Genital Sensory Stimulation Shifts Estradiol Intraoviductal Signaling from Nongenomic to Genomic Pathways, Independently from Prolactin Surges

Estradiol (E2) accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS) to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL) surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2) or pregnancy (P2). Activated ST AT 5a/b (phosphorylated) was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating.

Increased sensitivity and accumulation os estradiol in the rat oviduct during early pregnancy

We have previously reported that a single injection of estradiol-17 beta (E2) given on day 3 of pregnancy (P3) is far more effective for accelerating oviductal transport in the rat, than treatment given on day 1 (P1). In order to quantify this change, dose-response curves were established for six different doses of E2 (range 0.031 to 1.00 micrograms per animal) given on P1, P2 or P3. In addition, a possible mechanism was explored by comparing the plasmatic and oviductal levelsof E2 between 30 and 180 min following treatment with E2 on P1 or P3. As the interval from ovulation to treatment was increased, the transport of a larger number of embryos was accelerated and a smaller dose was required. The minimal effective dose decreased 30-fold from P1 to P3, the oviducts accumulated 20 percent to 90 percent more E2 on P3 than on P1, tissuelevels were 6- to 48-fold higher than plasma levels and the latter did not differ between P1 and P3. It is concluded that the oviduct exhibits increased sensitivity and responsiveness to E2 on P3 and this isassociated with greater accumulation of the hormone in the organ, not attributable to higher E2 plasma levels