title: Inhibitory effect of 5-alpha-dihydroprogesterone on nuclear estrogen receptor binding of the anterior pituitary and uterus in the rat.
abstract: Progesterone and its metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) have been shown to bring about gonadotropin release in the estrogen-primed ovariectomized rat. One of the actions of progesterone is the decrease in occupied estrogen receptors (E2Rs) in the anterior pituitary and uterus. This study attempted to determine if 5 alpha-DHP had a similar effect on pituitary and uterine E2Rs. Estrogen-primed ovariectomized mature female rats were injected with either vehicle, or 0.2, 0.8 or 2 mg/kg body weight (BW) of 5 alpha-DHP, 2 h before sacrifice and 1 h before the last estradiol injection (2 micrograms/rat). Nuclear E2Rs were determined by Scatchard analyses in the uterus and anterior pituitary. Total nuclear E2R levels of both tissues showed a 2-fold increase in the number of estradiol-binding sites after estradiol administration, as compared to control groups. In estradiol-primed rats, 5 alpha-DHP produced a significant decrease in total nuclear E2R levels in a tissue-specific manner. In the pituitary, there was a maximal and significant decrease in nuclear E2Rs with 0.2 and 2.0 mg/kg BW of 5 alpha-DHP as compared to estradiol alone; the intermediate dose of 0.8 mg/kg BW of 5 alpha-DHP induced a smaller nonsignificant change in nuclear E2Rs. In the uterus, 5 alpha-DHP showed a dose-dependent decrease in nuclear E2Rs. The 5 alpha-DHP effect in both tissues was due to a specific reduction in the occupied form of nuclear E2Rs levels. The unoccupied form of E2Rs was unaffected by 5 alpha-DHP administration. 5 alpha-DHP did not have any effect in the absence of estrogen priming.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology and Endocrinology, Medical College of Georgia, Augusta.
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: D043582:5-alpha-Dihydroprogesterone; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000648:ultrastructure; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D011277:Pregnanediones; D011960:Receptors, Estrogen; D004958:Estradiol; D043582:5-alpha-Dihydroprogesterone