Abstract:
Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading
causes of infertility in women aged 25–34. Hyperprolactinemia has been proposed to block ovulation through
inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as
major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused
female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation,
reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration
restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major
role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as
an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or
intolerant to dopamine agonists.
