Hyperprolactinemia is a condition of elevated serum prolactin (PRL). Normal PRL levels in women and men are <25 micrograms/L (500 milliunits/L) and 20 micrograms/L (400 milliunits/L), respectively.[1] [2] [3]
Epidemiology
Hyperprolactinemia is the most common endocrine disorder of the hypothalamus-pituitary axis. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to 5% in a family planning clinic. It increases to 9% in women with amenorrhea and occurs in 25% of those with galactorrhea. Among women presenting with concomitant amenorrhea and galactorrhea, 70% are hyperprolactinemic. The condition also accounts for 5% of men who present with impotence or infertility.[2] [3] [4] Although uncommon, hyperprolactinemia can also present in children.
Pathophysiology
The hormone PRL is a 199-amino acid peptide synthesized and secreted by lactotroph cells in the anterior pituitary gland; 80% of circulating PRL exists as a 23 kilodalton (kD) monomer. Dimeric PRL (also known as big PRL) has a molecular weight of 50 kD to 60 kD and accounts for 10% to 15%; the remainder is macroprolactin (also known as big-big PRL), a high molecular weight (>150 kD) complex of monomeric PRL and IgG.[5] [6] PRL is also produced by numerous extrapituitary tissues, including various brain regions, lymphocytes, mammary epithelial cells, and tumors, as well as the decidua, myometrium, lacrimal gland, thymus, and spleen.[7] Although it derives from an ancestral hormone common to growth hormone and human placental lactogen, PRL displays little structural homology with these hormones.[5]
The main action of PRL is to stimulate breast epithelial cell proliferation and induce milk production. In addition to its lactogenic role, PRL promotes the formation and action of the corpus luteum and suppresses the pulsatile secretion of gonadotropin-releasing hormone (GnRH). Suppression of GnRH by prolactin results in decreased levels of follicle-stimulating hormone and luteinizing hormone.[7] Moreover, prolactin plays a direct inhibitory role in spermatogenesis and steroidogenesis, as its receptors have been detected in Sertoli and Leydig cells in the testes.[8]
PRL secretion is pulsatile and controlled predominantly by the inhibitory effect of dopamine released from the hypothalamus. Dopamine acts through its D2 receptors on lactotroph cells. Other inhibitory factors are endothelin peptides, tumor growth factor-beta 1, and calcitonin.[9] [10] [11] Estrogens stimulate the proliferation of lactotroph cells, resulting in an increased quantity of these cells in premenopausal women, especially during pregnancy. PRL production is also stimulated by thyrotropin-releasing hormone, vasoactive intestinal peptide, and oxytocin.[5]
