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

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Abstract
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 17β‐estradiol‐benzoate (2 μg) and 26 hours later with oil or progesterone (500 μg) 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. J. Comp. Neurol. 496:252–268, 2006.