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New insights into human prolactin pathophysiology

genomics and beyond

Chang, Sydneya,b; Copperman, Alan B.a,b

Current Opinion in Obstetrics and Gynecology: August 2019 - Volume 31 - Issue 4 - p 207–211
doi: 10.1097/GCO.0000000000000545

Purpose of review To briefly summarize what is known regarding hyperprolactinemia and prolactin-secreting tumors, and review recent findings.

Recent findings Prolactin was previously thought to inhibit secretion of gonadotropin-releasing hormone (GnRH) by directly inhibiting the firing of GnRH neurons, resulting in hypogonadotropic hypogonadism and infertility. However, kisspeptin has recently been implicated as the mediator of hyperprolactinemia-induced infertility, by acting upstream of the GnRH neurons as an integrator of endocrine signals.

Macroprolactin is generally considered to be inactive and clinically insignificant, but new studies have suggested that patients with macroprolactinemia may have reproductive manifestations as well as sexual dysfunction.

Several mutations and polymorphisms in the prolactin receptor have been described, which could describe a genetic cause for prolactinomas and characterize cases of isolated familial hyperprolactinemia.

Kisspeptin and tyrosine kinase inhibitors have emerged as potential new therapeutic targets for the treatment of hyperprolactinemia and dopamine-resistant prolactinomas.

Summary Molecular studies are shedding light on the pathophysiology of hyperprolactinemia and the effects of excess prolactin production on the reproductive system. Similarly, genetic studies have begun to reveal how differences in prolactin receptor function may account for some of the previously ‘idiopathic’ cases of hyperprolactinemia and bring to light new causes of prolactinomas. Further elucidation of the transcriptional pathways affected by these genetic changes may help to create new therapeutic targets.

aDepartment of OBGYN and Reproductive Science, Icahn School of Medicine at Mount Sinai, Klingenstein Pavilion, New York City

bReproductive Medicine Associates of New York, New York, USA

Correspondence to Alan B. Copperman, MD, Reproductive Medicine Associates of New York, 635 Madison Avenue, 10th Floor, New York, NY 10022, USA. Tel: +1 212 756 5777; e-mail:

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