The present study analyzed changes in the expression of RFamide-related peptide-3 (RFRP-3; a mammalian ortholog of avian gonadotropin-inhibitory hormone), in the brain and correlated it with testicular activity of mice of different age groups (day-old, 1-, 3-, 5-, 7-, 9-, 11-, 13-week and 1.5-year-old). Testicular activity after a progressive increase up to 13-week of age declined in the old mice. On the other hand, while immunoreactive (ir) RFRP-3 neurons were not seen in the day-old mice, few appeared in 1-week-old mice, their number and size increased drastically at 3-week of age. This condition remained unaltered until 7-week of age followed by a progressive decline up to the age of 13-week and thereafter increased again in the old age. The present findings indicate that hyperactivity of the ir-RFRP-3 neurons of dorsomedial nucleus of hypothalamus (DMH) observed in prepubertal mice declines in reproductively active mice and increases again in the old mice having declined reproductive performance. It is concluded that aging mice exhibits inverse correlation of RFRP-3 neurons and gonadal activity suggesting that function of RFRP-3 is not initiated until 1-week of age and thereafter it could participate in the regulation of gonadal development.
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