REGULATION OF PORCINE GRANULOSA-CELL PROLIFERATION AND DIFFERENTIATION IN CULTURE BY PURIFIED HUMAN ALPHA-FETOPROTEIN - EFFECTS OF LOW-DENSITY-LIPOPROTEIN

We investigated the effects of purified human alpha-fetoprotein (AFP) on growth factor- and FSH-stimulated estradiol and progesterone produc tion and cell growth in the same primary cultures of porcine granulosa cells (pGC). Treatment of pGC with TGF alpha + IGF-I or FSH + ICF-I i ncreased estradiol production in the absence of hLDL, while hLDL dose- dependently decreased estradiol production in both treatment groups. A FP further diminished estradiol production in both groups at all doses of hLDL. With increasing hLDL, an inverse relationship between growth factor-mediated cell growth and production of both estradiol and prog esterone was observed, and AFP further augmented these effects. AFP ca used a significant (P<0.05) inhibition of progesterone secretion at ea ch dose of hLDL. Although AFP did not increase pGC proliferation in re sponse to FSH + ICF-I, the morphology of these cells was more consiste nt with actively dividing cells. These results suggest that: (1) AFP s ignificantly enhances growth factor-mediated cell growth while inhibit ing estradiol production, (2) hLDt dose-dependently increases cell gro wth while inhibiting estradiol production, (3) the effects of AFP are significantly and dose-dependently augmented by hLDL. These findings a dd further support for a novel role of AFP in modulating the prolifera tion and differentiation of cells.