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]Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006 Aug;65(2):265-73.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2265.2006.02562.x
http://www.ncbi.nlm.nih.gov/pubmed/16886971?tool=bestpractice.com
[2]Serri O, Chik CL, Ur E, et al. Diagnosis and management of hyperprolactinemia. CMAJ. 2003 Sep 16;169(6):575-81.
http://www.cmaj.ca/content/169/6/575.long
http://www.ncbi.nlm.nih.gov/pubmed/12975226?tool=bestpractice.com
[3]Mah PM, Webster J. Hyperprolactinemia: etiology, diagnosis, and management. Semin Reprod Med. 2002 Nov;20(4):365-74.
http://www.ncbi.nlm.nih.gov/pubmed/12536359?tool=bestpractice.com
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]Serri O, Chik CL, Ur E, et al. Diagnosis and management of hyperprolactinemia. CMAJ. 2003 Sep 16;169(6):575-81.
http://www.cmaj.ca/content/169/6/575.long
http://www.ncbi.nlm.nih.gov/pubmed/12975226?tool=bestpractice.com
[3]Mah PM, Webster J. Hyperprolactinemia: etiology, diagnosis, and management. Semin Reprod Med. 2002 Nov;20(4):365-74.
http://www.ncbi.nlm.nih.gov/pubmed/12536359?tool=bestpractice.com
[4]Josimovich JB, Lavenhar MA, Devanesan MM, et al. Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication. Fertil Steril. 1987 May;47(5):785-91.
http://www.ncbi.nlm.nih.gov/pubmed/3569555?tool=bestpractice.com
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]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
[6]Gibney J, Smith TP, McKenna TJ. Clinical relevance of macroprolactin. Clin Endocrinol (Oxf). 2005 Jun;62(6):633-43.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2265.2005.02243.x
http://www.ncbi.nlm.nih.gov/pubmed/15943822?tool=bestpractice.com
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]Bole-Feysot C, Goffin V, Edery M, et al. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998 Jun;19(3):225-68.
https://academic.oup.com/edrv/article/19/3/225/2530791
http://www.ncbi.nlm.nih.gov/pubmed/9626554?tool=bestpractice.com
Although it derives from an ancestral hormone common to growth hormone and human placental lactogen, PRL displays little structural homology with these hormones.[5]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
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]Bole-Feysot C, Goffin V, Edery M, et al. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998 Jun;19(3):225-68.
https://academic.oup.com/edrv/article/19/3/225/2530791
http://www.ncbi.nlm.nih.gov/pubmed/9626554?tool=bestpractice.com
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]Arowojolu AO, Akinloye O, Shittu OB. Serum and seminal plasma prolactin levels in male attenders of an infertility clinic in Ibadan. J Obstet Gynaecol. 2004 Apr;24(3):306-9.
http://www.ncbi.nlm.nih.gov/pubmed/15203635?tool=bestpractice.com
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]Kanyicska B, Lerant A, Freeman ME. Endothelin is an autocrine regulator of prolactin secretion. Endocrinology. 1998 Dec;139(12):5164-73.
https://academic.oup.com/endo/article/139/12/5164/2991322
http://www.ncbi.nlm.nih.gov/pubmed/9832457?tool=bestpractice.com
[10]Sarkar DK, Kim KH, Minami S. Transforming growth factor-beta 1 messenger RNA and protein expression in the pituitary gland: its action on prolactin secretion and lactotropic growth. Mol Endocrinol. 1992 Nov;6(11):1825-33.
http://www.ncbi.nlm.nih.gov/pubmed/1480172?tool=bestpractice.com
[11]Shah GV, Pedchenko V, Stanley S, et al. Calcitonin is a physiological inhibitor of prolactin secretion in ovariectomized female rats. Endocrinology. 1996 May;137(5):1814-22.
http://www.ncbi.nlm.nih.gov/pubmed/8612519?tool=bestpractice.com
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]Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008 Feb;29(1):1-41.
https://academic.oup.com/edrv/article/29/1/1/2354965
http://www.ncbi.nlm.nih.gov/pubmed/18057139?tool=bestpractice.com
