Increased estradial Prolactin is a polypeptide produced by the lactotrophs of the pituitary. It is responsible .for the initiation and maintenance of lactation. As with several pituitary hormones, prolactin is secreted in a circadian, fashion with the highest levels being attained during sleep and a nadir occurring between 10 am and noon. Prolactin is secreted in a pulsatile .fashion, the amplitude and frequency of which not only varies throughout the day but is also impacted upon by a variety of physiology stimuli i.e., suckling, stress and increased level of ovarian steroids primarily estrogens. "The general view is that lactotrophs have spontaneously high secretary activity". Therefore pituitary prolactin secretion is under a tonic and predominantly inhibitory control exeed by the hypothalamus. - Hypothalmus releases prolactin inhibitory factor (PIF) which inhibits prolactin release. - PIE is actually dopamine and it suppresses prolactin synthesis and secretion by means of D2 receptors. - These actions constitute the physiologic basis of therapeutic effect of dopamine agonists in hyperprolactinemia. Prolactin acts on the breast tissue where in the setting of estrogen priming, it stimulates lactation. Effect of physiological hormones on prolactin secretion Glucocoicoids seem to have an inhibitory role on PRL secretion. - These hormones stimulate the differentiation of somatotrophs but suppress that of lactotrophs. - Long-term elevation of the serum glucocoicoid levels by chronic administration of coicotrophin (ACTH) or hydrocoisone or by prolonged stress decreases PRL secretion. Estrogens and thyroid hormones have opposite effects on PRL synthesis and release. - "Estrogen increases prolactin levelQ by acting at both pituitary and hypothalamic level" - At pituitary level it increases prolactin secretion by controlling PRL gene expression and modifying its sensitivity to physiological stimuli. - At hypothalamic level it inhibits the activity of all three types of hypothalamic neuroendocrine dopaminergic neurone. - Low thyroxine (T4) and triiodothyronine (T3) levels increase TRH-induced PRL secretion, whereas high T4 and T3 levels inhibit PRL mRNA accumulation and release. An impoant point Increased estrogen causes hyperprolactinemia But Hyperprolactinemia causes decrease in estrogen Prolactin also acts at the hypothalamus to inhibit the secretion of gonadotropin releasing hormone (GnRH). - Inhibition of GnRH results in a decrease in the release of LH and FSH from the anterior pituitary. In females - This leads to decreased in estrogen and progesterone synthesis and secretion by the ovaries and a failure of ovarian .follicular maturation. In males - This leads to decrease in testicular production and synthesis of testosterone and a halt in spermatogenesis. Causes of hyperp rolactinemia Hypothalamic diseases Heavy metals and other chemical substances * Tumors (craniopharyngioma, meningioma, dysgerminoma, third * Manganese * Organic mercury ventricle tumor, cyst, glioma, harnaoma, and metastasis), * Lead * Cadmium * Infiltrative disease (sarcoidosis, tuberculosis, Langerhans's cell * Uranium * Arsenic histiocytosis, and eosinophilic granuloma). * Bari um * Cranial irradiation * Vascular abnormalities * Pseudotumor cerchri * Genetic syndromes (multiple endocrine neoplusia syndrome Carney complex, McCune-Albright syndrome). Pituitary diseases Neurogeic * Functioning and nonfunctioning * Chest wall lesions adenomas, MEN I * Spinal cord lesions * Empty sella sendrome * Breast stimulation * Lymphocytic hypophysitis * Physical or psycho? Primitive tumors (meningioma, germinoma, metastasis, and lymphoma) and metastasis infiltrative diseases (giant cell granuloma and sarcoidosis) logic stress Drugs Other * Neurolepticsdeg (phenothiazines, butyrophenones, and atypical * Hypothyroidism * Chronic renal failure antipsychotics). * Cirrhosis * Antidepressantsdeg (tricyclic and * Adrenal insufficiency tetracyclic antidepressants, MAO inhibitors, SSEIs and others). * Pseudocyesis * Antihypeensive medications (verapamil methyldopa, and reserpine). Gastrointestinal medications (metoclopramide, domperodone and H2 blockers). * Opiates, Cocaine, Estrogensdeg, Protease inhibitors