REPRODUCTIVE AGING OF HYPOTHALAMUS-PITUITARY-TESTICULAR AXIS IN MIDDLE-AGED MALE RATS

Abstract

Androgen deficiency, an indicator of reproductive aging in males, is not particularly detectable, though serum testosterone levels were gradually and progressively decreased with advancing age. The major organ of androgen production is testis which is regulated via hypothalamic-pituitary-testicular (HPT) axis. Thus, this study was to search when the reproductive aging can be detected in male rats during the transition into the middle age in association with alterations of pituitary luteinizing hormone (LH) production and transcript expression of reproductive hormone-related genes in hypothalamus. Male Sprague-Dawley rats at 4 (young age), 6, 8, 10 and 12 (middle age) months old were subjected for this study. In each age of rats, blood was collected for serum testosterone and LH assays, mRNA levels of gonadotropin releasing hormone (Gnrh1) gene at preoptic area (PoA), and kisspeptin (Kiss1) and androgen receptor (Ar) genes at anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) of hypothalamus were measured. Rats showed a significant reduction of serum testosterone level at 12 months old, though the levels were marginally decreased from 8 months old. Serum LH and PoA-Gnrh1 mRNA levels were significant declined from 8 months old. AVPV-Kiss1 mRNA level was significantly decreased at 12 months old. Ar mRNA levels in AVPV and ARC were significantly decreased from 8 and 10 months old, respectively. Our study depicts that reproductive aging can be first detected at middle age of male rats, and mechanisms of occurrence is initiated earlier (at 8 months old) by the deterioration at the hypothalamus and pituitary levels.