The clinical relevance of chronic high prolactin levels is not yet fully understood. Although one biological function of prolactin is to stimulate mammary tissue to produce milk, over 300 other biological activities for prolactin have been identified (Goffin et al. 2002). Prolactin is involved in the regulation of reproductive function, for example, by inhibiting production of estrogen and testosterone by other tissues. Prolactin is also involved in various homeostatic processes, including enhancement of immune system function (Neidhart 1998; Yu-Lee 2002), regulating angiogenesis (Corbacho et al. 2002), and osmoregulation (Shennan 1994).
Further research will likely reveal other roles for prolactin, because pro-lactin is produced by multiple tissues and interacts with multiple other neurotransmitter, peptide, and hormonal systems. In addition to the anterior pituitary gland, numerous other brain areas produce prolactin, as do breast tissue, placenta, uterus, prostate, and lymphocytes (Bole-Feysot et al. 1998; Goffin et al. 2002). Other peptides are known to be affected by or to affect prolactin levels; examples include estrogen, testosterone, lep-tin, galanin, somatostatin, calcitonin, bombesin-like peptides, neurotensin, endothelins, neuropeptide Y, and cholecystokinin. In addition, neu-rotransmitter systems other than dopamine are affected by and/or affect prolactin, including glutamate, aspartate, glycine, gamma-aminobutyric acid (GABA), and nitric oxide. Although prolactin's role in reproductive function is relatively well understood, prolactin's other homeostatic functions are less understood; nevertheless, the importance of prolactin is suggested by its widespread distribution and interaction with multiple other systems.
In addition to pregnancy and lactation, many other factors affect serum prolactin levels. A circadian variation exists in which levels increase substantially after the noontime meal, making fasting determinations more re liable than those obtained later in the day. In women, prolactin levels vary with time of menstrual cycle, with the peak at day 12 of the cycle and the nadir during the follicular phase. In addition, the number of live births plays a role in premenopausal women, with prolactin levels varying inversely with parity. In premenopausal women, high intake of saturated fats is associated with elevated prolactin levels (Wang et al. 1992; Wennbo and Tornell 2000). Primary hypothyroidism can also cause hyperprolactine-mia, but values seldom exceed 50 ng/mL. The upper limit of normal prolactin levels is 23-25 ng/mL in women (obtained at day 3 of the cycle in premenopausal women) and 20 ng/mL in men.
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