclei
What is the adenohypophysis, what tissue is it made of and why?
It is the anterior pituitary and it is made of endocrine cells - the gland derives from the primitive foregut, hence the endocrine cells
What is the adenohypophysis, what tissue is it made of and why?
It is the anterior pituitary and it is made of endocrine cells - the gland derives from the primitive foregut, hence the endocrine cells
What 7 hormones does the anterior pituitary secrete?
1) thyroid stimulating hormone (tsh)
2) follicular stimulating hormone (fsh)
3) leutenising hormone (LH)
4) growth hormone
5) prolactin
6)adenocorticotroic hormone ACTH)
7) melanocyte stimulating hormone
How do the hypothalamus and anterior pituitary communicate ?
In both neuronal and endocrine manner. They are linked by the hypothalamic-hypophyseal portal blood vessels
Why does the hypothalamus have its own portal venous system?
The hypophyseal portal vessels allow the hypothalamus to communicate directly with the anterior pituitary. This allows it to;
1) release high concentrations of hypothalamic hormones that are delivered directly to the anterior pituitary
2) the hypothalamic hormones are isolated from the systemic circulation
What is the the TRH-TSH-thyroid system
thyroid releasing hormone (trh) is released from the hypothalamus-> secreted into the hypothalamic-hypophyseal portal vessels -> reaches anterior pituitary and stimulated thyroid stimulating hormone secretion (tsh) -> tsh enters systemic circulation and delivered to thyroid gland -> T3 released
Of the 6 anterior pituitary hormones, which are secreted by the same cell type? Which one is it?
What are the other cell types the secrete the other hormones ?
FSH and LH are both secreted by gonadotrophs
TSH - Thurotrophs
ACTH- corticotrophs
GH- somatotrophs
Prolactin - lactotrophs
What are pituitary hormone families ? Which ones are there
Hormones of the anterior lobe are organised in families based on their structural and functional homology.
1)TSH, FSH and LH family
2) acth family
3) GH and prolactin are a family
Define the structure of the FSH, LH and TSH family ?
They are composed of alpha and beta subunits. The alpha are all the same and transcribed from the same gene -> inactive component. The beta subunit is different and is the active unit . These are glycoproteins
What are POMC
Pro-opiomelanocortin; this is the common precursor for the hormones in the ACTH (anterior pituitary ) family
What hormones are included in the acth family ?
ACTH, Gama and beta lipoprotein, beta-endorphin, and melanocyte stimulating hormone
What is somatotropin ?
This is growth hormone. Growth hormone is synthesised by somatotrophs of the anterior pituitary
What allows for the synthesis of growth hormone?
Growth hormone releasing hormone (GHRH) is released from the hypothalamus (hypothalamic releasing hormone) which results in growth hormone release from the anterior pituitary
What is the pulsatile release of growth hormone and how does this change through life?
GH is released throughout life in pulses every 2 hours. The biggest pulse is 1h post falling asleep.
GH release increases in early childhood. There is a massive release in puberty, induced in females by oestrogen and in males by testosterone. These the decline throughout adult hood
What are potent inhibitors of growth hormone release suppression ?
Hypoglycaemia and starvation
Draw the regulation of growth hormone secretion pathway
What controls release of growth hormone and how
The hypothalamus has two pathways which control release;
1) growth hormone releasing hormone (ghrh)
2) somatostatin
Ghrh acts on somatotrophs of the anterior pituitary and stimulate synthesis and secretion of GH
Somatostatin is released by the hypothalamus and acts on the anterior pituitary to inhibit growth hormone release
What negative feedback mechanism regulate growth hormone release ?
1)GHRH inhibits its own secretion via an ultrashort negative feedback loop
2) somatomedins (byproduct of GH action) on target tissue inhibit secretion of GH by the anterior pituitary
3) GH and somatomedins stimulate somatostatin release by the hypothalamus
What are the main effects of growth hormone metabolically and what are the key receptors?
Direct effect; skeletal muscle, adipose tissue, liver growth. These are mediated by tyrosine kinase-associated receptors
Indirect; mediated by somatomedins; main role is the production of IGF-1. IGF’s act through intrinsic tyrosine kinases
What are the main actions of growth hormone;
1) diabetogenic or anti-insulin effect-> increased gluconeogenesis in the liver. Lipolysis is also induced. Both increase BG
2)increased protein synthesis; stimulate DNA->RNA->PROT in nearly all organs
3) increased linear growth: alters cartilage metabolism, bone growth etc via protein synthesis
Define growth hormone deficiency;
Children; causes dwarfism, late puberty, mild obesity. Affects every downstream pathway
Adults;
Define growth hormone excess?
Acromegaly: growth hormone decreasing adenoma.
