Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, C/Jose Antonio Novais no. 2, Madrid, Spain.
Neurosci Biobehav Rev. 2011 Aug;35(8):1740-51. doi: 10.1016/j.neubiorev.2010.09.005. Epub 2010 Sep 30.
This review highlights the salient findings that have furthered our understanding of how sex differences are initiated during development and maintained throughout life. First we discuss how gonadal steroid hormones organize the framework for sex differences within critical periods of development-namely, during those exposures which occur in utero and post-partum, as well as those which occur during puberty. Given the extensive precedence of sex differences in cannabinoid-regulated biology, we then focus on the disparities within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB(1) receptors is regulated throughout development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse, followed by the organizational and activational roles of gonadal steroids in establishing and maintaining the sex dependence in the biological actions of cannabinoids. Finally, we discuss ways to utilize this knowledge to strategically target critical developmental windows of vulnerability/susceptibility and thereby implement more effective therapeutic interventions for afflictions that may be more prevalent in one sex vs. the other.
这篇综述强调了一些显著的发现，这些发现进一步加深了我们对性别的差异是如何在发育过程中产生并在整个生命周期中维持的理解。首先，我们讨论了性腺类固醇激素如何在发育的关键时期为性别差异组织框架——即在胎儿期和产后期间以及青春期期间发生的那些暴露期间。鉴于大麻素调节生物学中存在广泛的性别差异，我们接下来关注内源性大麻素系统内的差异，以及观察到的外源性大麻素的差异。我们从大麻素 CB(1)受体的表达在整个发育过程中是如何被调节开始。接下来讨论了青春期大麻素暴露导致的病理后果的差异易感性。接下来我们讨论大麻素和其他滥用药物之间相互作用的性别差异，然后讨论性腺类固醇在建立和维持大麻素生物学作用的性别依赖性中的组织和激活作用。最后，我们讨论了如何利用这些知识有策略地针对脆弱性/易感性的关键发育窗口期，从而为那些在某个性别中比另一个性别更为普遍的疾病实施更有效的治疗干预措施。
