Sharpe R M, Maddocks S
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, U.K.
Int J Androl. 1989 Aug;12(4):295-306. doi: 10.1111/j.1365-2605.1989.tb01317.x.
This study aimed to identify the role of endocrine (FSH, LH, testosterone) or paracrine (Leydig or germ cell) factors in control of the secretion of inhibin into testicular interstitial fluid (IF). This was done by measuring inhibin and testosterone levels in IF, and serum gonadotrophin and testosterone levels in adult rats following the destruction of Leydig cells with ethane dimethane sulphonate (EDS), alone or in combination with testosterone ester (TE) supplementation at various doses initiated at various times after EDS treatment. The effect of germ cell loss (induced by local testicular heating) on its own or in combination with the above treatments was also assessed. Treatment with EDS led to major increases in the levels of inhibin in IF and of FSH and LH in serum whilst testosterone levels in IF and serum fell to undetectable levels. Supplementation with TE (1-25 mg) for 21 days from the time of EDS treatment failed to prevent the initial (+3 days) increase in IF levels of inhibin but thereafter suppressed inhibin to control levels or lower and grossly suppressed FSH and LH levels, irrespective of whether the dose of TE administered did (25 or 5 mg) or did not (1 mg) prevent major seminiferous tubule damage. Partial regeneration of Leydig cells and normalization of testosterone levels occurred in rats 21 days after treatment with EDS alone but this failed to normalize inhibin and gonadotrophin levels. When supplementation with TE (25 mg) was initiated at 3, 6 or 9 days after EDS treatment, IF levels of inhibin were normalized within 3 days and maintained thereafter in parallel with suppression of serum FSH and LH to below control levels. Seminiferous tubule damage induced by local testicular heating (43 degrees C for 30 min) led to increased IF levels of inhibin 3 and 14 days later, in parallel with increased serum levels of FSH (but not LH). Suppression of FSH to subnormal levels in heat-exposed rats by TE treatment (25 mg) restored IF inhibin to control levels or below, a change which still occurred when Leydig cells were destroyed by EDS treatment. It is concluded that secretion of inhibin via the base of the Sertoli cell into testicular IF is controlled primarily by FSH, although local factors may play a minor role. These findings have important implications regarding the possible paracrine role(s) of inhibin in IF during puberty and in the normal adult testis.
本研究旨在确定内分泌因子（促卵泡激素、促黄体生成素、睾酮）或旁分泌因子（睾丸间质细胞或生殖细胞）在控制抑制素分泌到睾丸间质液（IF）中的作用。通过测量成年大鼠睾丸间质液中抑制素和睾酮水平，以及在使用乙烷二甲磺酸盐（EDS）破坏睾丸间质细胞后单独或联合不同剂量睾酮酯（TE）补充剂（在EDS处理后的不同时间开始）时血清促性腺激素和睾酮水平来实现这一目的。还评估了生殖细胞丢失（由局部睾丸加热诱导）单独或与上述处理联合的影响。用EDS处理导致睾丸间质液中抑制素水平以及血清中促卵泡激素和促黄体生成素水平大幅升高，而睾丸间质液和血清中的睾酮水平降至无法检测的水平。从EDS处理时起补充TE（1 - 25毫克）21天未能预防抑制素在睾丸间质液水平最初（+3天）的升高，但此后将抑制素抑制至对照水平或更低，并显著抑制促卵泡激素和促黄体生成素水平，无论给予的TE剂量（25毫克或5毫克）是否能预防（1毫克则不能）严重的生精小管损伤。单独用EDS处理21天后，大鼠睾丸间质细胞部分再生且睾酮水平恢复正常，但这未能使抑制素和促性腺激素水平恢复正常。当在EDS处理后3、6或9天开始补充TE（25毫克）时，睾丸间质液中抑制素水平在3天内恢复正常，并在随后与血清促卵泡激素和促黄体生成素被抑制至对照水平以下保持同步。局部睾丸加热（43摄氏度，30分钟）诱导的生精小管损伤导致3天和14天后睾丸间质液中抑制素水平升高，同时血清促卵泡激素水平升高（但促黄体生成素水平未升高）。用TE处理（25毫克）将受热大鼠的促卵泡激素抑制至低于正常水平，使睾丸间质液中抑制素恢复至对照水平或更低，当睾丸间质细胞被EDS处理破坏时这种变化仍然会发生。结论是，抑制素通过支持细胞基部分泌到睾丸间质液中主要受促卵泡激素控制，尽管局部因素可能起次要作用。这些发现对于青春期和正常成年睾丸中抑制素在睾丸间质液中可能的旁分泌作用具有重要意义。
