Effects of pulsatile pituitary adenylate cyclase activating polypeptide (PACAP) on gonadotropin secretion and subunit mRNA levels in perifused rat pituitary cells.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) administered intermittently on gonadotropin secretion and subunit mRNA levels in anterior pituitary cells from 7wk old intact and orchidectomized rats were studied. Cells were perifused for 9 h with hourly pulses of 2.5 nM GnRH or 10 nM PACAP, or with medium alone. Pulsatile PACAP initiated episodes of LH, FSH and alpha-subunit secretion, but was much less effective than GnRH. Responsiveness declined with repeated pulses of PACAP, although interpulse secretion increased gradually throughout the experiment. PACAP was a slightly more effective stimulator of LH release by pituitary cells from castrated than intact rats. At the completion of perifusion, pituitary RNA from castrated rats was extracted for measurement of gonadotropin subunit mRNA levels. Pulsatile PACAP stimulated alpha-subunit and LHbeta mRNA levels but did not affect FSHbeta mRNA. By contrast, continuous PACAP increased alpha-subunit mRNA levels, but suppressed FSHbeta mRNA without affecting LHbeta mRNA. We conclude that pulsatile PACAP is a relatively ineffective stimulator of gonadotropin secretion when administered alone, and regulates gonadotopin subunit gene expression quite differently than continuous PACAP. We propose that the mode of PACAP secretion in vivo may be a determinant of the differential expression of the gonadotropin subunit genes.