Gonadotropin subunit and gonadotropin-releasing hormone receptor gene expression are regulated by alterations in the frequency of calcium pulsatile signals.
Previously, we have shown that intermittent calcium (Ca2+) stimuli increase alpha, LHbeta, and FSHbeta messenger RNAs (mRNAs), and only LHbeta 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 microM; 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 LHbeta mRNAs were maximally stimulated by 16- or 60-min pulses (57% and 74% increases, respectively), with 180-min pulses being less effective. In contrast, FSHbeta 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.
Haisenleder
D J
DJ
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA. djh2q@virginia.edu
Yasin
M
M
Marshall
J C
JC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000235:genetics*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011966:Receptors, LHRH / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*
D002120:Calcium Channel Agonists; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002118:Calcium