Tsujii T, Winters S J
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pennsylvania 15213-2582, USA.
Life Sci. 1995 Feb 17;56(13):1103-11. doi: 10.1016/0024-3205(95)00047-a.
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.
研究了间歇性给予垂体腺苷酸环化酶激活多肽（PACAP）对7周龄完整和去势大鼠垂体前叶细胞促性腺激素分泌及亚基mRNA水平的影响。细胞用2.5 nM促性腺激素释放激素（GnRH）或10 nM PACAP的每小时脉冲进行9小时的灌流，或仅用培养基灌流。脉冲式PACAP引发了促黄体生成素（LH）、促卵泡生成素（FSH）和α-亚基的分泌，但效果远不如GnRH。尽管在整个实验过程中脉冲间期分泌逐渐增加，但随着PACAP重复脉冲，反应性下降。与完整大鼠相比，PACAP对去势大鼠垂体细胞释放LH的刺激作用稍强。在灌流结束时，提取去势大鼠的垂体RNA以测量促性腺激素亚基mRNA水平。脉冲式PACAP刺激α-亚基和LHβ mRNA水平，但不影响FSHβ mRNA。相比之下，持续给予PACAP增加α-亚基mRNA水平，但抑制FSHβ mRNA而不影响LHβ mRNA。我们得出结论，单独给予时，脉冲式PACAP对促性腺激素分泌的刺激作用相对较弱，并且与持续给予PACAP相比，其对促性腺激素亚基基因表达的调节方式有很大不同。我们认为，体内PACAP的分泌模式可能是促性腺激素亚基基因差异表达的一个决定因素。
