title: Role of 17 beta-hydroxysteroid dehydrogenase in the modulation of nuclear estradiol receptor binding by progesterone in the rat anterior pituitary gland and the uterus.
abstract: Progesterone has been shown to decrease occupied pituitary and uterine nuclear estradiol receptor (E2R) binding in mature and immature estrogen-primed rats. Progesterone has also been shown to stimulate pituitary but not uterine 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in the rat. The conversion of estradiol to its less active metabolite estrone by 17 beta-HSD and activation of phosphatase are among mechanisms considered to be involved in the reduction of E2R. To determine if 17 beta-HSD stimulation was a mechanism by which progesterone induced nuclear E2R decrease, the synthetic estrogen ethinylestradiol, which is not oxidized by 17 beta-HSD, was used instead of estradiol to prime adult ovariectomized rats. When ethinylestradiol-primed rats received 0.8, 2.0 or 4.0 mg/kg body wt of progesterone 2 h before sacrifice, the total and occupied nuclear E2R accumulation in the anterior pituitary by a subsequent ethinylestradiol injection 1 h later did not show any decrease. This response was different from that observed previously in estradiol-primed animals in which progesterone showed a multiphasic decrease of occupied form of nuclear E2R. However, in the uterus of ethinylestradiol-primed rats, a partial decrease of total and occupied nuclear E2R accumulation was observed in the presence of the three doses of progesterone used. The decrease of uterine nuclear E2R with the three progesterone doses was different from the dose-dependent effect of progesterone observed in the uterus of estradiol-primed rats. Affinity constants of the interaction between [3H]estradiol and the nuclear E2R were similar among groups treated with ethinylestradiol, estradiol and progesterone. These results demonstrate the involvement of 17 beta-HSD in the reduction of anterior pituitary gland E2R by progesterone in the estradiol-treated animals. Furthermore, the mechanism of decrease of E2R by progesterone in the uterus appears to be different from the pituitary gland.
authors.affiliation: Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912.
authors.forename: M A
authors.initials: MA
authors.lastname: Fuentes
authors.forename: T G
authors.initials: TG
authors.lastname: Muldoon
authors.forename: V B
authors.initials: VB
authors.lastname: Mahesh
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D004967:Estrogens / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011959:Receptors, Estradiol / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: D004967:Estrogens; D011959:Receptors, Estradiol; D004997:Ethinyl Estradiol; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; D010744:Phosphoric Monoester Hydrolases