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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
, 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.
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 (5378%
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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