PMID- 8567769 OWN - NLM STAT- MEDLINE DCOM- 19960301 LR - 20190512 IS - 0268-1161 (Print) IS - 0268-1161 (Linking) VI - 10 IP - 10 DP - 1995 Oct TI - Time-dependent effects of transforming growth factor alpha on aromatase activity in human granulosa cells. PG - 2554-9 AB - 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. FAU - Harlow, C R AU - Harlow CR AD - University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital, UK. FAU - Cahill, D J AU - Cahill DJ FAU - Maile, L A AU - Maile LA FAU - Wardle, P G AU - Wardle PG FAU - Hull, M G AU - Hull MG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Transforming Growth Factor alpha) RN - 4TI98Z838E (Estradiol) RN - 9002-68-0 (Follicle Stimulating Hormone) RN - EC 1.14.14.1 (Aromatase) SB - IM MH - Aromatase/*metabolism MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Estradiol/biosynthesis MH - Female MH - Fertilization in Vitro MH - Follicle Stimulating Hormone/pharmacology MH - Granulosa Cells/drug effects/*enzymology MH - Humans MH - Kinetics MH - Transforming Growth Factor alpha/administration & dosage/*pharmacology EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] AID - 10.1093/oxfordjournals.humrep.a135744 [doi] PST - ppublish SO - Hum Reprod. 1995 Oct;10(10):2554-9. doi: 10.1093/oxfordjournals.humrep.a135744.