Hypothalamic-Pituitary Relationships and Hormones

Hypothalamic-Pituitary Relationships

• The pituitary gland, also known as the hypophysis, is connected to the hypothalamus by the pituitary stalk (infundibulum).
• The pituitary has two main distinct portions: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis).
• A relatively avascular zone called the pars intermedia lies between these two portions.

Anterior Pituitary Hormones

• The anterior pituitary is primarily a collection of endocrine cells.
• Six peptide hormones are secreted: Thyroid-stimulating hormone (TSH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Growth hormone (GH), Prolactin (PRL), and Adrenocorticotropic hormone (ACTH).
• Hormones are stored in membrane-bound secretory granules.
• Release is stimulated by hypothalamic-releasing hormones or release-inhibiting hormones.
• Hormones are organized into families based on structural/functional homology.
  • TSH, FSH, and LH form one family.
  • ACTH forms a second family.
  • GH and PRL constitute a third family.
• Hormones of the ACTH family are derived from a single precursor, pro-opiomelanocortin (POMC).

Growth Hormone (GH)

• GH is synthesized in somatotrophs of the anterior pituitary. Also called somatotropin or somatotropic hormone.
• GH secretion follows a pulsatile pattern, with bursts occurring approximately every 2 hours, with the largest burst occurring within 1 hour of falling asleep.
• During childhood GH secretion is relatively stable.
• A significant surge occurs during puberty due to estrogen in females and testosterone in males.
• Secretion is controlled by two pathways from hypothalamus.
  • Stimulatory - GHRH.
  • Inhibitory - Somatostatin (SRIF)
• Regulation by negative feedback loops:
  • GHRH inhibits its own secretion (ultrashort-loop).
  • Somatomedins (IGFs) from target tissues inhibit GH secretion
  • GH and somatomedins stimulate somatostatin secretion from the hypothalamus.

Actions of GH

• Some of GH’s effects are direct on target tissues (skeletal muscle, liver, and adipose tissue).
• These direct actions are mediated by tyrosine kinase-associated receptors.
• Other actions are mediated indirectly through the production of somatomedins in the liver (e.g., somatomedin C).
• Somatomedins act through IGF receptors.
• GH has a diabetogenic effect (impairing insulin's effects).
• GH stimulates protein synthesis, and increases linear growth.

Pathophysiology of GH

• GH deficiency results in short stature, mild obesity, and delayed puberty in children.
• GH excess results in acromegaly (before puberty it causes gigantism.)
• Treatments for GH disorders involve using somatostatin analogs like octreotide.

Prolactin (PRL)

• PRL is the major hormone responsible for lactogenesis (milk production).
• It participates in breast development along with estrogen.
• PRL secretion is tonically inhibited by dopamine (also called prolactin-inhibiting factor [PIF]).
• TRH increases PRL secretion
• PRL inhibits its own secretion (negative feedback) by stimulating dopamine release from the hypothalamus.
• Pregnancy and breast-feeding are significant stimuli for PRL secretion.

Actions of PRL

• PRL stimulates milk production in the breast (in cases such as casein and lactalbumin).
• PRL is necessary for breast development from estrogens.
• PRL inhibits ovulation by decreasing synthesis and release of GnRH.
• PRL inhibits spermatogenesis by decreasing the synthesis of GnRH.

Posterior Pituitary Hormones

• ADH is made in the supraoptic nuclei.
• Oxytocin is made in the paraventricular nuclei.
• ADH (also called vasopressin) affects kidneys and blood vessels.
• Oxytocin influences the breast and uterus.

ADH (Antidiuretic Hormone)

• ADH causes the kidneys to decrease water excretion (antidiuresis.
• ADH increases H2O permeability in the late distal tubule and collecting duct (via V2 receptor).
• ADH causes vascular smooth muscle contraction (via V1 receptor).
• Factors affecting ADH secretion include increased serum osmolarity, decreased ECF volume, pain, nausea, and more.

Central Diabetes Insipidus

• Caused by failure of the posterior pituitary to secrete ADH.
• Results in large volumes of dilute urine, and serum that is too concentrated (e.g., increased Na+ concentration).
• Treated with ADH analogues.

Nephrogenic Diabetes Insipidus

• Defect in the ability of the collecting ducts' principal cells to respond to ADH.
• Results in large volumes of dilute urine, and increased serum osmolarity.
• Treated with thiazide diuretics.

Syndrome of Inappropriate ADH (SIADH)

• Autonomous secretion of ADH not regulated appropriately from an autonomous site.
• Results in excess water reabsorption and too much diluted body fluid.
• Urine is inappropriately concentrated.
• Treatable with antagonists of ADH or water restriction.

Oxytocin

• Oxytocin stimulates milk expression from breast alveoli into ducts.
• Oxytocin causes contraction of the myoepithelial cells in the breast.
• Oxytocin causes uterine contraction during pregnancy.
• Oxytocin can be used to induce labor.