Starling L, McIntosh R P, McIntosh J E
J Endocrinol. 1986 Oct;111(1):167-73. doi: 10.1677/joe.0.1110167.
The possible involvement of polyphosphoinositides in the stimulation of LH release was investigated. Dispersed sheep pituitary cells were incubated in test-tubes, or perifused in columns, with gonadotrophin-releasing hormone (GnRH) and Li+, or with a phorbol ester, and the amounts and patterns of LH release over time compared. Treatment with Li+ (10 mmol/l), which is known to increase levels of inositol phosphates in gonadotrophs, was shown to have effects only on the responses of desensitized cells, significantly decreasing the rate at which the cells desensitize (P less than 0.005) and decreasing the response to supramaximal levels of GnRH stimulus (P less than 0.01). It is suggested that these effects could be due to increased levels of inositol monophosphate, inositol bisphosphate or inositol 1,3,4-trisphosphate. Responses to single or repeated pulses of GnRH at 18-, 30- and 60-min intervals were not significantly altered. Phorbol 12-myristate 13-acetate (PMA), an activator of the calcium and phospholipid-dependent protein kinase (protein kinase C), was specifically active in releasing LH with a half-maximal stimulating dose of approximately 3 nmol/l. Phorbol 12,13-diacetate, which is structurally similar to PMA but does not activate protein kinase C, did not release LH, except at high levels in freshly dispersed cells. The timing of PMA-stimulated LH release was similar to that for GnRH-stimulated release, and PMA was able to release greater amounts of LH than could GnRH. This suggests that activation of protein kinase C is likely to be important in the GnRH-stimulated release of LH from gonadotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了多磷酸肌醇在促黄体生成素（LH）释放刺激中的可能作用。将分散的绵羊垂体细胞置于试管中孵育，或在柱中用促性腺激素释放激素（GnRH）和锂离子，或用佛波酯进行灌流，并比较LH随时间的释放量和模式。已知锂离子（10 mmol/l）可增加促性腺细胞中肌醇磷酸的水平，结果显示其仅对脱敏细胞的反应有影响，显著降低细胞脱敏速率（P<0.005），并降低对超最大剂量GnRH刺激的反应（P<0.01）。提示这些作用可能是由于单磷酸肌醇、二磷酸肌醇或1,3,4-三磷酸肌醇水平升高所致。在18分钟、30分钟和60分钟间隔对GnRH单次或重复脉冲的反应无明显改变。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），一种钙和磷脂依赖性蛋白激酶（蛋白激酶C）的激活剂，在释放LH方面具有特异性活性，半最大刺激剂量约为3 nmol/l。结构与PMA相似但不激活蛋白激酶C的佛波醇12,13-二乙酸酯，除在新鲜分散细胞中高浓度时外，不释放LH。PMA刺激LH释放的时间与GnRH刺激释放的时间相似，且PMA能够比GnRH释放更多的LH。这表明蛋白激酶C的激活可能在GnRH刺激促性腺细胞释放LH中起重要作用。（摘要截短于250字）
