Effects of aging and melatonin administration on gonadotropin-releasing hormones (GnRH) gene expression in the male and female rat.

It is well documented that in the rat of both sexes aging is associated with a decline in reproductive functions. We have recently shown that melatonin exerts a positive influence on GnRH gene expression in the adult male rats. In order to evaluate the effect of aging as well as melatonin on GnRH mRNA levels, we have studied the effect of 2.5-day administration of melatonin to young (50-55 day of age) and aged (18 month of age) rats of both sexes. In the young males melatonin induced a 11% increase in the hybridization signal. In the aged males, the GnRH mRNA levels were 13% lower than those observed in the young animals. Melatonin administration to aged animals completely restored GnRH mRNA levels when compared to those observed in the young untreated male rats. In contrast, melatonin did not modify the hybridization signal in young female rats, while aging induced a 20% decrease in mRNA levels. Melatonin administration to aged female induced a 18% increase in GnRH mRNA levels, thus completely reversing the influence of aging. These results indicate that the decrease in GnRH gene expression which is likely involved in the decline of reproductive functions in aging can be totally reversed by a short term administration of melatonin, then suggesting that the pineal hormone may be involved in the decrease of GnRH neuronal activity during aging.