title: Impact of isotype-selective estrogen receptor agonists on ovarian function.
abstract: Other isotype-selective estrogen receptor (ER) agonists, the selective ERalpha agonist 3,17-dihydroxy-19-nor-17alpha-pregna-1,3,5 (10)-triene-21,16alpha-lactone and the selective ERbeta agonist 8-vinylestra-1,3,5 (10)-triene-3,17beta-diol, were used in hypophysectomized rats, gonadotropin-releasing hormone antagonist-treated mice, as well as intact rats to elucidate the effects of isotype-selective estrogens on the physiology of folliculogenesis and ovulation. In hypophysectomized rats and gonadotropin-releasing hormone antagonist-treated mice, the ERbeta agonist caused stimulation of early folliculogenesis, a decrease in follicular atresia, induction of ovarian gene expression, and stimulation of late follicular growth, accompanied by an increase in the number of ovulated oocytes similar to 17beta-estradiol (E2). In contrast, the ERalpha agonist had little or no effect on these parameters, implying that direct estrogen effects on ovarian follicular development are mediated by ERbeta. In intact rats, E2 and the ERalpha agonist dose-dependently inhibited ovulation, in contrast to the ERbeta agonist. On the other hand, the ERbeta agonist did not stimulate uterine weight in intact rats, in contrast to E2 and the ERalpha agonist. This finding is in line with the assumption that estrogen mediated ovulation inhibition and stimulation of uterine growth are mediated by ERalpha but not by ERbeta
authors.affiliation: Schering AG, Müllerstrasse 170-178, D-13342 Berlin, Germany. christa.hegelehartung@schering.de
authors.forename: Christa
authors.initials: C
authors.lastname: Hegele-Hartung
authors.forename: Philip
authors.initials: P
authors.lastname: Siebel
authors.forename: Olaf
authors.initials: O
authors.lastname: Peters
authors.forename: Dirk
authors.initials: D
authors.lastname: Kosemund
authors.forename: Gerd
authors.initials: G
authors.lastname: Müller
authors.forename: Alexander
authors.initials: A
authors.lastname: Hillisch
authors.forename: Alexander
authors.initials: A
authors.lastname: Walter
authors.forename: Jörn
authors.initials: J
authors.lastname: Kraetzschmar
authors.forename: Karl-Heinrich
authors.initials: KH
authors.lastname: Fritzemeier
mesh_terms: D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D009929:Organ Size; D010053:Ovary / Q000378:metabolism / Q000502:physiology*; D010060:Ovulation; D051381:Rats; D011960:Receptors, Estrogen / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D014599:Uterus / Q000187:drug effects
chemical_list: D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone