α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats

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Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner.We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion.Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments.Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen.Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)a, propylpyrazole triol, but not of ERb, diarylpropionitrile.Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser 40 -phosphorylated TH in the ME.Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486.We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay.Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats.Thus, we provide evidence that Kp stimulation of PRL release requires ERa and is potentiated by progesterone via PR activation.Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge.(Endocrinology 158: 1812-1826, 2017) P rolactin (PRL) is a pituitary hormone recognized mainly for its critical role in promoting lactation (1).However, a wide range of reproductive and nonreproductive functions are also attributed to PRL.In rodents, for example, PRL acts as a luteotrophic hormone, essential for proper luteal function and fertility (2), besides stimulating parental behavior (3).On the other hand, chronic hyperprolactinemia is a frequent cause of infertility in humans