If before puberty-> giganteism due to excess linear growth at the physeal plate
After puberty-> once bone plates have closed and linear growth is not possible we see organomegally, tongue, hand and foot growth, insulin resistance and glucose intolerance
What is the role of prolactin and what concentration level is it found at
Development of breasts, inhibition of ovulation and stimulation of milk production. Low levels in males and non preganant females. Pregnancy causes a surge
Describe the synthesis of ADH and oxytocin
Neuropeptides produced in the posterior pituitary and are synthesised in the supraoptic (ADH neurons) and paraventricular nuclei (oxytocin) of the hypothalamus. Each produces the other hormone but to a lesser concentration. Synthesised as pre-prohormones, which are converted to progormones in the golgi in the hypothalamus. These are packed into vesicles that travel down the axons to the posterior pituitary where they are cleaved into the hormones
How are neuropeptides of the posterior pituitary secreted
When an action potential travels down the body to the axon in the posterior pituitary
What is the response of the posterior pituitary to an increase in serum osmolarity
Increased osmolarity (decreased water content) the anterior pituidary secretes and to diuretic hormone
What is the function of ADH?
ADH acts on the principal cells of the late distal tubule and collecting duct to increase water absorbtion, thus decreasing osmolarity
What is another name for ADH?
Vasopressin
What are the 9 stimulators factors for ADH?
1) Increased serum osmolarity
2) decreased ECF
3) angiotensin II
4) pain
5) Nausea
6) hypoglycaemia
7) Nicotine
8) Opiates
9) antineoplastic drugs
What are the 4 inhibitors of ADH ?
1) Decreased serum osmolarity
2) ethanol
3) alpha adrenergic agonist
4) ANP
How is ADH secreted in response to serum osmolarity?
Increased osmolarity -> sensed by baroreceptors in the anterior hypothalamus -> action potentials initiated in cell body of the ADH neurons -> depolarisation wave propagates down the nerves to the posterior pituitary-> posterior pituitary releases ADH
How is ADH released in response to hypovolemia or ECF volume contraction
Decrease of ECF by >10% results in BP drop sensed by baroreceptors of the left atrium, carotid artery and aortic arch->the vagus communicates this to the hypothalamus-> results in ADH increase
What are the actions of ADH?
1) increase in water permeability of the principal cells of the late distal tubules and collecting ducts
- ADH binds V2 receptor->adenylate cyclase (via Gs GPCR)->cAMP ->upregulated aquaporin 2 (AQP2) deposition in the membrane
2) contraction of vascular smooth muscle (hence name vasopressin).
- ADH-> V1 receptor-> phospholipase C (via Gq protein) -> IP/Ca2+ -> vascular smooth muscle contraction.
What are the actions of ADH?
1) increase in water permeability of the principal cells of the late distal tubules and collecting ducts
- ADH binds V2 receptor->adenylate cyclase (via Gs GPCR)->cAMP ->upregulated aquaporin 2 (AQP2) deposition in the membrane
2) contraction of vascular smooth muscle (hence name vasopressin).
- ADH-> V1 receptor-> phospholipase C (via Gq protein) -> IP/Ca2+ -> vascular smooth muscle contraction.
What are the main pathophysiologic changes associated with ADH?
- central diabetes insipidus; failure of the posterior pituitary to secrete ADH -> collecting ducts become impermeable and urine cannot be concentrated -> urine diluted and body fluids become concentrated (hyperNa and osmolarity). ADH levels are low
- nephrogenic diabetes insipidus; principal cells of the collecting duct do not respond to ADH due a defect in V2 recepto, Gs protein or adenylate cyclase. Same effect as above - however, ADH levels are elevated
-syndrome of inappropriate ADH (SIADH); excessive ADH is secreted from an autonomous site (eg Oat cell carcinoma of the lung). Excessive ADH causes excessive water reabsorbtion by collecting duct diluting body fluid (low osmolarity and low Na) and urine is inappropriately concentrated
What are the treatments for ADH pathologies
- central diabetes insipidus; treated with ADH analogue dDAVP
- nephrogenic diabetes insipidus; thiazide diuretics
- inhibit Na reabsorbiton in early distal tubule preventing urine dilution at this site
- decrease GFR (less water filtered, less excreted)
- increase Na excretion cause secondary ECf volume contraction
- SIADH; giving ADH antagonist Demeclocycline or water restriction
What stimulus’s stimulate oxytocin secretion and milk let down ?
Cervix dilation, suckling, smell/sight/sound of the infant,
What are inhibitors of oxytocin ?
Opioids (inc endorphins)
How does suckling result in oxytocin release ?
Sensory receptors in the nipples transmit signals to the spinal cord via afferent neurons. This ascends the spinothalamic tract to the brain stem, and up to the paraventricular nucleus of the hypothalamus
What are the effects of oxytocin release ?
- milk ejection;
Oxytocin ->contraction of the myoepithelial cells lining these ducts forcing the milk into the large duct - uterine contraction
At low concentrations it causes forceful contraction of smooth muscles of the uterus
What are the full names for T3 and T4
T3;triidothyronine
T4; tetraidothyridine or thyroxine
In what percentage is T3 and T4 excreted and which one is the metabolically active ?
90% of what is excreted is T4, although T3 is metabolically active. The T4 is usually converted into the tissues into T3
What is rT3?
Reverse T3 and it has no biological activity
Describe the layout of the cells that produce the cells that produce thyroid hormones
Follicular epithelial cells of the thyroid gland are arranged in follicles. The cells have a basal membrane facing the blood and an apical membrane facing the follicular lumen. The lumen is full of colloid which is composed of newly synthesised thyroid hormones attached to thyroglobulin
What happens when the thyroid gland is stimulated ?
The colloidal hormone is absorbed into the lumen by endocytosis
