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Copper induces luteinizing hormone release and desensitization of pituitary gonadotropes
Authors:I Schvartz  E Hazum
Affiliation:2. Department of Endocrinology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China;1. Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil;2. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil;1. School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, 80639;2. Department of Chemistry and Biochemistry, University of Northern Colorado, Greeley, Colorado, 80639;3. Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
Abstract:Copper stimulated LH release from cultured rat pituitary cells in a dose-and time-dependent manner. After 4 h of incubation with 10 mu M Cu2+, LH release was stimulated by 3-fold. The release of LH stimulated by Cu2+ was Ca2+ dependent, thus excluding the possibility that the releasing activity of this divalent cation was due to a toxic effect on pituitary cells. The stimulatory action of Cu2+ is substantially mediated via the GnRH-receptors since Cu2+ inhibited 125I-Buserelin binding and since GnRH-antagonist blocked most of the Cu2+-stimulated LH release (80%). Both GnRH (1 microM) and Cu2+ (10 microM) induced desensitization of pituitary cells to a subsequent stimulation of either GnRH (0.5 nM) or Cu2+ (10 microM). However, in contrast to GnRH, Cu2+ did not induce down regulation of GnRH receptors. These findings suggest that the Cu2+ effects are mainly mediated through the GnRH receptors.
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