The anterior pituitary (adenohypophysis)

The posterior pituitary is part of the brain; the anterior pituitary is not In embryonic development, anterior pituitary arises from Rathke’s Pouch, an outgrowth of the pharynx. Hypothalamic neurons communicate with the anterior pituitary by chemical signals called releasing factors and release inhibiting factors. In almost all cases, these are small peptides.

A P Magnocellular hypothalamic neurons send their axons through the pituitary stalk and form neurohemal synapses in the post. pituitary, releasing small peptide hormones ADH (vasopressin) and oxytocin. Parvocellular neurons in the hypothalamus form neurohemal synapses on capillaries at the base or in the pituitary stalk, releasing factors that stimulate or inhibit release of large peptide or glycopeptide hormones from non- neuronal pituitary cells.

Ant. Pituitary Hormone Releasing hormone(s) Targets tissues/organs Effects/Final Hormones Adrenocortico- trophic H. ACTH CRH (41 aa)Adrenal cortexsecretion of Cort (and Aldo, DHA) Thyroid-stim. H. TSH TRH (3aa)thyroidT 4 =thyroxine – increased basal metabolism Growth H. (somatotropin, GH) GHRH (44aa) GIH = somatostatin (14aa) Whole body, via growth factors Increase in stature and body mass, increased anabolism Metabolism and Growth Hormones

AP hormone Releasing hormone(s) Targets tissues/organs Effects/Final Hormones Follicle-stim. H. FSH GnRH (10aa)Testes, OvariesSpermatogenesis Follicular maturation Luteinizing H. LHGnRHTestes, Ovaries Testosterone Progesterone, Estrogens – 2ndary sex characteristics Prolactin PRLPRLRH=TRH? PIH = dopamine Mammary glands Lactation Reproductive hormones

Feedback control of hormone secretion in the simple system Sensor – regulated variable gland hormone target Simple negative feedback Here, hormone secretion is self-regulated by negative feedback from the target to the gland, and by a short loop in which the gland is sensitive to the hormone it secretes.

The hierarchical structure of ant. pituitary axes makes multiple feedback loops possible hypothalamus Ant. pituitary Target gland Target - effects Releasing factor Tropic hormone Final hormone(s) Not all of these loops are operative in any given system.

The control of cortisol secretion is an example hypothalamus corticotrophs Adrenal cortex cortisol CRF ACTH

Hormone levels are diagnostic for location of a lesion in the hierarchy Example 1: hypopituitary dwarfism vs Laron dwarfism: –Hypopituitary: hGH levels low, IGFs (insulin- like groth factors or somatomedins) low: hypothalamus or pituitary is at fault –Laron: hGH levels are high; IGFs low; liver fails to respond to hGH: GH receptor is at fault

Example 2: Cushing’s Disease vs Cushing’s Syndrome Cushing’s Disease: hyperpituitary hyperadrenalism: ACTH levels elevated; excess cortisol secreted; if brain is at fault, CRH levels high; if pituitary at fault, CRH levels low. Hypertension from excess aldosterone and masculinzation from excess adrenal DEA are also consequences. Cushing’s Syndrome (hyperadrenalism from any other cause): -Ectopic ACTH secretion from tumor – cortisone levels very high because no negative feedback; hypertension from excess aldosterone - CRH levels would be very low - Primary hyperadrenalism – CRH and ACTH levels low -Iatrogenic – methyl prednisone or cortisone therapy for inflammatory disease results in Cushingoid symptoms but with low ACTH values – adrenal cortex shrinks; hypotension from aldosterone deficit is one consequence.