Purified alpha fetoprotein (AFP) synergizes with transforming growth factor alpha (TGXa) and insulin-like growth factor I (IGF-I) to enhance proliferation of porcine granulosa cells (pGC) in primary culture, suggesting a role for AFP in the modulation of growth factor-mediated cell growth. TGFa stimulates basal estrogen production by pGC and is in fact more potent than FSH in these cells. In this study, we investigated the effects of AFP on growth factor-stimulated estradiol (EZ) production by pGC. Besal production of E2 was not alteredby the addition of AFP. AFP dose-dependently inhibited TGFa-stimulated E2 production with statistically significant inhibition observed with 2.5 pg/ml. We have previously shown that the mitogenic effects of AFP are maximized with TGFa+IGF-I. E2 production was even more sensitive to AFP inhibition when the two growth factors were combined. Human serum albumin (MA; 10 μg/ml) was without effect. AFP did not interfere with the E2 RIA, affect the uptake of 01 display specific in vitro binding of the androgen substrate. Furthermore, human AFP and HSA did not exhibit specific in vitro-of E2, in contrast to purified rat AFP (positive control). These data indicate that physiolq~ncentrations of purified AFP significantiy and dose-dependently inhibit growth factor-stimulated E2 production by pGC in culture. Since AFP is kr, I to increase KFa+IGF-I mediated cell growth, these data suggest that AFP may be inhibiting the differen iated function (steroidogenesis) of pGC while enhancing the proliferation of these cells.
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