Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
J Endocrinol. 2012 Oct;215(1):167-75. doi: 10.1530/JOE-12-0293. Epub 2012 Aug 7.
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 of FGF9 mRNA 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 of LHCGR, CYP11A1, and CYP17A1 mRNA (via real-time RT-PCR) in TCs. FGF9 had no effect (P>0·10) on STAR mRNA 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 of FGF9 mRNA 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 of FGF9 mRNA in TCs. In summary, expression of FGF9 mRNA 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.
成纤维细胞生长因子 9（FGF9）蛋白影响颗粒细胞（GC）功能，但主要定位于大鼠卵巢的卵泡膜细胞（TC）和基质细胞。本研究的目的是确定 1）FGF9 对 TC 类固醇生成、基因表达和细胞增殖的影响；2）FGF9 对 TC 的作用机制；以及 3）TC 中 FGF9 mRNA 表达的激素控制。从当地屠宰场采集牛卵巢，从大（8-22mm）卵泡中采集 TC，并在无血清培养基中用各种激素处理 24 或 48 小时。FGF9 导致 LH 和 LH+IGF1 诱导的雄烯二酮和孕酮产生呈剂量依赖性抑制（P<0·05）。此外，FGF9 抑制了 LH+IGF1 诱导的 TC 中 LHCGR、CYP11A1 和 CYP17A1 mRNA 的表达（通过实时 RT-PCR）（P<0·05）。FGF9 对 STAR mRNA 丰度没有影响（P>0·10）。此外，FGF9 抑制了 LH+IGF1 处理的 TC 中 dibutyryl cAMP 诱导的孕酮和雄烯二酮产生。相比之下，FGF9 增加了（P<0·05）牛 TC 的数量。GC 和 TC 中的 FGF9 mRNA 丰度在小（1-5mm）卵泡中比大卵泡中高几个数量级（P<0·05）。肿瘤坏死因子-α和 WNT5A 增加了（P<0·05）TC 中 FGF9 mRNA 的丰度。总之，TC 中 FGF9 mRNA 的表达受发育和激素调节。FGF9 可能通过抑制 LH+IGF1 作用来减缓 TC 分化，从而作为牛卵巢功能的自分泌调节剂，通过减少促性腺激素受体和 cAMP 信号级联，同时刺激 TC 增殖。
