Pituitary anatomy and physiology

Figure 11.2 The blood supply of the pituitary gland and its vascular connections with the hypothalamus.

Mechanism of action

Binding of GH to its plasma membrane receptor (mostly in the liver) leads to receptor dimerization. This is followed by a phosphorylation cascade mediated by Janus kinase (JAK) and components of the signal transduction and activators of transcription (STAT) family, which translocate to the nucleus and regulate target gene expression.

Figure 11.3 The embryological origin of the two parts of the pituitary gland.

Regulation of secretion

GH secretion is stimulated by hypothalamic GH-releasing hormone, which acts via a G-protein-coupled receptor and increases cyclic AMP levels. Other factors that may stimulate GH release include stress, exercise, sleep, prolonged fasting and ghrelin (a gastric derived peptide). GH secretion is inhibited by IGF-1 (negative feedback) and hypothalamic somatostatin. GH secretion is pulsatile (6–10 pulses separated by long periods during which GH may be undetectable).

Prolactin

Prolactin is a protein with 198 amino acids, three disulphide bonds and a molecular weight of about 22 kDa.

Effects

Prolactin stimulates the proliferation of the breast lobulo-alveolar epithelium and lactation. It also decreases reproductive function by suppressing gonadotrophin-releasing hormone (GnRH) and pituitary gonadotrophin secretion, and by impairing gonadal steroidogenesis in both males and females.

Mechanism of action

Binding of prolactin to its plasma membrane receptor leads to receptor dimerization. This is followed by a phosphorylation cascade mediated by JAK and components of the STAT family, which translocate to the nucleus and regulate target gene expression.

Regulation of secretion

Prolactin secretion is inhibited by hypothalamic dopamine binding to D₂ receptors. Prolactin secretion is stimulated by hypothalamic thyrotrophin-releasing hormone (TRH) and other factors including oestrogen, opiates, serotonin and acetylcholine. Prolactin levels may be higher in stress, during sleep and following a suckling stimulus, exercise, meals, sexual intercourse and an epileptic fit.

Prolactin secretion is pulsatile, with the highest secretory peaks occurring during rapid eye movement sleep. Peak serum levels occur between 4 and 6 a.m.

ACTH

ACTH is a peptide with 39 amino acids and a molecular weight of 4.5 kDa. ACTH, melanocyte-stimulating hormone and endorphins are products of the same gene: POMC (proopiomelanocortin).

Effects

ACTH stimulates the conversion of cholesterol to pregnenolone in the zona fasciculata and reticularis, and therefore stimulates the production of cortisol and adrenal androgens.

Mechanism of action

Binding of ACTH to its plasma membrane receptor in the zona fasciculata of the adrenal gland results in the activation of adenylate cyclase and increased cyclic AMP production. This leads to the stimulation of steroidogenic acute regulatory protein (StAR), which mediates the transport of cholesterol through the cytosol to the inner mitochondrial membrane, where it is converted to pregnenolone. This is the rate-limiting step in cortisol synthesis. The activation of adenylate cyclase also results in the upregulated gene expression of other enzymes involved in steroid synthesis.