Progesterone augments copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from explants of the median eminence of immature female rats: an estrogen-dependent process.
We have previously shown that extracellular copper (Cu) amplifies prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA) of adult male rats, and that amplification is a post-PGE2 receptor event involving the adenylate cyclase system. We addressed the question: Is the process of Cu-amplified PGE2 stimulation of LHRH release regulated by ovarian steroids and, if so, is the regulatory steroid estrogen and/or progesterone? Immature female rats (30-32 days old) were ovariectomized and 6 days later treated with a combination of these steroids: E, sc implant of 17 beta-estradiol in a Silastic capsule for 3 days; EEi, E plus im injection of 17 beta-estradiol (2 micrograms/rat) 24 h before killing; and P, either im injection of 0.08 mg/kg progesterone 1 h before killing or 10(-9) M P included in the incubation buffer starting 1 h before Cu/PGE2 exposure. Controls were treated with the vehicle. MEAs were incubated for 5 min with 150 microM Cu, for 15 min with 10 microM PGE2, and then for 45 min with buffer (Cu/PGE2); LHRH release into the medium was measured by RIA. Cu/PGE2-stimulated LHRH release from MEA of intact rats was about 10 times greater than basal release. Ovariectomy led to a 50% reduction in Cu/PGE2-stimulated release [sham, 20.6 +/- 2.0 (mean +/- SE); ovariectomized, 9.4 +/- 1.8], pg/30 mm/MEA; and neither E, EEi, nor P significantly altered this response. In contrast, administration of P to either E- or EEi-primed rats augmented Cu/PGE2 stimulation of LHRH release 3.5-fold (E vs. EP or EEi vs. EEiP); however, P did not augment stimulation of LHRH release by Cu alone or PGE2 alone. Also, inclusion of P in the incubation buffer was as effective as in vivo P in augmenting Cu/PGE2 stimulation of LHRH release from the MEA of EEi-primed rats. On the other hand, in vitro P by itself did not alter LHRH release. These effects of P on the response of the MEA to Cu/PGE2 were not accompanied by a significant increase in the MEA content of LHRH. The process of Cu/PGE2 stimulation of LHRH release is regulated by ovarian steroids, so that ovariectomy leads to a marked reduction of the response of the MEA to Cu/PGE2, and P augments this response in an estrogen-dependent manner. Moreover, it is the secretory process elicited by the combined effects of Cu and PGE2 that is augmented by P.(ABSTRACT TRUNCATED AT 400 WORDS)
Bhasker
K R
KR
Department of Obstetrics and Gynecology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235.
Barnea
A
A
D000818:Animals; D003300:Copper / Q000494:pharmacology*; D015232:Dinoprostone; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007700:Kinetics; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D012741:Sexual Maturation; D012826:Silicone Elastomers
D011458:Prostaglandins E; D012826:Silicone Elastomers; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D003300:Copper; D015232:Dinoprostone