This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goodman, R. L. Articles by Lehman, M. N. Search for Related Content PubMed PubMed Citation Articles by Goodman, R. L. Articles by Lehman, M. N.

Evidence That Dynorphin Plays a Major Role in Mediating Progesterone Negative Feedback on Gonadotropin-Releasing Hormone Neurons in Sheep

Department of Physiology and Pharmacology (R.L.G., G.M.A., S.L.H., M.V., J.M.C.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229; and Department of Cell Biology, Neurobiology, and Anatomy (L.M.C., M.E.F., M.N.L.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521

Address all correspondence and requests for reprints to: Dr. Robert L. Goodman, Department of Physiology and Pharmacology, Health Sciences Center North, Medical Center Drive, Morgantown, West Virginia 26506-9229. E-mail: bgoodman{at}hsc.wvu.edu.

Endogenous opioid peptides (EOP) mediate progesterone-negative feedback in many species, but the specific EOP systems involved remain unresolved. We first addressed this question in sheep by determining the role of different EOP receptor subtypes in the medial basal hypothalamus (MBH) and preoptic area (POA). Local administration of EOP receptor antagonists to luteal phase ewes indicated that -, but not µ- or -, receptors mediate the inhibition of LH secretion in the MBH. In contrast, both - and µ-, but not -receptor, antagonists increased LH pulse frequency when placed in the POA. We next examined close appositions between dynorphin ( ligand) and ß-endorphin (µ ligand) containing varicosities and GnRH perikarya in luteal phase ewes using dual immunocytochemistry and light microscopy. Approximately 90% of MBH GnRH neurons had close associations by dynorphin-containing varicosities, but only 40–50% of GnRH perikarya elsewhere had such close associations. In contrast, the percentage of ß-endorphinergic varicosities close to GnRH neurons was similar among all regions. Electron microscopic analysis demonstrated both dynorphinergic synapses and ß-endorphinergic synapses onto GnRH perikarya. These and other data lead to the hypothesis that dynorphin neurons play a major role in progesterone-negative feedback in the ewe and that this inhibition may be exerted directly on GnRH perikarya within the MBH, whereas dynorphin and ß-endorphin input to GnRH neurons in the POA provide redundancy to this system or are involved in other actions of progesterone or estradiol in the control of the GnRH surge.

This article has been cited by other articles:

				J. T. Smith, L. M. Coolen, L. J. Kriegsfeld, I. P. Sari, M. R. Jaafarzadehshirazi, M. Maltby, K. Bateman, R. L. Goodman, A. J. Tilbrook, T. Ubuka, et al. Variation in Kisspeptin and RFamide-Related Peptide (RFRP) Expression and Terminal Connections to Gonadotropin-Releasing Hormone Neurons in the Brain: A Novel Medium for Seasonal Breeding in the Sheep Endocrinology, November 1, 2008; 149(11): 5770 - 5782. [Abstract] [Full Text] [PDF]

				A. L. Bogusz, S. L. Hardy, M. N. Lehman, J. M. Connors, S. M. Hileman, J. H. Sliwowska, H. J. Billings, C. J. McManus, M. Valent, S. R. Singh, et al. Evidence that {gamma}-Aminobutyric Acid Is Part of the Neural Circuit Mediating Estradiol Negative Feedback in Anestrous Ewes Endocrinology, June 1, 2008; 149(6): 2762 - 2772. [Abstract] [Full Text] [PDF]

				R. L. Goodman, M. N. Lehman, J. T. Smith, L. M. Coolen, C. V. R. de Oliveira, M. R. Jafarzadehshirazi, A. Pereira, J. Iqbal, A. Caraty, P. Ciofi, et al. Kisspeptin Neurons in the Arcuate Nucleus of the Ewe Express Both Dynorphin A and Neurokinin B Endocrinology, December 1, 2007; 148(12): 5752 - 5760. [Abstract] [Full Text] [PDF]

				H. M. Dungan, M. L. Gottsch, H. Zeng, A. Gragerov, J. E. Bergmann, D. K. Vassilatis, D. K. Clifton, and R. A. Steiner The Role of Kisspeptin GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone J. Neurosci., October 31, 2007; 27(44): 12088 - 12095. [Abstract] [Full Text] [PDF]

				C. D. Foradori, M. Amstalden, L. M. Coolen, S. R. Singh, C. J. McManus, R. J. Handa, R. L. Goodman, and M. N. Lehman Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System Endocrinology, October 1, 2007; 148(10): 4993 - 5001. [Abstract] [Full Text] [PDF]

				C. J McManus, M. Valent, S. L Hardy, and R. L Goodman Does nitric oxide act in the ventromedial preoptic area to mediate oestrogen negative feedback in the seasonally anoestrous ewe? Reproduction, July 1, 2007; 134(1): 137 - 145. [Abstract] [Full Text] [PDF]

				J. A. Taylor, M.-L. Goubillon, K. D. Broad, and J. E. Robinson Steroid Control of Gonadotropin-Releasing Hormone Secretion: Associated Changes in Pro-Opiomelanocortin and Preproenkephalin Messenger RNA Expression in the Ovine Hypothalamus Biol Reprod, March 1, 2007; 76(3): 524 - 531. [Abstract] [Full Text] [PDF]

				V. L. Adams, R. L. Goodman, A. K. Salm, L. M. Coolen, F. J. Karsch, and M. N. Lehman Morphological Plasticity in the Neural Circuitry Responsible for Seasonal Breeding in the Ewe Endocrinology, October 1, 2006; 147(10): 4843 - 4851. [Abstract] [Full Text] [PDF]

				C. D. Foradori, R. L. Goodman, V. L. Adams, M. Valent, and M. N. Lehman Progesterone Increases Dynorphin A Concentrations in Cerebrospinal Fluid and Preprodynorphin Messenger Ribonucleic Acid Levels in a Subset of Dynorphin Neurons in the Sheep Endocrinology, April 1, 2005; 146(4): 1835 - 1842. [Abstract] [Full Text] [PDF]