Poster Presentation The International Congress of Neuroendocrinology 2014

Estrogen receptor-α and progestin receptor modulate the effect of kisspeptin on TIDA neurons and prolactin secretion (#247)

Nayara S. S. Aquino 1 , Patricia C. Henriques 1 , Roberta Araujo-Lopes 1 , Izadora A. R. Batista 1 , Celso R. Franci 2 , Adelina M. Reis 1 , Raphael E. Szawka 1
  1. Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  2. Fisiologia, Universidade de São Paulo, Ribeirão Preto, Brazil

We have shown that kisspeptin stimulates prolactin (PRL) release through inhibition of tuberoinfundibular dopaminergic (TIDA) neurons in an estradiol (E2)-dependent manner. We investigated here the role of estrogen (ER) and progestin (PR) receptors in kisspeptin regulation of PRL secretion in female rats. Ovariectomized (OVX) rats receiving different hormonal treatments were injected with i.c.v. kisspeptin-10 (Kp-10; 3 nmol) or vehicle (n = 5–7 per group). Plasma PRL levels were measured in blood samples taken from a jugular-vein catheter or from trunk blood in rats decapitated 10 minutes after i.c.v. injections. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were determined in the median eminence (ME). Tamoxifen, a selective ER modulator, was used to suppress ER activation. In a preliminary experiment, tamoxifen blocked the PRL surge in OVX, E2-treated rats (OVX+E2), and only slightly increased PRL levels in OVX rats. Kp-10 increased PRL and decreased DOPAC levels in the ME of OVX+E2 rats (P<0.05) and these effects were prevented in OVX+E2 rats pretreated with tamoxifen. Propylpyrazole triol (PPT) and diarylpropionitrile (DPN) were employed as selective agonists of ERα and ERβ, respectively. PPT-treated OVX rats displayed decreased ME DOPAC and increased PRL release induced by Kp-10 (P<0.05), whereas Kp-10 had no effect in oil- or DPN-treated OVX rats. To evaluate the role of PR, OVX rats were treated with E2 and progesterone (OVX+E2P). PRL response to Kp-10 was greater in OVX+E2P than in OVX+E2 rats, which was associated with a reduction in both dopamine and DOPAC levels in the ME (P<0.05). These responses were prevented in OVX+E2P rats treated with the PR antagonist RU-486. Thus, the facilitatory effect of E2 on kisspeptin regulation of TIDA neurons and PRL secretion depends on ERα but not ERβ. Moreover, progesterone potentiates the effect of kisspeptin on TIDA neurons via PR activation.
Financial support: FAPEMIG, CNPQ, PRPq-UFMG, FAPESP.