McArdle C A, Counis R
Department of Medicine, University of Bristol, Dorothy Crowfoot Hodgkins Laboratories, Bristol, UK.
Trends Endocrinol Metab. 1996 Jul;7(5):168-75. doi: 10.1016/1043-2760(96)00051-3.
In order to respond appropriately to their environment, gonadotropes, like other cells, must integrate informational input from multiple ligands acting through multiple intracellular signaling pathways. In recent years, an increasing number of examples of functional interactions between the phosphoinositidase C (PIC) and adenylyl cyclase signaling pathways in gonadotropes have been described, and the discovery that these cells are targets for pituitary adenylyl cyclase activating peptide (PACAP) has provided a physiological context for earlier work on gonadotrope regulation by cAMP. It has become clear that gonadotropes possess multiple PIC-coupled receptor types, in addition to receptors activating adenylyl and guanylyl cyclases, so that the potential for both coincidence signaling and cross-talk in these cells is immense; examples of both are seen in the effects of PACAP and GnRH on Ca(2+) mobilization and adenylyl cyclase activation in alphaT3-1 cells. In these cells, GnRH, acting via PIC-coupled receptors, can dramatically inhibit adenylyl cyclase activated by PACAP, but can also alter cellular levels of protein kinase A subunits, providing a mechanism for coordinated regulation of both messenger and effector.
为了对其环境做出适当反应，促性腺激素细胞与其他细胞一样，必须整合来自通过多种细胞内信号通路起作用的多种配体的信息输入。近年来，促性腺激素细胞中磷酸肌醇酶C（PIC）和腺苷酸环化酶信号通路之间功能相互作用的例子越来越多，并且这些细胞是垂体腺苷酸环化酶激活肽（PACAP）的靶标的发现，为早期关于cAMP对促性腺激素细胞调节的研究提供了生理学背景。已经清楚的是，促性腺激素细胞除了具有激活腺苷酸环化酶和鸟苷酸环化酶的受体外，还拥有多种与PIC偶联的受体类型，因此这些细胞中同时信号传导和相互作用的潜力巨大；在PACAP和GnRH对αT3-1细胞中Ca(2+)动员和腺苷酸环化酶激活的影响中都可以看到这两种情况的例子。在这些细胞中，GnRH通过与PIC偶联的受体起作用，可以显著抑制PACAP激活的腺苷酸环化酶，但也可以改变蛋白激酶A亚基的细胞水平，为信使和效应器的协调调节提供了一种机制。
