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, LH beta, and FSH beta messenger RNAs (mRNAs), and only LH beta 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 mu M; 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 LH beta mRNAs were maximally stimulated by 16- or 60-min pulses (57% and 74% increases, respectively), with 180-min pulses being less effective. In contrast, FSH beta 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% us. 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.