McLean M P, Derick R J, Miller J B
Biol Reprod. 1987 May;36(4):854-63. doi: 10.1095/biolreprod36.4.854.
Although estradiol is the established luteotropic hormone in the rabbit, the corpus luteum also contains a luteinizing hormone (LH)-activated adenylate cyclase system and cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase, which suggests that LH and cAMP may play a physiological role in regulating luteal progesterone production. The present study examined whether human chorionic gonadotropin (hCG) and cAMP derivatives stimulate progesterone production by dispersed rabbit luteal cells in static and perifusion incubations. Results of this study show that progesterone production by rabbit luteal cells is significantly stimulated (p less than 0.05) by hCG concentrations at or greater than 0.1 IU/ml or by dibutyryl cAMP concentrations at or greater than 5 mM. Both agents produce maximal stimulations of approximately 4-fold. However, neither prostaglandin E2 or F2 alpha at concentrations of 0.1-3.0 micrograms/ml altered progesterone secretion. When luteal cells were incubated with maximal concentrations of hCG and lipoproteins together, the resultant progesterone secretion was additive. This suggests that the effects of hCG and lipoprotein are independent. Both responses could be blocked completely by cycloheximide (10(-4) M), and thus appear to be dependent on protein synthesis. The cholesterol derivative 25-hydroxycholesterol (20 micrograms/ml) partially overcame the steroidogenic block by cycloheximide, suggesting that transport of cholesterol, regardless of its origin, into mitochondria was an essential protein-mediated event in these cells. Inhibition of the side-chain-cleavage enzyme by aminoglutethamide blocked progesterone production by rabbit luteal cells in vitro. Although estradiol may dominate in the regulation of luteal progesterone production physiologically, this study clearly demonstrates that potential mechanisms do exist in the rabbit corpus luteum for cAMP-mediated stimulation of progesterone production in the rabbit.
虽然雌二醇是家兔中公认的促黄体激素，但黄体中也含有促黄体生成素（LH）激活的腺苷酸环化酶系统和环磷腺苷（cAMP）依赖性蛋白激酶，这表明LH和cAMP可能在调节黄体孕酮生成中发挥生理作用。本研究检测了人绒毛膜促性腺激素（hCG）和cAMP衍生物在静态和灌注培养中对分散的家兔黄体细胞孕酮生成的刺激作用。本研究结果表明，当hCG浓度达到或高于0.1 IU/ml或二丁酰cAMP浓度达到或高于5 mM时，家兔黄体细胞的孕酮生成受到显著刺激（p<0.05）。两种试剂均产生约4倍的最大刺激作用。然而，浓度为0.1 - 3.0微克/毫升的前列腺素E2或F2α均未改变孕酮分泌。当黄体细胞与最大浓度的hCG和脂蛋白一起孵育时，产生的孕酮分泌是相加的。这表明hCG和脂蛋白的作用是独立的。两种反应均可被环己酰亚胺（10⁻⁴ M）完全阻断，因此似乎依赖于蛋白质合成。胆固醇衍生物25 - 羟胆固醇（20微克/毫升）部分克服了环己酰亚胺对类固醇生成的阻断作用，这表明胆固醇无论其来源如何，向线粒体的转运是这些细胞中一个重要的蛋白质介导事件。氨鲁米特对侧链裂解酶的抑制作用阻断了体外培养的家兔黄体细胞的孕酮生成。虽然雌二醇在生理上可能在黄体孕酮生成的调节中占主导地位，但本研究清楚地表明，家兔黄体中确实存在cAMP介导的孕酮生成刺激的潜在机制。
