This Article Full Text (PDF) References 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 Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Naftolin, F. Articles by Parducz, A. Search for Related Content PubMed PubMed Citation Articles by Naftolin, F. Articles by Garcia-Segura, L. M. Articles by Horvath, T. L. Articles by Zsarnovszky, A. Articles by Demir, N. Articles by Fadiel, A. Articles by Leranth, C. Articles by Vondracek-Klepper, S. Articles by Lewis, C. Articles by Chang, A. Articles by Parducz, A. Social Bookmarking                         What's this?

Estrogen-Induced Hypothalamic Synaptic Plasticity and Pituitary Sensitization in the Control of the Estrogen-Induced Gonadotrophin Surge

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, frederick.naftolin{at}med.nyu.edu

Luis Miguel Garcia-Segura, PhD

Instituto Cajal, CSIC, Madrid, Spain

Tamas L. Horvath, DVM, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Attila Zsarnovszky, DVM, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Necdet Demir, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, Department of Histology & Embryology, Medical Faculty, Akdeniz University, Antalya,Turkey

Ahmed Fadiel, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York

Csaba Leranth, MD, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Susanne Vondracek-Klepper, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Carole Lewis, PhD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Aimee Chang, MD

Reproductive Neuroscience Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Arpad Parducz, PhD

Institute of Biophysics. Szeged, Hungary

Proper gonadal function requires coordinated (feedback) interactions between the gonads, adenohypophysis, and brain: the gonads elaborate sex steroids (progestins, androgens, and estrogens) and proteins (inhibin-activin family) during gamete development. In both sexes, the brain-pituitary gonadotrophin-regulating interaction is coordinated by estradiol through its opposing actions on pituitary gonadotrophs (sensitization of the response to gonadotrophin-releasing hormone [GnRH]) versus hypothalamic neurons (inhibition of GnRH secretion). This dynamic tension between the gonadotrophs and the GnRH cells in the brain regulates the circulating gonadotrophins and is termed reciprocal/negative feedback. In females, reciprocal/negative feedback dominates 90% of the ovarian cycle. In a spectacular exception, the dynamic tension is broken during the surge of circulating estrogen that marks follicle and oocyte(s) maturation. The cause is an estradiol-induced disinhibition of the GnRH neurons that releases GnRH secretion to the highly sensitized pituitary gonadotrophs that in turn release the gonadotrophin surge (the estrogen-induced gonadotrophin surge [EIGS], also known as positive feedback). Studies during the past 4 decades have shown this disinhibition to result from estrogen-induced synaptic plasticity (EISP), including a reversible 50% loss in arcuate nucleus synapses. The disinhibited GnRH secretion occurs during maximal gonadotroph sensitization and results in the EIGS. Specific immunoneutralization of estradiol blocks the EISP and EIGS. The EISP is accompanied by increases in insulinlike growth factor 1, polysialylated neural cell adhesion molecule, and ezrin, 3 proteins that the authors believe are the links between estrogen-induced astroglial extension and the EISP that releases GnRH secretion at the moment of maximal sensitization of the pituitary gonadotrophs. The result is the paradoxical surge of gonadotrophins at the peak of ovarian estrogen secretion and the triggering of ovulation. This enhanced understanding of the mechanics of gonadotrophin control clarifies elements of the involved feedback loops and opens the way to a better understanding of the neurobiology of reproduction.

Key Words: Periventriculararea • luteinizinghormone • follicle-stimulating hormone • gonadotrophin feedback • hypothalamus • estradiol • synaptic plasticity • pituitary • GnRH

Reproductive Sciences, Vol. 14, No. 2, 101-116 (2007)
DOI: 10.1177/1933719107301059


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				O. Tan, A. Fadiel, A. Chang, N. Demir, R. Jeffrey, T. Horvath, L.-M. Garcia-Segura, and F. Naftolin Estrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge Endocrinology, June 1, 2009; 150(6): 2783 - 2790. [Abstract] [Full Text] [PDF]

				K. Guo, J. Mogen, S. Struzzi, and Y. Zhang Preadipocyte transplantation: an in vivo study of direct leptin signaling on adipocyte morphogenesis and cell size Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1339 - R1347. [Abstract] [Full Text] [PDF]

				Z. Zhao, C. Park, M. A. McDevitt, C. Glidewell-Kenney, P. Chambon, J. Weiss, J. L. Jameson, and J. E. Levine p21-Activated kinase mediates rapid estradiol-negative feedback actions in the reproductive axis PNAS, April 28, 2009; 106(17): 7221 - 7226. [Abstract] [Full Text] [PDF]

				F. Gaytan, M. Gaytan, J. M. Castellano, M. Romero, J. Roa, B. Aparicio, N. Garrido, J. E. Sanchez-Criado, R. P. Millar, A. Pellicer, et al. KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E520 - E531. [Abstract] [Full Text] [PDF]

				M. Kouzu-Fujita, Y. Mezaki, S. Sawatsubashi, T. Matsumoto, I. Yamaoka, T. Yano, Y. Taketani, H. Kitagawa, and S. Kato Coactivation of Estrogen Receptor {beta} by Gonadotropin-Induced Cofactor GIOT-4 Mol. Cell. Biol., January 1, 2009; 29(1): 83 - 92. [Abstract] [Full Text] [PDF]

				J. Roa, E. Vigo, J. M. Castellano, F. Gaytan, D. Garcia-Galiano, V. M. Navarro, E. Aguilar, F. A. Dijcks, A. G. H. Ederveen, L. Pinilla, et al. Follicle-Stimulating Hormone Responses to Kisspeptin in the Female Rat at the Preovulatory Period: Modulation by Estrogen and Progesterone Receptors Endocrinology, November 1, 2008; 149(11): 5783 - 5790. [Abstract] [Full Text] [PDF]

				J. Roa, E. Vigo, J. M. Castellano, F. Gaytan, V. M. Navarro, E. Aguilar, F. A. Dijcks, A. G. H. Ederveen, L. Pinilla, P. I. van Noort, et al. Opposite Roles of Estrogen Receptor (ER)-{alpha} and ER{beta} in the Modulation of Luteinizing Hormone Responses to Kisspeptin in the Female Rat: Implications for the Generation of the Preovulatory Surge Endocrinology, April 1, 2008; 149(4): 1627 - 1637. [Abstract] [Full Text] [PDF]