Effects of corticotropin-releasing hormone on ovarian estrogen production in vitro
Effects of corticotropin-releasing hormone on ovarian estrogen production in vitro
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DOI：
10.1210/en.137.10.4161
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发表时间：
1996-10-01
期刊：
影响因子：
4.8
通讯作者：
DAgata, R
中科院分区：
文献类型：
--
作者：
Calogero, AE;Burrello, N;DAgata, R
应激伴随着下丘脑-垂体-卵巢轴的功能障碍是一种常见的临床观察，越来越多的实验证据表明，作为ACTH释放的主要调节者和应激反应的中枢协调者，CRH能够通过抑制下丘脑GnRH的释放来抑制性腺功能。最近研究表明，CRH、CRH信使RNA和CRH受体也存在于卵巢中。这促使我们研究CRH在卵巢功能中的作用。为了实现这一点，我们研究了这种神经肽对大鼠颗粒细胞和人颗粒黄体细胞雌激素产生和细胞内cAMP含量的影响。我们还通过测量培养的大鼠颗粒细胞匀浆中氚水的产量来评估该酶芳香化酶的活性。CRH以剂量依赖的方式抑制FSH刺激的大鼠颗粒细胞雌激素的产生。浓度为10(-8)M时效果最好，抑制雌激素生成约30%。低浓度的CRH(10(-10)M)不能调节对FSH的最大雌激素产生，导致雌激素剂量-反应曲线向FSH右移。CRH(10(-8)M)抑制FSH孵育的大鼠颗粒细胞匀浆氚水的产生(相当于雌激素的产生)。CRH在10(-10)M时对人颗粒黄体细胞的基础雌激素产生也有抑制作用，其中以10(-8)M的作用最强，可使雌激素产生减少25%。CRH受体拮抗剂α-螺旋CRH-(9-41)可拮抗CRH对大鼠颗粒细胞和人颗粒黄体细胞产生雌激素的抑制作用，而单独应用则无明显作用。CRH对大鼠颗粒细胞和人颗粒黄体细胞内cAMP含量无明显影响，提示CRH在体外能抑制大鼠和人颗粒细胞产生雌激素。这种作用似乎与抑制大鼠的芳香酶活性有关，并且不依赖于cAMP的生成。我们推测CRH也可能通过直接作用于卵巢水平而干扰下丘脑-垂体-性腺轴的功能。
It is a common clinical observation that stress is accompanied by dysfunction of the hypothalamic-pituitary-ovarian axis, and there is mounting experimental evidence that CRH, the principal regulator of ACTH release and the central coordinator of the stress response, is able to suppress gonadal function by inhibiting hypothalamic GnRH release. Recently, it has been shown that immunoreactive CRH, CRH messenger RNA, and CRH receptors are also present in the ovary. This prompted us to examine the role of CRH on ovarian function. To accomplish this, we studied the effects of this neuropeptide on estrogen production and cAMP intracellular content from rat granulosa and human granulosa-luteal cells. We also evaluated the activity of the enzyme aromatase by measuring the production of tritiated water from homogenates of cultured rat granulosa cells. CRH inhibited FSH-stimulated estrogen production from rat granulosa cells in a dose-dependent fashion. The maximal effect was achieved at a concentration of 10(-8) M, which suppressed estrogen production by about 30%. Low concentrations of CRH (10(-10) M), incapable of modulating maximal estrogen production in response to FSH, provoked a right-ward shift of the estrogen dose-response curve to FSH. CRH (10(-8) M) suppressed the production of tritiated water (equivalent to estrogen production) from homogenates of rat granulosa cells incubated with a half-maximal concentration of FSH. Basal estrogen production by human granulosa-luteal cells was also inhibited by CRH at a concentration of 10(-10) M. The maximal effect was achieved with a concentration of 10(-8) M, which lowered estrogen production by 25%. The CRH receptor antagonist alpha-helical CRH-(9-41) antagonized the inhibitory effect of CRH on estrogen production from rat granulosa and human granulosa-luteal cells, whereas alone it had no effect. CRH did not have any effect on the intracellular cAMP content of rat granulosa and human granulosa-luteal cells.In conclusion, these results suggest that CRH is able to suppress estrogen production from rat and human granulosa cells in vitro. This effect seems to be linked to inhibition of aromatase activity in the rat and is independent of cAMP generation. We speculate that CRH may also interfere with hypothalamic-pituitary-gonadal axis function by acting directly at the ovarian level.