Hawes B E, Barnes S, Conn P M
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242-1109.
Endocrinology. 1993 May;132(5):2124-30. doi: 10.1210/endo.132.5.8386608.
A growing body of evidence suggests a role for guanyl nucleotide binding proteins (G proteins) in GnRH action. G protein activation provokes LH release, inositol phosphate (IP) production, decreased gonadotrope responsiveness to GnRH, increased gonadotrope responsiveness to the calcium ionophore A23187, and decreased GnRH receptor binding. The specific G proteins involved in these actions, however, are not known. This study uses pertussis toxin (PTX) and cholera toxin (CTX), which affect the activity of a number of G proteins by ADP ribosylation of a Cys or an Arg residue, respectively, of the alpha-subunit. Although not an effective LH secretagogue in itself, CTX enhanced GnRH-, NaF-, and A23187-stimulated LH release after an 18-h pretreatment period. CTX pretreatment did not affect GnRH- or NaF-stimulated IP production. Conversely, 18 h pretreatment with PTX reduced GnRH- and NaF-provoked IP production compared to control values, but did not affect LH release. In addition, pretreatment with either CTX, PTX, or Bt2cAMP provoked a decrease in GnRH receptor binding compared to control. The results of this study suggest that: 1) GnRH stimulates IP production, but not LH release, through a PTX-sensitive G protein; 2) A distinct CTX-sensitive G protein appears to provoke gonadotrope sensitization by stimulating an increase in intracellular cAMP levels; and 3) there appears to be a distinct G protein, insensitive to PTX and CTX, capable of mediating LH release independent of IP production and cAMP.
越来越多的证据表明鸟苷酸结合蛋白（G蛋白）在促性腺激素释放激素（GnRH）作用中发挥作用。G蛋白激活会引发促黄体生成素（LH）释放、肌醇磷酸（IP）生成、促性腺激素细胞对GnRH的反应性降低、促性腺激素细胞对钙离子载体A23187的反应性增加以及GnRH受体结合减少。然而，参与这些作用的具体G蛋白尚不清楚。本研究使用百日咳毒素（PTX）和霍乱毒素（CTX），它们分别通过对α亚基的半胱氨酸或精氨酸残基进行ADP核糖基化来影响多种G蛋白的活性。尽管CTX本身不是一种有效的LH促分泌剂，但在18小时预处理期后，它增强了GnRH、氟化钠（NaF）和A23187刺激的LH释放。CTX预处理不影响GnRH或NaF刺激的IP生成。相反，与对照值相比，PTX预处理18小时可降低GnRH和NaF引发的IP生成，但不影响LH释放。此外，与对照相比，用CTX、PTX或双丁酰环磷腺苷（Bt2cAMP）预处理会导致GnRH受体结合减少。本研究结果表明：1）GnRH通过一种对PTX敏感的G蛋白刺激IP生成，但不刺激LH释放；2）一种独特的对CTX敏感的G蛋白似乎通过刺激细胞内cAMP水平升高来引发促性腺激素细胞致敏；3）似乎存在一种对PTX和CTX不敏感的独特G蛋白，能够独立于IP生成和cAMP介导LH释放。
