title: Interaction of prostaglandin F2alpha and gonadotropin-releasing hormone on progesterone and estradiol production in human granulosa-luteal cells.
abstract: This study examined the effects of prostaglandin-F2alpha (PGF2alpha), GnRH, and their interactions on steroidogenesis in human granulosa-luteal cells (GLCs). Human GLCs collected from in vitro fertilization patients were cultured for one or eight days, followed by a 24-h treatment period, after which media were collected and radioimmunoassayed for progesterone and estradiol. In the first experiment, GLCs were treated with vehicle, PGF2alpha (10(-9) M), GnRH (10(-6) M), or PGF2alpha plus GnRH, with or without hCG (1 IU/ml). Neither PGF2alpha nor GnRH alone had a significant effect; however, the combination of PGF2alpha plus GnRH significantly stimulated steroidogenesis. Similarly, co-application enhanced the luteolytic effects of PGF2alpha. In a second experiment, PGF2alpha and GnRH concentration-response curves were crossed into a matrix of 49 separate treatments. Responses were plotted in three-dimensions and as two-dimensional "slices" that were analyzed statistically. In the presence of high concentrations of GnRH (10(-6) M), PGF2alpha stimulated progesterone production in a biphasic manner, as middle concentrations significantly stimulated (10(-9) M) whereas low and high concentrations did not. In the presence of middle concentrations of PGF2alpha (10(-9) M), GnRH significantly stimulated progesterone production in a linear concentration-dependent manner. Similar complexities were seen with respect to estradiol response. Thus, in the human GLC, GnRH potentiates the luteolytic effects of PGF2alpha, while it acts as a permissive factor for the luteotropic effects. Furthermore, we have revealed the complex interaction of these hormones using a three-dimensional experimental design.
authors.affiliation: Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada.
authors.forename: J E
authors.initials: JE
authors.lastname: Väänänen
authors.forename: B L
authors.initials: BL
authors.lastname: Tong
authors.forename: C M
authors.initials: CM
authors.lastname: Väänänen
authors.forename: I H
authors.initials: IH
authors.lastname: Chan
authors.forename: B H
authors.initials: BH
authors.lastname: Yuen
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015237:Dinoprost / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*
chemical_list: D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D004247:DNA; D015237:Dinoprost