Orphanin FQ: evidence for a role in the control of the reproductive neuroendocrine system.

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg(14), Lys(15)] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.

[1]  E. Murphree,et al.  Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats. , 2006, Endocrinology.

[2]  R. Goodman,et al.  Colocalisation of Dynorphin A and Neurokinin B Immunoreactivity in the Arcuate Nucleus and Median Eminence of the Sheep , 2006, Journal of neuroendocrinology.

[3]  P. Micevych,et al.  Site‐specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system , 2006, The Journal of comparative neurology.

[4]  I. Clarke,et al.  Progesterone-Receptive Dopaminergic and Neuropeptide Y Neurons Project from the Arcuate Nucleus to Gonadotropin-Releasing Hormone-Rich Regions of the Ovine Preoptic Area , 2006, Neuroendocrinology.

[5]  Hai Chen,et al.  Involvement of nociceptin/orphanin FQ in release of hypothalamic GnRH mediated by ORL1 receptor in ovariectomized rats , 2005, Acta Pharmacologica Sinica.

[6]  I. Clarke,et al.  Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area , 2005, Neuroendocrinology.

[7]  L. Coolen,et al.  Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep. , 2004, Endocrinology.

[8]  P. Olszewski,et al.  Printed in U.S.A. Copyright © 2004 by The Endocrine Society doi: 10.1210/en.2004-0016 Minireview: Characterization of Influence of Central Nociceptin/Orphanin FQ on Consummatory Behavior , 2022 .

[9]  M. Heinricher Orphanin FQ/nociceptin: from neural circuitry to behavior. , 2003, Life sciences.

[10]  S. Meis Nociceptin/Orphanin FQ: Actions within the Brain , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[11]  M. Hoversten,et al.  Nociceptin/Orphanin FQ Content is Decreased in Forebrain Neurones During Acute Stress , 2003, Journal of neuroendocrinology.

[12]  J. Costentin,et al.  Nociceptin/orphanin FQ and related peptides reduce the increase in plasma corticosterone elicited in mice by an intracerebroventricular injection. , 2002, Life sciences.

[13]  H. Akil,et al.  Expression of orphanin FQ and the opioid receptor-like (ORL1) receptor in the developing human and rat brain , 2002, Journal of Chemical Neuroanatomy.

[14]  L. Dufourny,et al.  Progesterone Receptor, Estrogen Receptor α, and the Type II Glucocorticoid Receptor Are Coexpressed in the Same Neurons of the Ovine Preoptic Area and Arcuate Nucleus: A Triple Immunolabeling Study1 , 2002, Biology of reproduction.

[15]  L. Coolen,et al.  Colocalization of progesterone receptors in parvicellular dynorphin neurons of the ovine preoptic area and hypothalamus. , 2002, Endocrinology.

[16]  D. Brann,et al.  Orphanin FQ inhibits GnRH secretion from rat hypothalamic fragments but not GT1-7 neurons , 2002, Neuroreport.

[17]  D. Rapetti,et al.  Endocrine effects of centrally injected nociceptin in the rat , 2002, Brain Research.

[18]  O. Civelli,et al.  The orphanin FQ/nociceptin knockout mouse: A behavioral model for stress responses , 2002, Neuropeptides.

[19]  R. Goodman,et al.  Oestradiol Microimplants in the Ventromedial Preoptic Area Inhibit Secretion of Luteinizing Hormone via Dopamine Neurones in Anoestrous Ewes , 2001, Journal of neuroendocrinology.

[20]  T. A. Richter,et al.  Role of endogenous opioid peptides in mediating progesterone-induced disruption of the activation and transmission stages of the GnRH surge induction process. , 2001, Endocrinology.

[21]  G. Pasternak,et al.  The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family. , 2001, Pharmacological reviews.

[22]  A. Herbison,et al.  Identification of neurokinin B-expressing neurons as an highly estrogen-receptive, sexually dimorphic cell group in the ovine arcuate nucleus. , 2000, Endocrinology.

[23]  D. Kapusta Neurohumoral effects of orphanin FQ/nociceptin: relevance to cardiovascular and renal function , 2000, Peptides.

