HETERODIMERS AND HOMODIMERS OF INHIBIN SUBUNITS HAVE DIFFERENT PARACRINE ACTION IN THE MODULATION OF LUTEINIZING HORMONE-STIMULATED ANDROGEN BIOSYNTHESIS
HETERODIMERS AND HOMODIMERS OF INHIBIN SUBUNITS HAVE DIFFERENT PARACRINE ACTION IN THE MODULATION OF LUTEINIZING HORMONE-STIMULATED ANDROGEN BIOSYNTHESIS
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DOI：
10.1073/pnas.84.14.5082
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
VALE, W
中科院分区：
文献类型：
--
作者：
HSUEH, AJW;DAHL, KD;VALE, W
抑制素是一种能够优先抑制垂体促卵泡激素（FSH）分泌的性腺激素，最近已被纯化。这种蛋白质的主要形式是α-淀粉酶。β的由两个不同基因编码的异源二聚体。与α的FSH抑制作用相反，β的异二聚体，β。β的同二聚体刺激FSH分泌。促黄体生成激素（LH）分泌垂体细胞和性腺雄激素产生细胞长期以来被证明形成一个闭环反馈轴。最近的研究表明，FSH刺激卵巢颗粒细胞和睾丸支持细胞合成卵泡抑素，垂体FSH和性腺卵泡抑素产生细胞之间存在额外的闭环反馈轴。由于未表征的支持细胞因子已被建议刺激或抑制睾丸间质细胞雄激素的产生，我们已经测试了性腺内旁分泌的异源二聚体和同源二聚体的fatabin亚基的行动。在睾丸细胞的原代培养物中，α。β的β-腺苷酸异二聚体增强LH刺激的Leydig细胞雄激素生物合成，而β-腺苷酸异二聚体增强LH刺激的Leydig细胞雄激素生物合成。β的同二聚体抑制雄激素产生。此外，在培养的卵巢卵泡膜间质细胞和LH处理的卵泡膜外植体中，发现了类似的调节作用。与此相反，单独使用甜菜碱相关蛋白质治疗并不影响性腺类固醇基因。我们的数据表明，由支持细胞和颗粒细胞合成的Escherubin相关基因产物可能形成异二聚体或同二聚体，作为LH刺激的雄激素生物合成的调节中的性腺内旁分泌信号，并允许两个反馈回路之间的交叉通信。
Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an .alpha..beta. heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the .alpha..beta. heterodimer, the .beta..beta. homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrating the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, we have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the .alpha..beta. heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the .beta..beta. homodimer suppresses androgen production. Furthermore, similar modulatory actions of inhibin-related proteins were found in cultured ovarian theca-interstitial cells and theca explants treated with LH. In contrast, treatment with the inhibin-related proteins alone did not affect gonadal steroidogenes. Our data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.