糖皮质激素体外诱导睾丸雄激素生物合成抑制的机制。

Mechanism of glucocorticoid-induced suppression of testicular androgen biosynthesis in vitro.

作者信息

Welsh T H, Bambino T H, Hsueh A J

出版信息

Biol Reprod. 1982 Dec;27(5):1138-46. doi: 10.1095/biolreprod27.5.1138.

DOI:10.1095/biolreprod27.5.1138

Abstract

The mechanism whereby glucocorticoids directly inhibit gonadotropin-stimulated testosterone production was studied by using primary cultures of testicular cells from adult hypophysectomized rats. Testicular cells were maintained in serum-free media with hormone treatments administered on Day 8 and media collected 48 h later for steroid and cAMP measurement. Highly purified human chorionic gonadotropin (hCG) increased testosterone production relative to controls. Concomitant administration of either natural (cortisone greater than deoxycorticosterone = aldosterone) or synthetic (dexamethasone greater than or equal to prednisolone) corticosteroids inhibited hCG-stimulated testosterone production in a dose-dependent manner. Dexamethasone at 10(-7) M decreased testosterone production by approximately 50-60% and this inhibitory effect was reversible upon removal of the glucocorticoid. In the presence or absence of a phosphodiesterase inhibitor, dexamethasone decreased hCG-stimulated cAMP production by approximately 60%. Dexamethasone also decreased testosterone production induced by cholera toxin and (Bu)2 cAMP by 43 and 63%, respectively. The dexamethasone suppression of testosterone production was accompanied by marked decreases in androstenedione (80% decrease) and 17 alpha-hydroxyprogesterone (57%) production, with a lesser effect on progesterone production (28% decrease) and no effect on pregnenolone production. Exogenous progesterone and 17 alpha-hydroxyprogesterone augmented hCG-stimulated testosterone production. Dexamethasone reduced the conversion of exogenous progesterone to testosterone by 33% but did not affect the conversion of 17 alpha-hydroxyprogesterone to androstenedione and testosterone, suggesting a specific inhibition of 17 alpha-hydroxylase. These results suggest that glucocorticoids directly suppress Leydig cell steroidogenesis by decreasing gonadotropin stimulation of cAMP production and the activity of 17 alpha-hydroxylase.

摘要

利用成年去垂体大鼠的睾丸细胞原代培养物，研究了糖皮质激素直接抑制促性腺激素刺激的睾酮生成的机制。将睾丸细胞置于无血清培养基中，在第8天进行激素处理，48小时后收集培养基用于类固醇和环磷酸腺苷（cAMP）测定。与对照组相比，高度纯化的人绒毛膜促性腺激素（hCG）可增加睾酮生成。同时给予天然皮质类固醇（可的松＞脱氧皮质酮 = 醛固酮）或合成皮质类固醇（地塞米松≥泼尼松龙）均以剂量依赖方式抑制hCG刺激的睾酮生成。10⁻⁷M的地塞米松可使睾酮生成减少约50 - 60%，且去除糖皮质激素后这种抑制作用是可逆的。在存在或不存在磷酸二酯酶抑制剂的情况下，地塞米松可使hCG刺激的cAMP生成减少约60%。地塞米松还分别使霍乱毒素和（Bu）₂cAMP诱导的睾酮生成减少43%和63%。地塞米松对睾酮生成的抑制伴随着雄烯二酮生成显著减少（减少80%）和17α - 羟孕酮生成减少（57%），对孕酮生成的影响较小（减少28%），对孕烯醇酮生成无影响。外源性孕酮和17α - 羟孕酮可增强hCG刺激的睾酮生成。地塞米松使外源性孕酮向睾酮的转化减少33%，但不影响17α - 羟孕酮向雄烯二酮和睾酮的转化，提示对17α - 羟化酶有特异性抑制作用。这些结果表明，糖皮质激素通过减少促性腺激素对cAMP生成的刺激以及17α - 羟化酶的活性，直接抑制睾丸间质细胞的类固醇生成。