Elevated levels of inhibin-A and immunoreactive inhibin in aged male Wistar rats with testicular Leydig cell tumor

This study was undertaken to investigate the endocrine changes that occur i n male Tig:Wistar rats with Leydig cell tumors, with special reference to i mmunoreactive inhibin (ir-inhibin) and its dimeric forms. Adult male rats f rom 2 to 28 months of age were used. Blood samples were taken to measure pl asma concentrations of ir-inhibin, inhibin-A, inhibin-B, 17 beta -estradiol (E-2) testosterone, luteinizing hormone (LH), and follicle-stimulating hor mone (FSH). Inhibin bioactivity in both peripheral plasma and testicular ex tracts was also measured. Rats aged 18 months and older had testicular Leyd ig cell tumor. Testicular tissue sections from 27-month-old rats examined i mmunohistochemically showed strong positive staining for all 3 inhibin subu nits, in particular inhibin alpha and betaA subunits, in the tumor cells. P lasma concentrations of ir-inhibin began to rise significantly (P<.05) at 1 8 months of age. High bioactivity of inhibin was detected not only in testi cular extracts but also in peripheral plasma of aged rats. Thus, plasma con centrations of bioactive inhibin-A, but not inhibin-B, were significantly e levated with increasing age. The concentrations were significantly higher t han those in normal male (P<.01) or normal female (P<.05) rats. Plasma conc entrations of E-2 were significantly (P<.05) elevated only at 23-24 months of age. A marked reduction (P<.05 to .001) in plasma LH and FSH concentrati ons was observed at 18 months of age and older. Plasma concentrations of te stosterone were highest at 2 months of age and then decreased gradually and significantly (P<.05 to .001) afterward. Significant (P<.05 to .001) posit ive (testosterone vs LH) and negative (ir-inhibin vs FSH, ir-inhibin vs LH, and E2 vs FSH) correlations were observed. It is suggested that plasma inh ibin-A levels are elevated in male Tig:Wistar rats with Leydig cell tumor, and thus inhibin-A may be used as a specific marker of testicular Leydig ce ll tumors. The present results also suggest that the age-related decline in plasma gonadotropins and thus testosterone levels in Tig:Wistar rats may b e due to the development of tumors of the Leydig cells rather than to aging per se.