Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH.
Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH.
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DOI：
10.1530/jme-16-0152
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发表时间：
2016-11
影响因子：
3.5
通讯作者：
J. J. Allen-J.;S. L. Herrick;J. E. Fortune
中科院分区：
文献类型：
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作者：
J. J. Allen-J.;S. L. Herrick;J. E. Fortune
在牛中，原始卵泡在出生前形成。胎儿卵巢产生孕酮和雌二醇的能力在卵泡形成前很高，在卵泡首次出现时（妊娠90天左右）下降。然而，在此期间调节类固醇产生的机制仍不清楚。我们假设LH刺激孕酮和雄激素的产生，FSH刺激雄激素芳构化为雌二醇。为了验证这一点，我们培养了10天的胎牛卵巢片没有或有外源性激素，然后通过RIA测量类固醇在培养基中的积累。LH（100 ng/mL）单独增加孕酮，雄烯二酮，睾酮和雌二醇的积累。FSH（100 ng/mL）单独增加孕酮和雌二醇的积累，但对雄激素没有影响。单独使用外源性睾酮（0.5 µM）可显著增加雌二醇蓄积，而睾酮+ FSH（但不是睾酮+ LH）联合使用可增加雌二醇相对于单独使用睾酮。有趣的是，外源性睾酮和雌二醇以剂量依赖性方式降低孕酮积累。由于最高剂量的雌二醇（0.5 µM）降低了孕酮的积累，但在相同的培养物中增加了双烯醇酮和雄烯二酮，内源性雌二醇可能是类固醇合成的旁分泌调节剂。总之，这些结果证实了我们最初的假设，并表明LH通过Δ5途径刺激胎牛卵巢中的雄激素产生，而FSH刺激雄激素芳构化为雌二醇。这些结果与牛排卵前卵泡雌二醇产生的双细胞、双促性腺激素模型一致，表明调节卵巢类固醇产生的机制在胎儿期建立。
In cattle, primordial follicles form before birth. Fetal ovarian capacity to produce progesterone and estradiol is high before follicle formation begins and decreases around the time follicles first appear (around 90 days of gestation). However, mechanisms that regulate steroid production during this time remain unclear. We hypothesized that LH stimulates progesterone and androgen production and that FSH stimulates aromatization of androgens to estradiol. To test this, we cultured pieces from fetal bovine ovaries for 10 days without or with exogenous hormones and then measured the accumulation of steroids in the culture medium by RIA. LH (100 ng/mL) alone increased the accumulation of progesterone, androstenedione, testosterone and estradiol. FSH (100 ng/mL) alone increased both progesterone and estradiol accumulation, but had no effect on androgens. Exogenous testosterone (0.5 µM) alone greatly increased estradiol accumulation and the combination of testosterone + FSH, but not testosterone + LH, increased estradiol relative to testosterone alone. Interestingly, exogenous testosterone and estradiol decreased progesterone accumulation in a dose-dependent manner. Because the highest dose of estradiol (0.5 µM) decreased progesterone accumulation, but increased both pregnenolone and androstenedione in the same cultures, endogenous estradiol may be a paracrine regulator of steroid synthesis. Together, these results confirm our initial hypotheses and indicate that LH stimulates androgen production in fetal bovine ovaries via the Δ5 pathway, whereas FSH stimulates aromatization of androgens to estradiol. These results are consistent with the two-cell, two-gonadotropin model of estradiol production by bovine preovulatory follicles, which suggests that the mechanisms regulating ovarian steroid production are established during fetal life.