The Hypothalamus and Pituitary Hormones

The Hypothalamus

• The hypothalamus is a structure in the brain responsible for maintaining homeostasis.
• Regulates endocrine functions, visceral functions, metabolic activities, hunger, thirst, sleep, wakefulness, emotion, sexual function, and more.
• Produces two groups of hormones associated with the posterior and anterior pituitary gland.

Posterior Pituitary Hormones

• Two peptide hormones:
  • Arginine-vasopressin (ADH, antidiuretic hormone)
  • Oxytocin
• Both hormones are synthesized in the hypothalamus and travel to the posterior pituitary through nerve fibers for storage.
• ADH regulates water reabsorption by the kidneys.
• Oxytocin controls milk ejection from the lactating breast and initiates uterine contractions during labor.

Anterior Pituitary Hormones

• Anterior pituitary cells are classified based on staining reactions:
  • Acidophils
  • Basophils
  • Chromophobes

Acidophils

• Two types of cells:
  • Somatotrophs: secrete growth hormone (GH, somatotrophin)
    • Stimulates long bone and soft tissue growth.
    • Influences metabolism of amino acids, fatty acids, and glucose.
    • Secretion is increased by hypoglycemia, stress, and exercise.
    • Regulated by growth hormone releasing hormone (GHRH) and somatostatin from the hypothalamus.
  • Lactotrophs: secrete prolactin
    • Stimulates development and growth of secretory alveoli in the breast and milk production.
    • Inhibits the reproductive system at the gonads and pituitary.
    • Secretion is increased by suckling.
    • Inhibited by dopamine from the hypothalamus.

Basophils

• Three types of cells:
  • Corticotrophs: synthesize pro-opiomelanocortin (POMC), a precursor for multiple hormones:
    • Adrenocorticotrophic hormone (ACTH, corticotrophin): Stimulates adrenal cortex steroid synthesis and secretion.
      • Secretion is increased by stress and has a diurnal rhythm.
      • Regulated by corticotrophin releasing hormone (CRH) from the hypothalamus.
      • Inhibited by glucocorticoid negative feedback.
    • Melanocyte stimulating hormone (MSH): Stimulates skin pigmentation by increasing melanin production.
    • β-Lipotrophin: Converted to endorphins, which have opiate-like effects and help control pain.
  • Gonadotrophs: secrete gonadotrophins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), which act on the gonads.
    • LH and FSH control growth and development of germ cells in the gonads.
    • Also regulate sex hormone (testosterone, estrogen, progesterone) synthesis and secretion.
    • Released stimulated by gonadotrophin releasing hormone (GnRH).
    • Inhibited by sex steroid negative feedback.
  • Thyrotrophs: secrete thyroid-stimulating hormone (TSH, thyrotrophin), which acts on the thyroid gland.
    • Stimulates thyroid hormone (T3 and T4) production.
    • Increases iodine uptake by the thyroid.
    • Stimulates thyroid growth.
    • Released stimulated by thyrotrophin releasing hormone (TRH) from the hypothalamus.
    • Secretion of TRH is stimulated by stress through the CNS.
    • Inhibited by T3 and T4 negative feedback.

Chromophobes

• Once thought to be inactive, but they do contain secretory granules.
• Chromophobe adenomas often secrete hormones, particularly prolactin.

Hypopituitarism

• Deficiency of pituitary hormone production caused by disorders affecting the hypothalamus, pituitary, or surrounding structures.
• Clinical features are usually absent until 70% of the gland is destroyed, unless associated with hyperprolactinemia.
• Can affect all or only a portion of pituitary hormones.
• Causes include tumors, infections (tuberculosis, meningitis, syphilis), infiltrations, head injury, and others.

Consequences of Pituitary Hormone Deficiencies

• Progressive pituitary damage usually presents with deficiencies of gonadotrophins and GH.
• ACTH and/or TSH may remain normal or become deficient later.
• Clinical and biochemical consequences of target-gland failure include:
  • Growth retardation in children due to GH deficiency.
  • Secondary hypogonadism due to gonadotrophin deficiency: Amenorrhea, infertility, atrophy of secondary sexual characteristics, loss of axillary and pubic hair, impotence, or loss of libido.
  • Secondary adrenocortical hypofunction (ACTH deficiency): Hypotension and increased insulin sensitivity with fasting hypoglycemia.
  • Secondary hypothyroidism (TSH deficiency): Clinically indistinguishable from primary hypothyroidism.
  • Prolactin deficiency: Failure to lactate, may occur after postpartum pituitary infarction (Sheehan's syndrome).

Investigation of Suspected Hypopituitarism

• Deficiency of pituitary hormones causes hypofunction of target endocrine glands.
• Investigation aims to confirm deficiency, exclude target gland disease, and assess pituitary hormone secretion after stimulation.
• Measurements include:
  • LH, FSH, and estradiol (female) or testosterone (male)
  • Total or free T4 and TSH
  • Prolactin
  • Cortisol at 09.00 h, to assess adrenocortical insufficiency
• If a target gland hormone is low and the trophic hormone is high, investigate the target gland.
• If both the target gland and trophic hormones are low or low-normal, consider a pituitary stimulation test.
• CT or MRI scans of the pituitary region may help identify the cause of hypopituitarism.
• Combined pituitary stimulation tests (using insulin or glucagon, TRH, and GnRH) can evaluate pituitary hormones.

Insulin Stimulation Test

• Potentially dangerous, must be done under medical supervision.
• Indications:
  • Assessment of GH in growth deficiency.
  • Assessment of ACTH/cortisol reserve.
  • Differentiation of Cushing's syndrome from pseudo-Cushing's syndrome.
• After overnight fast, an intravenous cannula is inserted.
• Basal samples for cortisol, GH, and glucose are collected.
• Soluble insulin is injected to lower blood glucose below 2.5 mmol/L.
• Blood samples are taken at intervals for cortisol, GH, and glucose assays.
• An adequate response includes a cortisol increase of more than 200 nmol/L and exceeding 580 nmol/L, and a GH response greater than 20 mU/L.

Glucagon Stimulation Test

• Used if insulin stimulation test is contraindicated.
• Must be performed in a specialist unit by experienced staff.
• Glucagon stimulates GH and ACTH release, probably via a hypothalamic route.
• Patients fast overnight.
• An intravenous cannula is inserted.

Explore the crucial roles of the hypothalamus and its regulation of various bodily functions through its hormones. This quiz covers the synthesis and functions of posterior and anterior pituitary hormones, including oxytocin and ADH. Test your knowledge on the endocrine system and its components.