DOES AGE-ASSOCIATED REDUCED LEYDIG-CELL TESTOSTERONE PRODUCTION IN BROWN-NORWAY RATS RESULT FROM UNDER-STIMULATION BY LUTEINIZING-HORMONE

Previous studies have shown that reductions in Leydig cell testosteron e production occur with aging in the Brown Norway rat. The recent obse rvation that changes in luteinizing hormone (LH) pulse interval and am plitude also occur with aging suggests the possibility that age-relate d reduced Leydig cell steroidogenesis might be related to changes in L H. We reasoned that, if this is the case, exogenously administered LH should restore testosterone production by aged rat Leydig cells to the higher levels produced by Leydig cells of young rats. To test this hy pothesis, young (4-month-old) and aged (21-month-old) rats received te stosterone- and estradiol-containing Silastic implants designed to sup press LH and, thus, endogenous Leydig cell testosterone production. At the same time, the rats received miniosmotic pumps programmed to deli ver pulsatile ovine LH at a predetermined daily dose. In some experime nts, treatment effects were determined by measuring testosterone produ ction by testes perfused in vitro with maximally stimulating ovine LH. In others, Leydig cells were isolated by centrifugal elutriation and Percoll density gradient centrifugation, and their in vitro ability to produce testosterone in response to maximally stimulating LH was dete rmined. Testes or isolated Leydig cells from untreated young rats prod uced about twice as much testosterone as that produced by Leydig cells from aged rats. The administration of testosterone- and estradiol-fil led implants for 5 days reduced testosterone production significantly at both ages. In young rats administered 24 mu g LH/day for 5 days, al ong with the implants, testosterone production was maintained at the h igh level of the young controls. Comparable treatment of aged rats res ulted in testosterone production only at the low level of the aged con trols. Indeed, even with higher LH doses (36 mu g/day), testosterone p roduction by the aged rat Leydig cells did not rise above the aged-con trol level. The inability of exogenously administered LH to increase t estosterone production by testes and Leydig cells of aged rats suggest s that Leydig cell steroidogenic deficits in the aged Brown Norway rat are unlikely to be the result of age-related changes in LH.