title: Time-dependent effects of transforming growth factor alpha on aromatase activity in human granulosa cells.
abstract: Transforming growth factor alpha (TGF alpha) is implicated as a paracrine growth factor in the regulation of human granulosa cell function. To investigate this further, we have examined the actions of TGF alpha on the basal and follicle-stimulating hormone (FSH)-stimulated aromatase activity of human granulosa cells to determine how this growth factor influences oestrogen biosynthesis in the follicle. Granulosa cells from women having in-vitro fertilization during untreated or gonadotrophin-stimulated cycles were cultured for 1-6 days in the presence or absence of FSH or TGF alpha at a range of doses. Aromatase activity, expressed as oestradiol production, was determined after culture during a 3 h test period. After 2 days, TGF alpha (1-300 ng/ml) decreased basal and FSH-stimulated aromatase activity in a dose-dependent manner (ED50 = 3 ng/ml). In contrast, after 4 days, TGF alpha enhanced both basal and FSH-stimulated aromatase activity. Repeated experiments revealed a consistent pattern of inhibition on day 2, which was more marked in the presence of FSH (reduction by 30.6 +/- 9.1%, mean +/- SEM; n = 14; P < 0.01), and stimulation on day 4 in both the absence (increased by 61.4 +/- 20.6%, mean +/- SEM; n = 6; P < 0.05) and presence of FSH (increased by 36.0 +/- 15.2%, mean +/- SEM; n = 8; P < 0.05). The results provide further evidence that TGF alpha is a paracrine factor in the control of oestrogen biosynthesis, but the actions can be either inhibitory or stimulatory depending on the duration of exposure.
authors.affiliation: University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Harlow
authors.forename: D J
authors.initials: DJ
authors.lastname: Cahill
authors.forename: L A
authors.initials: LA
authors.lastname: Maile
authors.forename: P G
authors.initials: PG
authors.lastname: Wardle
authors.forename: M G
authors.initials: MG
authors.lastname: Hull
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D016211:Transforming Growth Factor alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016211:Transforming Growth Factor alpha; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D001141:Aromatase