Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Curr Opin Pharmacol. 2011 Dec;11(6):670-5. doi: 10.1016/j.coph.2011.09.003. Epub 2011 Sep 29.
The second messenger, cAMP, is one of the most important regulatory signals for control of steroidogenesis. This review focuses on current knowledge about regulation of cyclic nucleotides by phosphodiesterases (PDEs) in steroidogenic tissues. The first PDE known to directly regulate steroidogenesis was PDE2, the cGMP-stimulated PDE. PDE2 mediates ANP/cGMP-induced decreases in aldosterone production. Recently, the PDE8 family has been shown to control steroidogenesis in two tissues. Specifically, PDE8A regulates testosterone production by itself and in concert with additional IBMX-sensitive PDEs. PDE8B modulates basal corticosterone synthesis via acute and chronic mechanisms. In addition to cAMP-dependent pathways, cGMP signaling also can promote steroidogenesis, and PDE5 modulates this process. Finally, PDE mutations may lead to several human diseases characterized by abnormal steroid levels.
第二信使 cAMP 是甾体激素生物合成调控的最重要的调节信号之一。这篇综述主要关注磷酸二酯酶（PDEs）对甾体生成组织中环核苷酸的调节的最新知识。已知的第一个直接调节甾体激素生物合成的 PDE 是 PDE2，即 cGMP 刺激的 PDE。PDE2 介导 ANP/cGMP 诱导的醛固酮产生减少。最近，PDE8 家族已被证明在两种组织中控制甾体激素生物合成。具体而言，PDE8A 通过自身和与其他 IBMX 敏感的 PDE 协同作用来调节睾酮的产生。PDE8B 通过急性和慢性机制调节基础皮质酮的合成。除了 cAMP 依赖性途径外，cGMP 信号也可以促进甾体激素生物合成，PDE5 调节此过程。最后，PDE 突变可能导致几种以异常甾体水平为特征的人类疾病。
