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Endocrinology Vol. 138, No. 12 5227-5230
Copyright © 1997 by The Endocrine Society


ARTICLES

Gonadotropin Subunit and Gonadotropin-Releasing Hormone Receptor Gene Expression Are Regulated by Alterations in the Frequency of Calcium Pulsatile Signals1

D. J. Haisenleder, M. Yasin and J. C. Marshall

Division of Endocrinology, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. D. J. Haisenleder, Division of Endocrinology, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908. E-mail: djh2q{at}virginia.edu

Previously, we have shown that intermittent calcium (Ca2+) stimuli increase {alpha}, LHß, and FSHß messenger RNAs (mRNAs), and only LHß mRNA was increased by continuous Ca2+. As gonadotropin subunit and GnRH receptor (GnRH-R) mRNAs are differentially regulated by alterations in GnRH pulse interval, we aimed to determine whether changes in the frequency of Ca2+ signals play a role in this effect. Cultured adult female rat pituitary cells in perifusion were given pulses of the Ca2+ channel activator BayK 8644 (10 µM; with 10 mM KCl in the injectate), at intervals of 16, 60, or 180 min for 24 h (vehicle pulses or 100 pM GnRH to controls). Pulsatile Ca2+ influx stimulated a rise in all mRNAs examined (P < 0.05 vs. vehicle controls); however, optimal pulse intervals differed. {alpha} and LHß mRNAs were maximally stimulated by 16- or 60-min pulses (57% and 74% increases, respectively), with 180-min pulses being less effective. In contrast, FSHß and GnRH-R mRNAs were selectively stimulated by 180-min pulses (51% and 41% increases, respectively). Pulsatile GnRH produced similar increases in GnRH-R and subunit mRNAs (53–78% vs. controls). These results reveal that alterations in the frequency of Ca2+ signals can regulate gonadotrope gene expression in a differential manner, producing effects similar to previous findings for GnRH. Thus, intermittent increases in intracellular Ca2+ may be an important step in the transmission of GnRH pulse signals from the plasma membrane to the gene.




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