Mechanisms of testosterone action on the male pelvic autonomic nervous system: the role of estrogens

这个项目的目的是了解循环激素睾酮如何影响成年男性的自主神经系统。我们特别感兴趣的是这种激素对泌尿生殖器官的神经供应的影响，即。下尿路和生殖器官。我们已经发现，盆腔自主神经系统的许多不同部分都对雄激素敏感，如果激素水平显著下降，那么神经元的许多特性就会发生变化。这可能会对阴茎勃起、前列腺分泌和精液推进等反射产生负面影响。我们最近的实验表明，这些行为中的许多可能是由睾酮以一种不涉及其受体分子（雄激素受体）的典型激活的方式起作用引起的，我们认为它很可能首先被一些盆腔自主神经元转化为雌二醇。我们最近发现，雌二醇对这些神经元中的信号级联具有强有力的作用，并且许多神经元产生雌激素受体。也有可能是睾酮导致器官释放生长因子，而这些生长因子导致神经供应的变化。我们将研究这两种可能性。这项研究的结果将有助于了解盆腔自主神经反射如何受到内分泌失调、衰老和各种作用于内分泌系统的药物的影响。我们的研究结果也可能有助于设计作用于内分泌系统但对神经系统副作用较少的药物。

The aim of this project is to understand how the circulating hormone, testosterone, affects the autonomic nervous system in adult males. We are particularly interested in the effects this hormone has on the nerve supply of the urogenital organs, ie. the lower urinary tract and reproductive organs. We have already found that many different parts of this pelvic autonomic nervous system are androgen-sensitive, and if the levels of hormones drop significantly, then many properties of the neurons change. This is likely to impact negatively on reflexes like penile erection, prostate secretion and propulsion of seminal fluid. Our recent experiments suggest that many of these actions may be caused by testosterone acting in a way that does not involve the typical activation of its receptor molecule (the androgen receptor) and we think it is very likely that it is first converted by some pelvic autonomic neurons into estradiol. We have recently shown that estradiol has potent actions on signalling cascades in these neurons, and that many of the neurons make estrogen receptors. It is also possible that testosterone causes the release of growth factors from the organs, and these growth factors cause changes in their nerve supply. We will investigate both of these possibilities. The outcomes of this study will be relevant for understanding how pelvic autonomic reflexes are affected by endocrine disorders, ageing and various drugs that act on the endocrine system. Our results may also be useful for designing drugs that act on the endocrine system but with less side-effects on the nervous system.