Endocrinology: Physiology - Hypothalamic and pituitary function Flashcards
What is the hypothalamus (structurally)?
Anterior end of diencephalon lying below hypothalamic sulcus, in front of interpeduncular nuclei
How does the hypothalamus communicate with the anterior pituitary?
Via vascular connections (portal hypophysial vessels)
How does the hypothalamus communicate with the posterior pituitary?
Via neural connections
Where do the anterior and posterior pituitary arise from embryologically?
Anterior: pouch of Rathke (evagination from roof of pharynx)
Posterior: evagination of floor of third ventricle
What type of tissue composes most of the posterior pituitary?
Made up in large of axon endings arising from cell bodies in the supraoptic and paraventricular nuclei, and passing to the posterior pituitary via the hypothalamohypophysial tract
What hormones are secreted by the posterior pituitary?
Vasopressin
Oxytocin
What hormones are secreted by the anterior pituitary?
TSH
ACTH
FSH
LH
Prolactin
GH
Five regulatory functions of the hypothalamus
- Temperature regulation
- Neuroendocrine control
- Appetite behaviours
- Defensive reactions (fear, rage)
- Control of body rhythms
Eight hormones under neuroendocrine control of the hypothalamus
- Catecholamines
- Vasopressin
- Oxytocin
- TSH via TRH
- ACTH and B-LPH via CRH
- GH via somatostatin and GRH
- FSH and LH via GnRH
- Prolactin via PRH and PIH
What three “appetitive behaviours” are under hypothalamic control?
- Thirst
- Hunger
- Sexual behaviour
In what three organs is vasopressin produced?
CNS
Gonads
Adrenal cortex
In what two organs is oxytocin produced?
CNS
Thymus
What is the effect of hypothalamic control on prolactin secretion?
Predominantly inhibitory
What are the two physiologic effects of oxytocin?
- Induce contraction of myoepithelial cells lining breast ducts to induce milk ejection
- Induce contraction of uterine smooth muscle (enhanced by oestrogen, inhibited by progesterone) -> role in labour
Six hypophysiotropic hormones
- TRH
- CRH
- GnRH
- GRH
- Somatostatin
- PIH
(postulated that PRH also exists)
From what part of the hypothalamus are the hypophysiotropic hormones secreted?
Median eminence
What pituitary hormones are released in response to TRH?
TSH
Prolactin
Release of which two pituitary hormones is inhibited by somatostatin?
TSH
GH
What is the function of B-LPH?
Unknown
What is Kallmann syndrome?
Congenital abnormality in the olfactory pathways which prevents the normal migration of GnRH neurons up the olfactory nerve
Presents as hypogonadotropic hypogonadism and anosmia
What is the normal morning oral temperature and how does this change throughout the day?
Normal morning oral temperature 36.3-37.1°C
Regular circadian fluctuation of 0.5-0.7°C
Lowest at 0600, highest in the evenings
What is the temperature of the scrotum?
Tightly regulated at 32°C
What is the relationship between rectal, oral and core temperature?
Rectal reflects core
Oral 0.5°C lower than rectal
What is the difference in basal temperature between children and adults?
Children typically 0.5°C higher
What happens to basal temperature during ovulation?
Increases
What are the three main mechanisms of heat production, and which is the major source of heat?
- Muscular activity (major heat source)
- Food intake
- Basic metabolic processes
What are the four main mechanisms of heat loss and what % does each account for at 21°C?
- Radiation and conduction (70%)
- Vaporisation of sweat (27%)
- Respiratory (2%)
- Urination and defecation (1%)
Which part of the pituitary regulates the response to heat, and which to cold?
Anterior pituitary responds to heat
Posterior pituitary responds to cold
Five afferents to hypothalamus for body temperature information
- Skin
- Deep tissues
- Spinal cord
- Extrahypothalamic brain
- Hypothalamus itself
What are the temperature thresholds for different temperature-regulating responses?
37°C: sweating, vasodilation
36.8°C: vasoconstriction
36°C: non-shivering, thermogenesis
35.5°C: shivering
At what body temperature is the ability to spontaneously return temperature to normal lost?
