Molecular and Cellular Endocrinology, 69 (1990) 1-8 Elsevier Scientific Publishers Ireland. Ltd. 1 MOLCEL 02216 The effect of bovine activin and follicle-stimulating hormone (FSH) suppressing protein/follistatin on FSH-induced differentiation of rat granulosa cells in vitro S. Xiao I, J.K. Findlay ’ and D.M. Robertson 2 ’ Medical Research Centre, Prince Henry’s Campus, Monash Medical Centre, Melbourne, Vie. 3004, Australia, and 2 Department of Anatomy, Monash University, Clayton, Vie. 3168, Australia (Received 14 June 1989; accepted 28 October 1989) Key wora!x Granulosa cell; Activin; Follicle-stimulating hormone suppressing protein; Aromatase activity; Progesterone production; Inhibin production; (Rat) zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Summary zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA The time- and dose-dependent effects of bovine activin A and bovine follicle stimulating hormone (FSH) suppressing protein (FSP) or follistatin on basal and FSH-induced steroidogenesis and inhibin production were studied in granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of rat FSH (20 ng/ ml) which stimulates aromatase activity and the production of progesterone and inhibin, activin (0.3-100 ng/ ml) augmented all three parameters, whereas FSP (0.3-100 ng/ ml) enhanced progesterone production and attenuated the other two parameters. In the absence of FSH, the basal parameters were unaffected by treatment with either activin or FSP alone, except for a statistically significant increase in basal inhibin in the presence of activin alone (P < 0.05, at doses of 30 and 100 ng/ ml). Neither activin nor FSP influenced the timing of the maxima of FSH-induced activities over 5 days. These findings suggest that activin and FSP, both present in follicular fluid, may play an important role in the local regulation of granulosa cell differentiation. Introduction Although the central role of gonadotropins in the regulation of folliculogenesis is well estab- lished (Richards, 1979), there is increasing evi- dence that the action of gonadotropins can be modified at the local level by intragonadal peptides (Findlay and Risbridger, 1987; Findlay et al., 1987). It is possible that local intragonadal regu- Address for correspondence: Dr. Xiao Sai, Medical Re- search Centre, Prince Henry’s Campus, St. ICilda Road, Melbourne, Vie. 3004, Australia. lation is involved in selection of the dominant follicle(s). Inhibin and activin, two putative intragonadal regulatory substances, were purified from mam- malian follicular fluids (i&bin (Ling et al., 1985; Miyamato et al., 1985; Rivier et al., 1985; Robert- son et al., 1985, 1986; Fukuda et al., 1986; Leversha et al., 1987), activin (Ling et al., 1986; Vale et al., 1986)) and identified initially as an inhibitor and a stimulator respectively of pituitary follicle-stimulating hormone (FSH) secretion. Activin, which is a homodimer of two PA-chains of inhibin (activin A) or a heterodimer of the PA and PB chains (activin AB), has been shown to 0303-7207/90/$03.50 0 1990 Elsevier Scientific Publishers Ireland, Ltd.