Week 5

Small outgrowth of the forebrain Size of half a pea Two functional parts  Adenohypophysis (anterior pituitary)  Neurohypophysis (posterior pituitary)

Hypothalamus • Hypothalamic neurons release hormones directly into capillary plexus Anterior pituitary • Blood supply from median eminence of hypothalamus – portal system • Hormones from hypothalamus to pituitary • Sympathetic/parasympathetic nerves Posterior pituitary • Supraoptic and paraventricular nuclei in hypothalamus

CRH: Corticotrophin releasing hormone (ACTH) TRH: Thyrotropin releasing hormone GHRH: GH releasing hormone Somatostatin: GH inhibition GnRH: Gonadotrophin (LH, FSH) releasing hormone Dopamine: Prolactin inhibition Vasopressin: ACTH release

The anterior pituitary produces six major hormones:  (1) prolactin (PRL)  (2) growth hormone (GH)  (3) adrenocorticotropic hormone (ACTH)  (4) luteinizing hormone (LH)  (5) follicle-stimulating hormone (FSH)  (6) thyroid-stimulating hormone (TSH)

Can malfunction in several ways, usually as a result of developing a noncancerous tumour (adenoma) Prolactin-secreting adenomas are divided into 2 groups:  Microadenomas (more common in premenopausal women), which are smaller than 10 mm)  Macroadenomas (more common in men and postmenopausal women), which are 10 mm or larger.

Disorders that result from overproduction of pituitary hormones include  Acromegaly or gigantism: Growth hormone  Cushing disease: Adrenocorticotropic hormone ( ACTH),  Galactorrhea (the secretion of breast milk by men or by women when not pregnant): Prolactin  Erectile dysfunction: Prolactin  Infertility (particularly in women): Prolactin Disorders that result from underproduction of pituitary hormones include  Central diabetes insipidus: Vasopressin  Hypopituitarism: Multiple hormones

Prolactin secretion is controlled primarily by inhibition from the hypothalamus and it is not subject to negative feedback directly or indirectly by peripheral hormones.

Dopamine serves as the major prolactin- inhibiting factor or brake on prolactin secretion.  Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors on lactotrophs, and inhibits both the synthesis and secretion of prolactin.  In addition to tonic inhibition by dopamine, prolactin secretion is positively regulated by several hormones, including thyroid-releasing hormone, gonadotropin-releasing hormone and vasoactive intestinal polypeptide.

Excess prolactin, or hyperprolactinemia, can lower levels of sex hormones in both women and men. Related complications can include  infertility  bone loss (osteoporosis)

High blood prolactin concentration interferes with the function of the testicles, the production of testosterone (the main male sex hormone), and sperm production

Prolactin inhibits pulsatile GnRH secretion and consequently inhibits the pulsatile release of FSH, LH and testosterone.  This results in marked effects on spermatogenesis ranging from alteration in sperm quality to complete spermatogenic arrest.  As a result, the patient may present with secondary hypogonadism or male infertility. Furthermore, prolactin may also impact male fertility through a direct effect on spermatogenesis.

Defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications Imbalance between estrogen action relative to androgen action at the breast tissue level appears to be the main etiology of gynecomastia

(high prolactin) This usually manifests with oligomenorrhoea or amenorrhoea, and diagnosis in such cases is straightforward. Another common symptom is “galactorrhoea”, which is the occurrence of a milky discharge from the breast in a woman who has not recently been pregnant. The discharge is the result of persistent high PRL levels stimulating the mammary gland for milk production.

Is the apparent increase in serum prolactin without symptoms Serum prolactin molecules can polymerize and subsequently bind to immunoglobulin G (IgG).  This form of prolactin is unable to bind to prolactin receptors and exhibits no systemic response.  In the asymptomatic patient with hyperprolactinemia, this condition should be considered.

Vision problems, caused when the tumour presses on the optic nerves or optic chiasm, the part of the brain where the two optic nerves cross over each other headaches low levels of other pituitary hormones, such as thyroid hormones and cortisol

Promotes growth: skeleton, muscles, viscera Effects mediated by somatomedins Released at night during growth Variety of metabolic effects  Anabolic, positive nitrogen balance  Anti-insulin

Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration. Ghrelin is a peptide hormone secreted from the stomach. Ghrelin binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.

Increase rate of protein synthesis in most of cells Increase mobilization of fatty acids for energy production Decrease rate of glucose utilization throughout body

One of several growth factors necessary for normal human development. IGF-1 is synthesized mainly by the liver but also locally in many tissues.  Activation of the growth hormone receptor stimulates the synthesis and secretion of insulin-like growth factor-1 (IGF- 1), a small peptide (about 7.5 kD) structurally related to proinsulin.  IGF-1 circulates in the blood at high concentrations and acts as a mitogen, stimulating DNA, RNA and protein synthesis.

 Giantism is the result of excessive growth hormone secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a tumour of somatotrophs.  Acromegaly results from excessive secretion of growth hormone in adults, usually the result of benign pituitary tumours. The onset of this disorder is typically insidious, occurring over several years.  Growth hormone deficiency

Is a disorder of disproportionate skeletal, tissue, and organ growth.  Characterized by hypersecretion of growth hormone (GH),which is caused by the existence of a secreting pituitary tumour in more than 95% of acromegaly cases.  In rare instances, elevated GH levels are caused by extra pituitary disorders.  Hypersecretion of GH in turn causes subsequent hepatic stimulation of insulin-like growth factor-1 (IGF-1) leading to enlarge physical features.  Peripheral neuropathies occur commonly because of compression of nerves by adjacent fibrous tissue and endoneural fibrous proliferation.

Like Acromegaly however occurs in adulthood

GH excess affects insulin sensitivity and gluconeogenesis and can alter pancreatic β-cell function, leading to a derangement of glucose metabolism in a considerable percentage of acromegaly patients.  Induces hyperglycaemia by increasing endogenous glucose production and decreasing peripheral glucose disposal in muscle.

Functional tests for GH 1. Basal plasma GH level: High 2. Plasma Prolactin level: High 3. Glucose tolerance suppression test: 75 grams of glucose to be given orally, GH and blood glucose level to be measured 2 hourly  Normal: Suppression of GH by hyperglycaemia 1. Acromegaly or gigantism: No suppression 2. Visual field defects: Due to pressure by pituitary adenoma 3. CT scan skull