EVIDENCE FOR THE INVOLVEMENT OF NONANDROGENIC TESTICULAR FACTORS IN THE REGULATION OF HYPOTHALAMIC SOMATOSTATIN AND GHRH MESSENGER-RNA LEVELS

The growth hormone (GH) secretory pattern is dependent on sex and deve lopmental stage. It is generally accepted that in the male rat this pa ttern is markedly influenced by androgens secreted by the Leydig cells . Recent findings, however, point to the existence of other non-androg enic testicular factors produced by the Sertoli cells and which regula te in vivo the GH responses to growth hormone releasing hormone (GHRH) . The aim of this work was to investigate the role played by non-andro genic testicular factors on hypothalamic somatostatin (SST) and GHRH m RNA levels. Seventy-day-old male Sprague-Dawley rats were used through out the work. They were divided into five groups: (1) control rats; (2 ) gonadectomized rats; (3) gonadectomized rats supplemented with exoge nous administration of dihydrotestosterone (DHT); (4) ethylene dimetha ne sulphonate (EDS)-treated rats; (5) EDS-treated rats supplemented wi th exogenous administration of DHT. EDS is a cytotoxic agent that spec ifically destroys the Leydig cells. The rats were killed after 15 days of treatment. Hypothalamic SST mRNA levels were determined by Norther n blot and by in situ hybridization, and GHRH mRNA levels assessed by Northern blot. We found that selective removal of Leydig cells with ED S 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 E DS-treated rats, contrasting with the complete recovery of SST mRNA le vels in gonadectomized rats. On the other hand, gonadectomy and EDS tr eatment produced a significant reduction in GHRH mRNA levels. DHT admi nistration reversed the action of gonadectomy, but did not restore GHR H mRNA content in EDS-treated rats. These data suggest that, in additi on to testosterone, as yet unidentified non-androgenic testicular fact ors can significantly influence SST and GHRH mRNA levels. This may ind icate that non-androgenic testicular factors acting at hypothalamic le vel may be important in the neuroregulation of GH secretion and in the maintenance of sexual dimorphism in GH secretory pattern.