Site-specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system.

The distributions of orphanin FQ (OFQ/N; also known as nociceptin) and its cognate receptor, opioid receptor-like receptor-1 (NOP), overlap steroid-responsive regions throughout reproductive circuits of the limbic system and hypothalamus. For example, in the ventromedial nucleus of the hypothalamus (VMH), OFQ/N facilitates lordosis in female rats through estrogen and progesterone regulation of nociceptin activity. We studied estrogen and progesterone regulation of OFQ/N and NOP mRNA expression in limbic-hypothalamic reproductive circuits. Ovariectomized rats were treated with 17beta-estradiol-benzoate (2 microg) and 26 hours later with oil or progesterone (500 microg) and were killed 30 hours after initial treatment. Alternate brain sections were processed for OFQ/N or NOP mRNA in situ hybridization. High levels of hybridization for NOP and OFQ/N and overlapping distributions were observed throughout the limbic hypothalamic reproductive circuits; however, in VMH, only NOP expression was observed. Estrogen treatment increased NOP mRNA expression in anteroventral periventricular nucleus (AVPV), median preoptic nucleus, and VMH. Subsequent progesterone treatment did not alter estrogen-induced expression of NOP mRNA in VMH or median preoptic nucleus but reduced expression in the AVPV. OFQ/N mRNA levels were also regulated by steroids. In the caudal part of the posterodorsal medial amygdala, estrogen increased OFQ/N mRNA levels, and progesterone did not alter this increase, whereas, in the medial part of the medial preoptic nucleus, estrogen and progesterone were needed to increase OFQ/N mRNA levels. Steroid regulation of OFQ/N and NOP in the medial preoptic nucleus and VMH is consistent with emerging data indicating that this opioid system regulates female reproduction.