Kisspeptin reverses hyperprolactinemia-induced ovarian acyclicity

By medwireNews Reporters

Kisspeptin neurons appear to play a role in hypogonadotropic anovulation caused by excessive levels of prolactin, research shows.

In a mouse model, the administration of kisspeptin restored gonadotropin secretion and ovarian cyclicity, which raises the possibility that kisspeptin might "serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women," say researchers.

Published in the Journal of Clinical Investigation, senior investigator Nadine Binart (Université Paris-Sud, France) and colleagues report that hyperprolactinemia has been previously proposed to block ovulation by inhibiting the release of gonadotropin-releasing hormone (GnRH).

To date, however, the cause of the gonadotropic deficiency, hypothesized to result from the direct suppression of prolactin through the inhibition of GnRH, has never been proven.

In previous studies, kisspeptin neurons, which express prolactin receptors, were identified as regulators of GnRH neurons. Kisspeptin is encoded by the Kiss1 gene and is critically important for pubertal maturation and regulation of reproductive function.

In order to mimic the pathology of anovulation, Binart and colleagues infused female mice with prolactin.

The mouse model showed that the increased levels of prolactin induced anovulation, reduced levels of GnRH and gonadotropic secretion, and reduced the expression of kisspeptin.

The mice were then given daily injections of kisspeptin starting on day 8 of prolactin treatment and continued to day 28. The administration of kisspeptin restored gonadotropin secretion and estrous cyclicity.

In an editorial accompanying the study, Ursula Kaiser (Brigham and Women's Hospital, Boston, Massachusetts, USA) said the study "provides important insights into the neural pathways by which the hypothalamic-pituitary-gonadal axis is suppressed to cause infertility."

She notes that the ability of exogenously administered kisspeptin to reverse the hypogonadotropic effects of hyperprolactinemia has potential therapeutic implications, especially since some women are resistant or intolerant to dopamine agonists.

"In this regard, it is striking that a single daily dose of kisspeptin was sufficient to restore ovulatory cycles in the mouse model," writes Kaiser.

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