Müllerian inhibiting substance inhibits testosterone synthesis in adult rats.
Müllerian inhibiting substance inhibits testosterone synthesis in adult rats.
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DOI：
10.1002/j.1939-4640.2001.tb02577.x
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发表时间：
2001-09
影响因子：
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通讯作者：
V. Sriraman;Enmei Niu;J. Matias;P. K. Donahoe;D. Maclaughlin;M. P. Hardy;Mary M. Lee
中科院分区：
文献类型：
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作者：
V. Sriraman;Enmei Niu;J. Matias;P. K. Donahoe;D. Maclaughlin;M. P. Hardy;Mary M. Lee
苗勒管抑制物质（MIS）是一种性腺激素，在男性性分化期间引起苗勒管退化。出生后，MIS抑制未成熟Leydig细胞的增殖和分化，过表达MIS的转基因小鼠血清睾酮浓度降低。为了阐明MIS对出生后睾丸雄激素调节的影响，我们研究了成年Sprague-Dawley大鼠睾丸内和腹腔注射MIS后的睾酮合成。睾丸内MIS注射在4小时达到高局部MIS浓度（574.0 +/- 60.0 ng/mL），血清睾酮浓度相应下降至0.7 +/- 0.1 ng/mL，而腹膜内MIS为1.1 +/- 0.2 ng/mL，睾丸内溶媒（IT-Veh）为1.6 +/- 0.1 ng/mL（P <0.001）。睾丸内注射MIS（IT-MIS）导致血清和睾丸间质液MIS浓度比腹腔途径高得多。为了直接检查MIS处理的动物中的睾酮产生速率，我们从MIS和溶剂注射的睾丸中分离Leydig细胞。暴露于MIS的原代睾丸间质细胞的睾酮产生率较低，p450 c17（羟化酶/裂解酶）和促黄体生成素（LH）受体mRNA的表达较低，而不是溶剂注射对照组或非注射对侧睾丸。总之，睾丸内注射MIS通过降低睾酮生物合成速率引起血清睾酮浓度下降，证实MIS可调节成人间质细胞雄激素产生。MIS下调p450 c17和LH受体基因mRNA表达的能力表明，这种作用是转录介导的。这些数据表明，除了在男性生殖道的胚胎分化中的作用，MIS在出生后的睾丸中具有调节功能。我们的结论是，这样的功能之一是MIS直接抑制成年Leydig细胞类固醇。
Müllerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to 1.1 +/- 0.2 ng/mL with intraperitoneal MIS and 1.6 +/- 0.1 ng/mL with intratesticular vehicle (IT-Veh) (P < .001). Intratesticular administration of MIS (IT-MIS) resulted in much higher serum and testicular interstitial fluid MIS concentrations than the intraperitoneal route. To directly examine the testosterone production rate in MIS-treated animals, we isolated Leydig cells from MIS and vehicle-injected testes. Primary Leydig cells exposed to MIS had a lower testosterone production rate and decreased expression of p450c17 (hydroxylase/lyase) and luteinizing hormone (LH) receptor mRNAs than that of vehicle-injected controls or the noninjected contralateral testis. In conclusion, intratesticular administration of MIS caused a decline in serum testosterone concentrations by decreasing the rate of testosterone biosynthesis, confirming that MIS can regulate adult Leydig cell androgen production. The ability of MIS to down-regulate mRNA expression of the p450c17 and LH receptor genes suggests that this effect is mediated transcriptionally. These data indicate that, in addition to its role in embryonic differentiation of the male reproductive tract, MIS has a regulatory function in the postnatal testis. We conclude that one such function is for MIS to directly inhibit adult Leydig cell steroidogenesis.