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胎牛卵巢中类固醇生成的调节:促黄体生成素(LH)和促卵泡生成素(FSH)的不同作用

Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH.

作者信息

Allen J J, Herrick S L, Fortune J E

机构信息

Department of Biomedical SciencesCornell University, Ithaca, New York, USA

Department of Biomedical SciencesCornell University, Ithaca, New York, USA.

出版信息

J Mol Endocrinol. 2016 Nov;57(4):275-286. doi: 10.1530/JME-16-0152. Epub 2016 Oct 3.

Abstract

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 Δ 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.

摘要

在牛中,原始卵泡在出生前形成。在卵泡形成开始前,胎儿卵巢产生孕酮和雌二醇的能力较高,而在卵泡首次出现时(约妊娠90天)下降。然而,在此期间调节类固醇生成的机制仍不清楚。我们假设促黄体生成素(LH)刺激孕酮和雄激素的产生,而促卵泡生成素(FSH)刺激雄激素向雌二醇的芳香化。为了验证这一点,我们将胎牛卵巢组织块在无或有外源激素的情况下培养10天,然后通过放射免疫分析法(RIA)测量培养基中类固醇的积累。单独使用LH(100 ng/mL)可增加孕酮、雄烯二酮、睾酮和雌二醇的积累。单独使用FSH(100 ng/mL)可增加孕酮和雌二醇的积累,但对雄激素无影响。单独使用外源睾酮(0.5 μM)可大大增加雌二醇的积累,睾酮+FSH的组合相对于单独使用睾酮增加了雌二醇,但睾酮+LH的组合没有。有趣的是,外源睾酮和雌二醇以剂量依赖的方式降低了孕酮的积累。由于最高剂量的雌二醇(0.5 μM)降低了孕酮的积累,但在相同培养物中增加了孕烯醇酮和雄烯二酮,内源性雌二醇可能是类固醇合成的旁分泌调节因子。总之,这些结果证实了我们最初的假设,并表明LH通过Δ途径刺激胎牛卵巢中雄激素的产生,而FSH刺激雄激素向雌二醇的芳香化。这些结果与牛排卵前卵泡产生雌二醇的双细胞、双促性腺激素模型一致,这表明调节卵巢类固醇产生的机制在胎儿期就已建立。

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