1. Hypothalamus and pituitary gland

Outline the anatomy of the pituitary & the hypothalamus.

How does the hypothalamus control the anterior & posterior pituitary?

• Anterior: ventral hypothalamus → hormones via portal veins → anterior pituitary → hormone release

• Posterior: supraoptic & paraventricular nuclei → axons → posterior pituitary → release oxytocin & ADH

• Act as separate endocrine glands

What hormones does the hypothalamus release to control the pituitary?

• Hormones that influence the anterior pituitary:

  • GnRH – Gonadotropin-releasing hormone

  • CRH – Corticotropin-releasing hormone

  • TRH – Thyrotrophin-releasing hormone

  • TRH/Dopamine – Prolactin releasing/inhibiting factors

  • GHRH – Growth hormone releasing hormone

  • Somatostatin – Growth hormone release inhibiting hormone

• Hormones that influence the posterior pituitary:

  • Vasopressin or antidiuretic hormone (ADH) or arginine vasopressin (AVP)

  • Oxytocin

What are the six principal hormones secreted by the anterior pituitary & their target organs?

• FSH/LH – Follicle-stimulating hormone / Luteinizing hormone → Gonads

• ACTH – Adrenocorticotrophic hormone → Adrenal gland

• TSH – Thyroid-stimulating hormone → Thyroid gland

• PRL – Prolactin → Mammary gland

• GH – Growth hormone → Bone, soft tissue, viscera

• Mnemonic: FLAT PG – helps remember the hormones

How are FSH & LH regulated, and what are the effects of their dysregulation?

• FSH & LH are secreted by anterior pituitary → act on gonads (ovaries/testes)

• Ovaries → oestrogen; testes → testosterone (from Leydig cells)

• ↑ Oestrogen/testosterone →

  • Direct negative feedback on anterior pituitary

  • Indirect negative feedback on hypothalamus (↓ GnRH)

• GnRH is secreted in a pulsatile manner → regulates FSH & LH

• Inhibin (from gonads) → directly inhibits FSH secretion

• Hyposecretion (↓ oestrogen/testosterone) → amenorrhoea, sterility, delayed puberty

• Hypersecretion (↑ oestrogen/testosterone) → premature sexual development in children

What are synthetic gonadorelin, GnRH analogues (e.g. buserelin, goserelin) & danazol used to treat & how do they work?

• Infertility (alternative: recombinant LH & FSH injection)

• Amenorrhoea (lack of menstruation)

• Androgen-dependent prostatic cancer

• Endometriosis

• Precocious puberty

What does ACTH do & what are the effects of its hypo- & hypersecretion?

• ACTH (Adrenocorticotrophic hormone) is secreted by the anterior pituitary

• Stimulated by CRH from the hypothalamus

• Acts on adrenal glands → ↑ secretion of cortisol (a glucocorticoid) & some sex hormones

• Cortisol provides:

  • Direct negative feedback to ACTH

  • Indirect negative feedback to CRH

• Secretion ↑ during stress (pain, fear, hypoglycaemia)

• Hyposecretion → Addison’s disease

• Hypersecretion → Cushing’s syndrome/disease

What does TSH do & what are the effects of its hypo- & hypersecretion?

• TSH (Thyroid-stimulating hormone) is secreted by the anterior pituitary

• Stimulates thyroid follicular cells → secrete T₄ (thyroxine) & T₃ (triiodothyronine)

• T₃ & T₄ give direct negative feedback to the pituitary (not the hypothalamus)

• Hyposecretion → cretinism (in infants) or hypothyroidism

• Hypersecretion → Graves’ disease (autoimmune hyperthyroidism)

What are the roles of prolactin & effects of its hypo- & hypersecretion?

• From anterior pituitary → breast development & milk production

• Inhibited by dopamine

• ↑ in pregnancy & suckling

• Hyposecretion → no lactation

• Hypersecretion (e.g. tumour) → infertility, ↓ libido, galactorrhoea, breast enlargement, headaches

• Treatment: dopamine agonists, surgery, radiotherapy

• GH → acts on bone, cartilage, tissues; indirect effects via IGF from liver/kidneys

• Regulated by GHRH (+) & somatostatin (−) from hypothalamus

• GH inhibits insulin (diabetogenic effect)

• Hyposecretion (childhood) → dwarfism (treat with GH)

• Hypersecretion:

  • Pre-puberty → gigantism

  • Post-puberty → acromegaly

What causes acromegaly & what are its signs and symptoms?

• Caused by post-puberty GH excess, usually from pituitary adenoma (>1 cm)

• Enlarged hands, feet, heart, kidneys

• Coarse facial features: large nose, jaw, lips, tongue; spaced teeth

• Skin outgrowths, ↑ sweating

• Voice changes, snoring, sleep apnoea

• Carpal tunnel (tingling/numb fingers)

• Hypertension, fatigue, ↑ blood glucose → diabetes

• Headaches, vision changes

How is acromegaly treated?

• Surgery to remove pituitary tumour

• Somatostatin analogues (octreotide, lanreotide)

• GH blocker (pegvisomant)

• Radiotherapy

• Dopamine agonists (bromocriptine, cabergoline) (tumours often express D2-dopamine receptors)

How do the hypothalamus and pituitary gland work together?

• Hypothalamus hormones regulate pituitary hormone secretion

• Anterior & posterior pituitary lobes function as separate endocrine glands

What regulates ADH release?

• Hypothalamic osmoreceptors detect increased OP, and baroreceptors detect decreased BP.

• Stimuli like severe pain, fear, nausea, anaesthesia, and some drugs increase ADH release.

• Alcohol inhibits ADH release.

• ADH causes vasoconstriction, increases water reabsorption in the kidneys, and raises BP and blood volume.

What causes & treats Diabetes Insipidus?

• Caused by hyposecretion of AVP (Arginine Vasopressin), leading to large amounts of dilute urine & increased blood Na+ concentration.

• Symptoms: polydipsia (excessive thirst) and polyuria (excessive urination).

• Treatment: synthetic vasopressin or vasopressin analogues like desmopressin (Desmospray).

What causes and treats hypersecretion of AVP in Schwartz-Bartter syndrome?

• Caused by small cell lung carcinoma, leading to excessive water retention, low plasma sodium, and high urine osmolarity.

• Treatment: tumor removal or AVP antagonist (demeclocycline).

How does ADH (AVP) work, and what happens when blocked by an antagonist?

• ADH binds to a receptor, activating G proteins and increasing cyclic AMP. This activates protein kinase A, which stimulates water reabsorption.

• If blocked by an AVP antagonist, this process is inhibited, leading to symptoms like in Schwartz-Bartter syndrome.

How does oxytocin work during childbirth and breastfeeding?

• Nipple suckling and uterine contractions trigger the release of oxytocin from the posterior pituitary.

• Oxytocin stimulates uterine contractions (during labor) and milk ejection (during breastfeeding).

• This creates a positive feedback loop, as contractions and suckling continue to trigger more oxytocin release.