Gonadotropin subunit transcriptional responses to calcium signals in the rat: Evidence for regulation by pulse frequency

Alterations in the frequency of calcium influx signals to rat pituitary cel ls can regulate the expression of gonadotropin subunit mRNAs in a different ial manner, producing effects that are similar to those previously found fo r GnRH. The present study was conducted to investigate whether this reflect s a transcriptional response to calcium pulse frequency, as determined by a lterations in primary transcript (PT) expression. Perifused rat pituitary c ells were given pulses of the calcium channel-activator Bay K 8644 (BK; wit h 10 mM KCl in the injectate) for 6 h. The response to alterations in pulse dose was examined by giving pulses of 1, 3, or 10 muM BK at 60-min interva ls. Maximal increases in LH beta and FSH beta PTs were obtained with the 3- muM BK pulse dose and with the 10-muM dose for alpha. To investigate the ef fect of calcium pulse frequency, 3-muM BK pulses were given at intervals of 15, 60, or 180 min. Alpha PT was selectively stimulated by 15-min pulses a nd LH beta by 15- and 60-min pulses of BK. In contrast, FSH beta PT was max imally stimulated by the slower, 180-min pulse interval. These findings rev eal that pulsatile increases in intracellular calcium stimulate alpha, LH b eta, and FSH beta transcription in a differential manner. Thus, intermitten t changes in intracellular calcium appear to be important in the transmissi on of GnRH pulse signals from the plasma membrane to the gene, and they may mediate the differential actions of pulse frequency on gonadotropin subuni t gene expression.