This Article Full Text Full Text (PDF) Supplemental Data 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 Roepke, T. A. Articles by Rønnekleiv, O. K. Search for Related Content PubMed PubMed Citation Articles by Roepke, T. A. Articles by Rønnekleiv, O. K.

Estrogen Regulation of Genes Important for K⁺ Channel Signaling in the Arcuate Nucleus

Departments of Physiology and Pharmacology (T.A.R., A.M., M.A.B., M.J.K., O.K.R.) and Anesthesiology and Perioperative Medicine (O.K.R.), Division of Neuroscience (M.A.B., O.K.R.), Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Oline K. Rønnekleiv or Martin J. Kelly, Department of Physiology and Pharmacology, Mail Code L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239. E-mail: ronnekle{at}ohsu.edu or kellym{at}ohsu.edu.

Estrogen affects the electrophysiological properties of a number of hypothalamic neurons by modulating K⁺ channels via rapid membrane actions and/or changes in gene expression. The interaction between these pathways (membrane vs. transcription) ultimately determines the effects of estrogen on hypothalamic functions. Using suppression subtractive hybridization, we produced a cDNA library of estrogen-regulated, brain-specific guinea pig genes, which included subunits from three prominent K⁺ channels (KCNQ5, Kir2.4, Kv4.1, and Kvß₁) and signaling molecules that impact channel function including phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), cAMP-dependent protein kinase (PKA), A-kinase anchor protein (AKAP), phospholipase C (PLC), and calmodulin. Based on these findings, we dissected the arcuate nucleus from ovariectomized guinea pigs treated with estradiol benzoate (EB) or vehicle and analyzed mRNA expression using quantitative real-time PCR. We found that EB significantly increased the expression of KCNQ5 and Kv4.1 and decreased expression of KCNQ3 and AKAP in the rostral arcuate. In the caudal arcuate, EB increased KCNQ5, Kir2.4, Kv4.1, calmodulin, PKC, PLCß₄, and PI3Kp55 expression and decreased Kvß₁. The effects of estrogen could be mediated by estrogen receptor-, which we found to be highly expressed in the guinea pig arcuate nucleus and, in particular, proopiomelanocortin neurons. In addition, single-cell RT-PCR analysis revealed that about 50% of proopiomelanocortin and neuropeptide Y neurons expressed KCNQ5, about 40% expressed Kir2.4, and about 60% expressed Kv4.1. Therefore, it is evident that the diverse effects of estrogen on arcuate neurons are mediated in part by regulation of K⁺ channel expression, which has the potential to affect profoundly neuronal excitability and homeostatic functions, especially when coupled with the rapid effects of estrogen on K⁺ channel function.

This article has been cited by other articles:

				T. A. Roepke, C. Xue, M. A. Bosch, T. S. Scanlan, M. J. Kelly, and O. K. Ronnekleiv Genes Associated with Membrane-Initiated Signaling of Estrogen and Energy Homeostasis Endocrinology, December 1, 2008; 149(12): 6113 - 6124. [Abstract] [Full Text] [PDF]

				S. M. Dupre, D. W. Burt, R. Talbot, A. Downing, D. Mouzaki, D. Waddington, B. Malpaux, J. R. E. Davis, G. A. Lincoln, and A. S. I. Loudon Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control Endocrinology, November 1, 2008; 149(11): 5527 - 5539. [Abstract] [Full Text] [PDF]