Prolactin is a polypeptide hormone, named from its well- known effects to promote lactation. It is essential for successful reproduction in man and mammals, although it is known to have a wide variety of non- reproductive effects whose clinical significance remains uncertain. Prolactin is secreted by lactotrophic cells of anterior pituitary gland, but many other sites of production have been identified, including the endometrium, immune cells including T- lymphocytes, and skin. Circulating prolactin is generally assumed to derive mainly from pituitary secretion, and extrapituitary production is thought to exert mainly local paracrine effects within tissues. The clinical condition of hyperprolactinaemia is almost always attributable to abnormal pituitary prolactin secretion and ectopic neoplastic causes of hyperprolactinaemia are extremely rare.
Lactotrophic cells constitute a large proportion (25– 40%) of the endocrine cell types in the pituitary, though their numbers and size can vary during and after pregnancy. This indicates a significant degree of plasticity in pituitary structure that may be important in the susceptibility of the pituitary to the frequent formation of microadenomas.
Unlike other pituitary hormones, pituitary prolactin secretion is under predominantly inhibitory control from the hypothalamus, and transection of the pituitary stalk results in sustained hyperprolactinaemia. The prolactin inhibitory factor was identified as dopamine, secreted by tubero- infundibular neurons, which acts on D2 receptors on lactotrophic cells to reduce prolactin synthesis and secretion. A series of other hypothalamic hormones may act as stimuli to prolactin secretion, including TRH, VIP, galanin, and fibroblast growth factor. However the main physiological mechanism for pulses of prolactin secretion is thought to be the episodic interruption of dopamine inhibition.
The reproductive effects of prolactin are found at all levels of the hypothalamo- pituitary- gonadal axis, with effects on the frequency of gonadotropin- releasing hormone (GnRH) pulses, inhibition of the secretion of gonadotrophins, and suppression of luteolysis. These multiple levels of suppression of gonadal function mean that the hyperprolactinaemia that normally occurs during breastfeeding effectively suppresses fertility.
A variety of non- reproductive effects of prolactin have been documented which are of less clear significance in man. The prolactin receptor (PRLR) is found in many peripheral tissues, and studies of prolactin and PRLR knockout mice have clearly confirmed not only the reproductive effects of prolactin, but also effects on maternal behaviour, adipose tissue depots, bone mineralization, and immune response.
