Prolactin gene expression in the pituitary of rats subjected to vaginocervical stimulation requires Erk-1/2 signaling.

Vaginocervical stimulation (VCS) induces twice-daily prolactin (PRL) surges resulting in pseudopregnancy in the rat. Furthermore, activation of the extracellular signal-regulated kinase-1/2 (Erk-1/2) is involved in the effect of estradiol (E2) on the Prl gene expression in pituitary cells. Herein, we investigated whether Erk-1/2 signaling is involved in the control of Prl expression in the pituitary of VCS rats and whether VCS regulates the effect of E2 on Erk-1/2 and Prl in the pituitary. Estrous rats were assigned as control or VCS groups and 0, 6, 12 or 24h later the levels and localization of phosphorylated Erk-1/2 (p-Erk-1/2) were analyzed in the pituitary. The effect of an Erk-1/2 inhibitor PD98059 on the Prl level in the pituitary of control or VCS rats was also analyzed. Other control or VCS rats were treated with E2 and the level of p-Erk-1/2 and Prl were measured in the pituitary. In control rats, p-Erk-1/2 decreased at 6 and 12h and increased at 24h while Erk-1/2 was phosphorylated at all time points in VCS rats. p-Erk-1/2 was localized only in the anterior pituitary. PD98059 decreased Prl level in VCS, but not in control rats. Estradiol decreased Erk-1/2 phosphorylation although did not change Prl level in the pituitary of control or VCS rats. These findings show that prolonged activation of Erk-1/2 is necessary to induce Prl expression in the pituitary of VCS rats; however, VCS does not influence the role of E2 on the activation of Erk-1/2 and Prl expression the pituitary.

17beta-oestradiol and progesterone regulate anandamide synthesis in the rat uterus.

Anandamide is an endocannabinoid known to participate in reproductive processes. This study observed that 17beta-oestradiol and progesterone modulated the production of anandamide and its metabolizing enzymes in the rat uterus. Anandamide production was highest at the oestrous stage and 17beta-oestradiol and progesterone stimulated its synthesis in ovariectomized rats. During early pregnancy, anandamide production remained constant on days 1-5 of gestation and diminished towards day 6. On day 6, implantation sites showed lower synthesis compared with interimplantation sites. In the delayed implantation model, 17beta-oestradiol inhibited anandamide synthesis compared with progesterone. During pseudopregnancy, anandamide production did not decrease towards day 6 as occurred during normal gestation. The administration of 17beta-oestradiol augmented anandamide production in rats on day 5 of pseudopregnancy; the treatment with mifepristone did not produce any change in anandamide synthesis. Anandamide-metabolizing enzymes were regulated by progesterone and 17beta-oestradiol. The effect of ovarian hormones on the synthesis of anandamide depends on different physiological conditions, oestrous cycle and early pregnancy, and on the presence of the activated blastocyst. Thus, ovarian hormones, as signals that emanate from the mother, operate in conjunction with the blastocyst intrinsic programme, regulating the synthesis of anandamide in a specific manner during crucial reproductive events that may compromise pregnancy outcome.