Pereira Virgínia Mara, Costa Amilton P Raposo, Rosa-E-Silva Alzira Amelia Martins, Vieira Maria Aparecida Ribeiro, Reis Adelina Martha Dos
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Peptides. 2008 Nov;29(11):2024-32. doi: 10.1016/j.peptides.2008.08.005. Epub 2008 Aug 20.
Previous studies have established a stimulatory effect of natriuretic peptides (NP) on testosterone production in mouse Leydig cells as intense as that of LH. Chronic administration of ANP in mice, on the other side, reduced testosterone levels. So, the understanding of the role of ANP on testicular steroidogenesis has been impaired by discrepant findings. The aim of the present study was to clarify the physiological role of ANP in the rat testis steroidogenesis using a model that preserves the interactions between testis cells and a medium devoid of any circulating factors that could interfere with testosterone production. First, ANP was immunolocalized in the interstitial compartment of the rat testis, mainly in Leydig cells. We also determined the presence of ANP and both GC-A (guanylyl cyclase A) and C receptors by real-time PCR in testis. Perfusion in vitro of testis with ANP (1 and 3x10(-7)M) stimulated testosterone production in a time- and dose-dependent manner. On the other side, testosterone secretion induced by LH was blunted by ANP. Similar effect was obtained using the specific C receptor ligand, cANF, indicating the involvement of C receptor in such response. In conclusion, ANP stimulated testosterone production in the rat testis perfused in vitro but decreased testosterone production LH-induced, effect that seems to involve C receptor. To this extent, our results suggest the existence of a local and complex peptidergic system in the rat testis, involving ANP and its receptors that could importantly modulate the androgen biosynthesis.
先前的研究已经证实，利钠肽（NP）对小鼠睾丸间质细胞睾酮生成具有刺激作用，其强度与促黄体生成素（LH）相当。另一方面，在小鼠中慢性给予心房钠尿肽（ANP）会降低睾酮水平。因此，这些相互矛盾的研究结果妨碍了人们对ANP在睾丸类固醇生成中作用的理解。本研究的目的是使用一种能够保留睾丸细胞与不含任何可能干扰睾酮生成的循环因子的培养基之间相互作用的模型，来阐明ANP在大鼠睾丸类固醇生成中的生理作用。首先，通过免疫定位发现ANP主要存在于大鼠睾丸的间质区，主要在睾丸间质细胞中。我们还通过实时PCR检测了睾丸中ANP以及鸟苷酸环化酶A（GC-A）和C受体的存在情况。用ANP（1和3×10⁻⁷M）对睾丸进行体外灌注，可刺激睾酮生成，且具有时间和剂量依赖性。另一方面，ANP会减弱LH诱导的睾酮分泌。使用特异性C受体配体cANF也获得了类似的结果，表明C受体参与了这种反应。总之，ANP在体外灌注的大鼠睾丸中刺激睾酮生成，但降低LH诱导的睾酮生成，这种作用似乎涉及C受体。就此而言，我们的结果表明大鼠睾丸中存在一个局部且复杂的肽能系统，涉及ANP及其受体，它们可能对雄激素生物合成具有重要调节作用。