28°C
What body temperatures are survivable without permanent ill effects?
21-24°C
Five secretory cell types in the anterior pituitary by percentage. What other cell types are in the pituitary?
Secretory cells:
1. Somatotropes (50%)
2. Lactotropes (10-30%)
3. Gonadotropes (20%)
4. Corticotropes (10%)
5. Thyrotropes (5%)
Others:
1. Folliculostellate cells (regulate growth and function of secretory cells
2. Pluripotent stems cell (responsible for pituitary plasticity over lifetime)
How much of growth hormone circulates in bound form?
50%
Normal plasma level of growth hormone (bound and unbound)
<3ng/dL
Half-life of GH
6-20mins
Where is growth hormone metabolised?
Liver
What type of receptor is the growth hormone receptor?
Cytokine receptor (extracellular, transmembrane, and intracellular portions -> downstream intracellular signalling cascade)
Seven direct and four indirect effects of growth hormone
Direct:
1. Increased Ca+ intestinal absorption
2. Na+/K+ retention
3. Lipolysis (increased free fatty acids)
4. Protein synthesis (increased PO43-, decreased Ur and AAs)
5. Decreased sensitivity to insulin
6. Epiphysial growth
7. IGF-1 release
Indirect via IGF-1:
1. Antilipolytic activity
2. Insulin-like activity
3. Protein synthesis
4. Epiphysial growth
What are the effects of GH-stimulated increased protein synthesis on biochemistry?
Increased phosphate and nitrogen balance
Decreased blood urea nitrogen and circulating amino acids
What is the role of IGF-II?
Somatomedin which regulates growth during foetal development
Describe the feedback control seen with GH
GH inhibits GRH release from hypothalamus
IGF-1 inhibits GH release from anterior pituitary, and stimulates somatostatin release from hypothalamus
What broad groups of factors increase GH secretion?
- Actual or threatened decrease in substrate available for intracellular energy production
- Conditions in which certain amino acids are increased
- Stressful stimuli
- Certain hormones
Fifteen factors which stimulate growth hormone secretion
- Hypoglycaemia
- 2-deoxyglucose
- Fasting
- Exercise
- Going to sleep
- Increase in certain AAs (e.g. Arginine)
- Protein meal
- Ghrelin
- Glucagon
- Vasopressin
- Oestrogens and androgens
- L-Dopa and a-adrenergic agonists
- Dopamine receptor agonists
- Stressful stimuli
- Pyrogens
Six factors which inhibit growth hormone secretion
- Glucose
- FFAs
- REM sleep
- Cortisol
- Medroxyprogesterone
- GH and IGF-1
Half-life of FSH
170mins
Half-life of LH
60mins
Half-life of prolactin
20mins
What is prolactin inhibiting hormone?
Dopamine
What type of receptors are FSH and LH receptors?
GPCRs
What kind of receptor is the prolactin receptor?
Cytokine receptor
Two effects of FSH
- Stimulate Sertoli cells in testes to maintain spermatogenic epithelium
- Early growth of ovarian follicle
Five effects of LH
- Tropic for Leydig cells (produce testosterone in testes)
- Maturation of ovarian follicles and oestrogen secretion from them
- Initial formation of corpus luteum
- Progesterone secretion
- Ovulation
What is the effect of prolactin on FSH/LH?
Inhibits
Prevents ovulation
Five factors that increase prolactin secretion
- Exercise
- Stress
- Nipple stimulation
- Pregnancy (peaks at parturition)
- Chlorpromazine and other dopamine receptor blockers
Two factors that decrease prolactin secretion
- L-dopa and dopamine agonists (e.g. bromocriptine)
- Prolactin (negative feedback loop)
What is Sheehan syndrome?
Hypopituitarism caused by pituitary infarct and necrosis as a result of shock secondary to massive postpartum haemorrhage
Vascular supply to anterior pituitary is already vulnerable, and moreso in pregnancy as the pituitary is enlarged
Three causes of hypopituitarism?
- Infarct (e.g. Sheehan syndrome)
- Tumour
- Suprasellar cyst (compression)
