Abstract
Aim:
To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-like 1 receptor (ORL1 receptor) in the estrus cycle of female rats.
Method:
Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphe1]Nociceptin(1-13)NH2, that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohistochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat.
Results:
Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreatment with 20 nmol NC13. The OFQ mRNA level in the POA on proestrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreactive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and estrus (P<0.05).
Conclusion:
The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on proestrus suggests that it might play a negative modulatory role in the estrus cycle.
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References
Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsem RA, Bunzow JR, et al. Orphanin FQ: a neuropeptide that activates an opioid-like G protein-coupled receptor. Science 1995; 270: 792–4.
Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, et al. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 1995; 377: 532–5.
Calo G, Guerrini R, Rizzi A, Salvadori S, Regoli D . Pharmacology of nociceptin and its receptor: a novel therapeutic target. Br J Pharmacol 2000; 129: 1261–83.
Wanger EJ, Ronnekleiv OK, Grandy DK, Kelly MJ . The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance. Neuroendocrinology 1998; 67: 73–82.
Bryant W, Janik J, Baumann M, Callahan P . Orphanin FQ stimulates prolactin and growth hormone secretion in male and female rats. Brain Res 1998; 807: 228–33.
Chesterfield M, Janik J, Murphree E, Lynn C, Schmidt E, Callahan P . Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats. Endocrinology 2006; 147: 5087–93.
Dhandapani KM, Brann DW . Orphanin FQ inhibits GnRH secretion from rat hypothalamic fragments but not GT1-7 neurons. Neuroreport 2002; 13: 1247–9.
An XF, Chen HP, Ma SL, Feng Y, Hao JW, Chen BY . Involvement of nociceptin/orphanin FQ in release of hypothalamic GnRH mediated by ORL1 receptor in ovariectomized rats. Acta Pharmacol Sin 2005; 26: 1039–44.
Herbison AE . Multimodal influence of estrogen upon gonadotropin releasing hormone. Endocr Rev 1998; 19: 302–30.
Smith MJ, Jennes L . Neural signals that regulate GnRH neurones directly during the oestrous cycle. Reproduction 2001; 122: 1–10.
Kalra SP . Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone-releasing hormone discharge. Endocr Rev 1993; 14: 507–37.
Goodman RL, Gibson M, Skinner DC, Lehman MN . Neuroendocrine control of pulsatile GnRH secretion during the ovarian cycle: evidence from the ewe. Reprod Suppl 2002; 59: 41–56.
Neal CR, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Watson SJ . Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system. J Comp Neurol 1999; 406: 503–47.
Sharma P, Kaur G, Bhardwaj SK, Kaur G . Role of opioidergic and monoaminergic neurotransmission in the GnRH release mechanism of EBP-primed OVX rats. Brain Res Bull 1998; 47: 81–6.
Kaur G, Kaur G . Role of cholinergic and GABAergic neurotransmission in the opioids-mediated GnRH release mechanism of EBP-primed OVX rats. Mol Cell Biochem 2001; 219: 13–9.
Paxinos G, Watson C . The rat brain in stereotaxic coordinates, 4th ed. New York: Academic Press; 1998.
Lamar CA, Bhat GK, Mahesh VB, Brann DW . Evidence that neuronal oxide synthase but not heme oxygenase increases in the hypothalamus on proestrous afternoon. Neuroendocrinology 1999; 70: 360–7.
Briscini L, Corradini L, Ongini E, Bertorelli R . Up-regulation of ORL1 receptors in spinal tissue of allodynic rats after sciatic nerve injury. Eur J Pharmacol 2002; 447: 59–65.
Pau KY, Spies HG . Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. Chin J Physiol 1997; 40: 181–96.
Funabashi T, Mitsushima D, Nakamura TJ, Uemura T, Hirahara F, Shinohara K, et al. Gonadotropin-releasing hormone (GnRH) surge generator in female rats. Prog Brain Res 2002; 141: 165–73.
Neal CR, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Akil H, et al. Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: Comparison of ORL1 receptor mRNA expression with 125I-[14Tyr]-orphanin FQ binding. J Comp Neurol 1999; 412: 563–605.
Smith MJ, Jennes L . Neural signals that regulate GnRH neurons directly during the oestrous cycle. Reproduction 2001; 122: 1–10.
Isgor C, Shieh KR, Akil H, Watson SJ . Colocalization of estrogen beta-receptor messenger RNA with orphanin FQ, vasopressin and oxytocin in the rat hypothalamic paraventricular and supraoptic nuclei. Anat Embryol (Berl) 2003; 206: 461–9.
Sinchak K, Romeo HE, Micevych PE . Site-specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociception opioid receptor mRNA expression in the female rat limbic hypothalamic system. J Comp Neurol 2006; 496: 252–68.
Flores CA, Shughrue P, Petersen SL, Mokha SS . Sex-related differences in the distribution of opioid receptor-like 1 receptor mRNA and colocalization with estrogen receptor mRNA in neurons of the spinal trigeminal nucleus caudalis in the rat. Neuroscience 2003; 118: 769–78.
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An, Xf., Yu, Jy., Feng, Y. et al. Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats. Acta Pharmacol Sin 28, 1189–1197 (2007). https://doi.org/10.1111/j.1745-7254.2007.00587.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00587.x