Lago F, Señarís R M, Emson P C, Domínguez F, Diéguez C
Department of Physiology, University of Santiago de Compostela, Spain.
Brain Res Mol Brain Res. 1996 Jan;35(1-2):220-6.
The growth hormone (GH) secretory pattern is dependent on sex and developmental stage. It is generally accepted that in the male rat this pattern is markedly influenced by androgens secreted by the Leydig cells. Recent findings, however, point to the existence of other non-androgenic testicular factors produced by the Sertoli cells and which regulate in vivo the GH responses to growth hormone releasing hormone (GHRH). The aim of this work was to investigate the role played by non-androgenic testicular factors on hypothalamic somatostatin (SST) and GHRH mRNA levels. Seventy-day-old male Sprague-Dawley rats were used throughout the work. They were divided into five groups: (1) control rats; (2) gonadectomized rats; (3) gonadectomized rats supplemented with exogenous administration of dihydrotestosterone (DHT); (4) ethylene dimethane sulphonate (EDS)-treated rats; (5) EDS-treated rats supplemented with exogenous administration of DHT. EDS is a cytotoxic agent that specifically destroys the Leydig cells. The rats were killed after 15 days of treatment. Hypothalamic SST mRNA levels were determined by Northern blot and by in situ hybridization, and GHRH mRNA levels assessed by Northern blot. We found that selective removal of Leydig cells with EDS greatly reduced the SST mRNA content in the periventricular nucleus of the hypothalamus. These levels were significantly lower than those found in gonadectomized rats. Furthermore, replacement treatment with dihydrotesterone (DHT) did not completely restore SST mRNA levels in EDS-treated rats, contrasting with the complete recovery of SST mRNA levels in gonadectomized rats. On the other hand, gonadectomy and EDS treatment produced a significant reduction in GHRH mRNA levels. DHT administration reversed the action of gonadectomy, but did not restore GHRH mRNA content in EDS-treated rats. These data suggest that, in addition to testosterone, as yet unidentified non-androgenic testicular factors can significantly influence SST and GHRH mRNA levels. This may indicate that non-androgenic testicular factors acting at hypothalamic level may be important in the neuroregulation of GH secretion and in the maintenance of sexual dimorphism in GH secretory pattern.
生长激素（GH）的分泌模式取决于性别和发育阶段。一般认为，在雄性大鼠中，这种模式受到睾丸间质细胞分泌的雄激素的显著影响。然而，最近的研究结果表明，存在由支持细胞产生的其他非雄激素性睾丸因子，它们在体内调节GH对生长激素释放激素（GHRH）的反应。这项工作的目的是研究非雄激素性睾丸因子对下丘脑生长抑素（SST）和GHRH mRNA水平的作用。整个实验过程使用70日龄的雄性Sprague-Dawley大鼠。它们被分为五组：（1）对照大鼠；（2）去势大鼠；（3）去势大鼠补充外源性二氢睾酮（DHT）；（4）乙烯二甲磺酸酯（EDS）处理的大鼠；（5）EDS处理的大鼠补充外源性DHT。EDS是一种细胞毒性剂，能特异性地破坏睾丸间质细胞。处理15天后处死大鼠。通过Northern印迹法和原位杂交法测定下丘脑SST mRNA水平，通过Northern印迹法评估GHRH mRNA水平。我们发现，用EDS选择性去除睾丸间质细胞可大大降低下丘脑室周核中SST mRNA的含量。这些水平显著低于去势大鼠中的水平。此外，用二氢睾酮（DHT）替代治疗并未完全恢复EDS处理大鼠中的SST mRNA水平，这与去势大鼠中SST mRNA水平的完全恢复形成对比。另一方面，去势和EDS处理导致GHRH mRNA水平显著降低。给予DHT可逆转去势的作用，但不能恢复EDS处理大鼠中的GHRH mRNA含量。这些数据表明，除了睾酮外，尚未确定的非雄激素性睾丸因子可显著影响SST和GHRH mRNA水平。这可能表明，作用于下丘脑水平的非雄激素性睾丸因子在GH分泌的神经调节以及GH分泌模式的性别差异维持中可能很重要。
