title: Suppression of luteal estradiol receptors and progesterone synthesis by a gonadotropin-releasing hormone agonist (WY-40972) during midgestation.
abstract: Our recent studies demonstrated that the continuous administration of a gonadotropin-releasing hormone agonist (GnRH-Ag: WY-40972) in early pregnancy or midpregnancy induces abortion in rats by suppressing the plasma levels of progesterone (P) within 24 h. This fall in P levels is not accompanied by a fall in ovarian vein plasma testosterone (T) or estradiol (E). To determine whether the suppression of P by GnRH-Ag at midpregnancy is due to decreased E present in the corpora lutea (CL) and/or a decrease in luteal receptors of E, rats were treated continuously on Days 11-14 of pregnancy with 5 micrograms/day of GnRH-Ag delivered by an osmotic minipump. Ovarian blood samples were obtained on Day 12; at autopsy, CL were harvested and incubated with Medium 199 for 4 h at 37 degrees C under an atmosphere of 95% O2:5% CO2. Additional rats were killed on Day 12 or 14; CL were isolated from the ovary and pooled within the group for measurement of nuclear and cytosolic E receptors. While the net synthesis of P by CL in the GnRH-Ag-treated rats decreased to 40 +/- 14 from 138 +/- 54 ng/CL in controls, T and E levels were not different from their respective controls. Steroid levels in the ovarian vein plasma reflected a similar response. Nuclear E receptors levels were 211 and 198 in controls and 62 and 61 fmoles/mg DNA in the treated group on Days 12 and 14, respectively. These results suggest that GnRH-Ag has no effect on the ability of the luteal synthesis of T and E and that the anti-pregnancy effect of GnRH-Ag may be at the level of the CL due to the direct inhibitory effect of GnRH-Ag on the luteal synthesis of P which, in turn, results in a fall in E receptors in the CL. Alternatively, GnRH-Ag treatment could suppress luteal receptors for rat placental lactogen that, in turn, lower luteal E receptors, leading to a fall in luteal synthesis and release of P.
authors.affiliation: Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: R
authors.initials: R
authors.lastname: Sridaran
authors.forename: V B
authors.initials: VB
authors.lastname: Mahesh
mesh_terms: D000019:Abortifacient Agents / Q000494:pharmacology*; D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D010053:Ovary / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011959:Receptors, Estradiol / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D011959:Receptors, Estradiol; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C030741:lutrelin acetate