Expression and effect of fibroblast growth factor 9 in bovine theca cells

Abstract

Fibroblast growth factor 9 (FGF9) protein affects granulosa cell (GC) function but is mostly localized to theca cell (TC) and stromal cell of rat ovaries. The objectives of this study were to determine the 1) effects of FGF9 on TC steroidogenesis, gene expression, and cell proliferation; 2) mechanism of action of FGF9 on TCs; and 3) hormonal control ofFGF9mRNA expression in TCs. Bovine ovaries were collected from a local slaughterhouse and TCs were collected from large (8–22 mm) follicles and treated with various hormones in serum-free medium for 24 or 48 h. FGF9 caused a dose-dependent inhibition (P<0.05) of LH- and LH+IGF1-induced androstenedione and progesterone production. Also, FGF9 inhibited (P<0.05) LH+IGF1-induced expression ofLHCGR,CYP11A1, andCYP17A1mRNA (via real-time RT-PCR) in TCs. FGF9 had no effect (P>0.10) onSTARmRNA abundance. Furthermore, FGF9 inhibited dibutyryl cAMP-induced progesterone and androstenedione production in LH+IGF1-treated TCs. By contrast, FGF9 increased (P<0.05) the number of bovine TCs. Abundance ofFGF9mRNA in GCs and TCs was several-fold greater (P<0.05) in small (1–5 mm) vs large follicles. Tumor necrosis factor α and WNT5A increased (P<0.05) abundance ofFGF9mRNA in TCs. In summary, expression ofFGF9mRNA in TCs is developmentally and hormonally regulated. FGF9 may act as an autocrine regulator of ovarian function in cattle by slowing TC differentiation via inhibiting LH+IGF1 action via decreasing gonadotropin receptors and the cAMP signaling cascade while stimulating proliferation of TCs.