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Human Reproduction, Vol. 10, No. 10, pp. 2554-2559, 1995
© 1995 European Society of Human Reproduction and Embryology

research-article

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

C.R. Harlow1, D.J. Cahill, L.A. Maile, P.G. Wardle and M.G.R. Hull

University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital Southwell Street, Bristol BS2 8EG, UK

Correspondence: 1To whom correspondence should be addressed

Transforming growth factor a (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 folliclestimulating 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.

Key words: aromatase activity/granulosa cell/human/TGF{alpha}


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