Time-dependent effects of transforming growth factor {alpha} on aromatase activity in human granulosa cells

Transforming growth factor a (TGF) is implicated as a paracrinegrowth factor in the regulation of human granulosa cell function.To investigate this further, we have examined the actions ofTGF on the basal and folliclestimulating hormone (FSH)-stimulatedaromatase activity of human granulosa cells to determine howthis growth factor influences oestrogen biosynthesis in thefollicle. Granulosa cells from women having in-vitro fertilizationduring untreated or gonadotrophin-stimulated cycles were culturedfor 1–6 days in the presence or absence of FSH or TGFat a range of doses. Aromatase activity, expressed as oestradiolproduction, was determined after culture during a 3 h test period.After 2 days, TGF (1–300 ng/ml) decreased basal and FSH-stimulatedaromatase activity in a dose-dependent manner (ED50 = 3 ng/ml).In contrast, after 4 days, TGF enhanced both basal and FSH-stimulatedaromatase activity. Repeated experiments revealed a consistentpattern of inhibition on day 2, which was more marked in thepresence of FSH (reduction by 30.6 ± 9.1%, mean ±SEM; n = 14; P < 0.01), and stimulation on day 4 in boththe 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). Theresults provide further evidence that TGF is a paracrine factorin the control of oestrogen biosynthesis, but the actions canbe either inhibitory or stimulatory depending on the durationof exposure.