Purified human alpha fetoprotein inhibits growth factor-stimulated estradiol production by porcine granulosa cells in monolayer culture.
Purified alpha fetoprotein (AFP) synergizes with transforming growth factor alpha (TGF alpha) 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. TGF alpha 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 (E2) production by pGC. Basal production of E2 was not altered by the addition of AFP. AFP dose-dependently inhibited TGF alpha-stimulated E2 production with statistically significant inhibition observed with 2.5 micrograms/ml. We have previously shown that the mitogenic effects of AFP are maximized with TGF alpha+IGF-I. E2 production was even more sensitive to AFP inhibition when the two growth factors were combined. Human serum albumin (HSA; 10 micrograms/ml) was without effect. AFP did not interfere with the E2 RIA, affect the uptake of or display specific in vitro binding of the androgen substrate. Furthermore, human AFP and HSA did not exhibit specific in vitro binding of E2, in contrast to purified rat AFP (positive control). These data indicate that physiological concentrations of purified AFP significantly and dose-dependently inhibit growth factor-stimulated E2 production by pGC in culture. Since AFP is known to increase TGF alpha+IGF-I mediated cell growth, these data suggest that AFP may be inhibiting the differentiated function (steroidogenesis) of pGC while enhancing the proliferation of these cells.
Keel
B A
BA
Department of Obstetrics and Gynecology, University of Kansas School of Medicine-Wichita 67214.
Eddy
K B
KB
Cho
S
S
Gangrade
B K
BK
May
J V
JV
D000653:Amniotic Fluid; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013552:Swine; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
D012709:Serum Albumin; D016211:Transforming Growth Factor alpha; D000509:alpha-Fetoproteins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I