[24]  O. Civelli,et al.  The orphanin FQ/nociceptin gene: structure, tissue distribution of expression and functional implications obtained from knockout mice , 2000, Peptides.

[25]  H. Akil,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 , 1999, The Journal of comparative neurology.

[26]  S. Watson,et al.  Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat , 1999, The Journal of comparative neurology.

[27]  R. G. Allen,et al.  Orphanin-FQ/Nociceptin (OFQ/N) Modulates the Activity of Suprachiasmatic Nucleus Neurons , 1999, The Journal of Neuroscience.

[28]  K. Mogi,et al.  Pulsatile release of luteinizing hormone-releasing hormone (LHRH) in cultured LHRH neurons derived from the embryonic olfactory placode of the rhesus monkey. , 1999, Endocrinology.

[29]  D. Grandy,et al.  The Peptide Orphanin FQ Inhibits β-Endorphin Neurons and Neurosecretory Cells in the Hypothalamic Arcuate Nucleus by Activating an Inwardly-Rectifying K+ Conductance , 1998, Neuroendocrinology.

[30]  P. Micevych,et al.  Orphanin FQ/nociceptin in the ventromedial nucleus facilitates lordosis in female rats , 1997, Neuroreport.

[31]  B Anton,et al.  Immunohistochemical localization of ORL‐1 in the central nervous system of the rat , 1996, The Journal of comparative neurology.

[32]  R. Goodman,et al.  Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe. , 1995, Endocrinology.

[33]  W. Wetsel,et al.  Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[34]  R. Heavens,et al.  Distribution and cellular localization of preproenkephalin mRNA in the ovine brain and pituitary. , 1992, Brain research. Molecular brain research.

[35]  S. Wiegand,et al.  Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology , 1986, Peptides.

[36]  M. Lehman,et al.  Immunocytochemical localization of luteinizing hormone‐releasing hormone (LHRH) pathways in the sheep brain during anestrus and the mid‐luteal phase of the estrous cycle , 1986, The Journal of comparative neurology.

[37]  R. Oriol,et al.  An improved mounting medium for immunofluorescence microscopy. , 1985, Archives of pathology & laboratory medicine.

[38]  J. Levine,et al.  Simultaneous measurement of luteinizing hormone-releasing hormone and luteinizing hormone release in unanesthetized, ovariectomized sheep. , 1982, Endocrinology.

[39]  R. Goodman,et al.  Pulsatile secretion of luteinizing hormone: differential suppression by ovarian steroids. , 1980, Endocrinology.

[40]  M. Dubois,et al.  Immunocytochemistry of luteinizing hormone releasing hormone (LHRH) in the sheep hypothalamus during various reproductive stages , 1980, Cell and Tissue Research.

[41]  S. Douglas Distribution of Gonadotropin-Releasing Hormone in the Mouse Brain as Revealed by Immunohistochemistry , 1976 .

[42]  D. Naik,et al.  Immunoreactive LH-RH neurons in the hypothalamus identified by light and fluorescent microscopy , 2004, Cell and Tissue Research.

[43]  W. Dees,et al.  Immunohistochemical localization of gonadotropin-releasing hormone (GnRH) in the brain and infundibulum of the sheep , 2004, Cell and Tissue Research.

[44]  G. Calo’,et al.  [Arg14,Lys15]Nociceptin, a Highly Potent Agonist of the Nociceptin/Orphanin FQ Receptor: in Vitro and in Vivo Studies , 2002 .

[45]  A. R. Midgley,et al.  Dynamics of gonadotropin-releasing hormone release during a pulse. , 1992, Endocrinology.

[46]  J. D. Neill,et al.  The Physiology of reproduction , 1988 .

[47]  M. Dubois,et al.  Immunocytochemistry of luteinizing hormone releasing hormone (LHRH) in the sheep hypothalamus during variuos reproductive stages: correlation with the gonadotropic hormones of the pituitary. , 1980, Cell and tissue research.

[48]  D. Gross Distribution of gonadotropin-releasing hormone in the mouse brain as revealed by immunohistochemistry. , 1976, Endocrinology.

[49]  S R M REYNOLDS,et al.  Physiology of reproduction. , 1948, Annual review of physiology.