Poster Presentation The International Congress of Neuroendocrinology 2014

Effects of tamoxifen on estrogen regulation of luteinizing hormone and prolactin secretion in female rats (#341)

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

Tamoxifen is widely known as a selective estrogen receptor modulator but its effects on luteinizing hormone (LH) and prolactin (PRL) secretion remain elusive. We investigated here the effects of tamoxifen on estradiol regulation of LH and PRL release in female rats. Ovariectomized (OVX) rats were treated for 3 days with oil (OVX; n=5), estradiol (OVX+E;n=6), tamoxifen (OVX+T; n=4), or estradiol and tamoxifen (OVX+ET; n=6). On the fourth day, blood samples were taken hourly from a jugular-vein catheter from 13:00 to 18:00 h. Rats were perfused and the brains processed for immunohistochemical analysis. OVX+E rats had low LH levels at 13:00–15:00 h and displayed a LH surge between 16:00–18:00 h (P<0.01), reflecting negative and positive-feedback effects of estradiol, respectively. OVX+T rats showed plasma LH similar to OVX+E and lower than OVX rats (P<0.05) and the estradiol-induced LH surge was blocked in OVX+ET rats (P<0.05). The number of kisspeptin-immunoreactive neurons in the arcuate nucleus (ARC) was 50% lower in OVX+E compared with OVX rats (P<0.001). This inhibitory effect of estradiol was partially prevented in OVX+ET rats (P<0.05), whereas tamoxifen alone had no effect on ARC kisspeptin. OVX+E2 rats showed a marked increase in c-Fos expression in the anteroventral periventricular nucleus (AVPV), and this positive-feedback effect of estradiol was completely blocked in OVX+ET rats(P<0.05). Plasma PRL was equally low in OVX and OVX+T rats. OVX+E2 rats exhibited a PRL surge between 15:00–18:00 h, which was totally suppressed in OVX+ET rats (P<0.001). In conclusion, tamoxifen effectively blocks the positive-feedback of estradiol on AVPV neurons and LH secretion as well as the estradiol-induced PRL surge. On the other hand, tamoxifen only partially interferes in the estradiol inhibition of ARC kisspeptin neurons and seems to exert a negative-feedback effect on LH secretion.

Financial Support: FAPEMIG, CNPq, PRPq-UFMG, FAPESP.