Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone

Estrogen has been shown to increase proenkephalin (PE) mRNA levels in neurons of the ventrolateral aspect of the ventromedial hypothalamic nucleus (VL-VM). In this series of experiments, we examined the temporal qualities of this induction by determining both the latency of the estrogen-induced elevation in PE mRNA levels and the rate at which the message levels decline following removal of estrogen. In addition we have examined the effects of progesterone on PE gene expression in the VL-VM of estrogen-primed rats. The latency of the estrogen-induced elevation in PE mRNA levels was found to be relatively short: PE mRNA levels were increased 2-fold within 1 h of estrogen replacement. Following estrogen removal the levels of PE mRNA declined rapidly. Progesterone treatment attenuated this decline, prolonging the estrogen-induced elevation of PE mRNA levels. These results suggest that estrogen rapidly increases PE mRNA levels through a mechanism that probably involves alterations in both the rate of appearance and the rate of degradation of the message. Together, the short latency of the estrogen-induced elevation and the rapid rate of decay following estrogen removal indicate that PE gene expression is highly sensitive to fluctuating estrogen levels. The effect of progesterone suggests that this enkephalinergic system may be regulated by both estrogen and progesterone during the estrous cycle.