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

J Comp Neurol. 2006 May 10;496(2):252-68. doi: 10.1002/cne.20949.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoradiography / methods
  • Estrogens / pharmacology*
  • Female
  • Gene Expression / drug effects*
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • In Situ Hybridization / methods
  • Limbic System / drug effects*
  • Opioid Peptides / genetics
  • Opioid Peptides / metabolism*
  • Ovariectomy / methods
  • Progestins / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism*


  • Estrogens
  • Opioid Peptides
  • Progestins
  • RNA, Messenger
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor