GONADOTROPIN-RELEASING HORMONE-INDUCED SENSITIZATION OF CALCIUM-DEPENDENT EXOCYTOSIS IN PITUITARY GONADOTROPHS

被引:21
作者
JOBIN, RM [1 ]
TOMIC, M [1 ]
ZHENG, LX [1 ]
STOJILKOVIC, SS [1 ]
CATT, KJ [1 ]
机构
[1] NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA
关键词
D O I
10.1210/en.136.8.3398
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Agonist-induced increases in cytoplasmic calcium concentration ([Ca2+](i)) play a pivotal role in regulated exocytosis by promoting the fusion of secretory vesicles with the plasma membrane. In permeabilized and ATP-primed pituitary cells, increases in ambient [Ca2+](i) stimulated the release of LH from gonadotrophs with an EC(50) of 2-3 mu M. In contrast, the responses of intact gonadotrophs to agonist stimulation by GnRH were characterized by transient [Ca2+](i) elevations of up to 1.5 mu M, followed by a plateau of 300-400 nM. The sensitivity of the exocytotic response of permeabilized cells to [Ca2+](i) was significantly increased by GnRH, which reduced the EC(50) for [Ca2+](i) to the submicromolar concentration range. The stimulatory action of GnRH on LH release in permeabilized cells was not a consequence of intracellular Ca2+ release, but was associated with increased cytidine diphosphate diacylglycerol production Activation of protein kinase C by phorbol esters caused a similar increase in the Ca2+ sensitivity of LH release from permeabilized cells, and this effect was not additive to that of GnRH. Furthermore, the GnRH-induced increase in the sensitivity of the exocytotic response to Ca2+ was attenuated by inhibitors of protein kinase C. These findings indicate that although elevated [Ca2+](i) per se can promote LH release from permeabilized gonadotrophs, concomitant activation of protein kinase C is necessary to support exocytosis at the physiological [Ca2+](i) levels that prevail in GnRH-stimulated intact cells. Such sensitization of the Ca2+-dependent secretory mechanism by protein kinase C may be an important step in the agonist-induced release of LH from pituitary gonadotrophs.
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页码:3398 / 3405
页数:8
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