**Author details**

the insertion of a modified ACE allele through homologous recombination [58], present distinctly low blood pressure, deeply impaired kidneys, and a high infertility index. In addition, ANG II

Additionally, angiotensinogen is present in testicular tissue in the majority of mammals, excluding rats [37, 60–66]. Molecular investigations have found that AT1A is the predominantly expressed receptor in mouse testis [67] and ANG II receptor was also found to be acting on Leydig cells of mammals [59, 68]. Likewise, ANG I and ANG II are also present in rat epididymis and the level of ANG II in the epididymis can be clearly reduced after efferent duct ligation [38, 40, 69]. ANG receptors AT1 and AT2 have been detected in rat epididymis [70], where the presence of AT1 receptors is higher than AT2 receptors, and both receptors are much more numerous in fully mature rat epididymis than in younger stages. AT1 receptors

There is evidence of linked RAS regulation between the circulatory system and testes, as hypophysectomy decreases renin levels in the testes while slightly increasing plasma renin [71]. Estrogen and other gonadotrophin hyperstimulation treatments can deplete renin signalization in Leydig cells [72, 73]. On the other hand, renin activity, as well as ANG production, can be increased in Leydig cells in vitro by human chorionic gonadotropin (hCG) or bovine luteinizing hormone administration [74]. There is also evidence that renin levels in

In 1998, Hirai et al. [76] verified that AT1 and AT2 expression in rat testes depends on the pituitary action, since after hypophysectomy the gene expression of both receptors was significantly increased. In addition, chorionic gonadotropin has been shown to reduce AT1 and AT2 gene expression. Furthermore, the AT2 expression in rat testes is variable according to the developmental stage of the male. For instance, as the aging process progresses the expression of both AT1 and AT2 substantially decreases [77]. Similarly, we can observe plenty of ANG II receptors in non-differentiated mesenchymal cells of the interstitium in immature testes, but

ANG is one of the peptide hormones in the epididymis responsible for stimulating the secretion of anion and fluid [39]. Some evidence suggests that the majority of its action is attributed to ANG II action on the apical surface of the epididymal epithelium, in which it may exert an

In summary, the variability of the RAS in the testes or epididymis is gradually affected as development progresses, with a decrease in concentrations of AT1 and AT2 receptors and also a reduction in ANG II receptor binding (predominantly AT2 receptor) in the testes. By adult-

Funding for studies was provided by the São Paulo Research Foundation (FAPESP; grant

can increase sperm motility and AT1 receptor antagonists can inhibit this action [59].

were also found in primary spermatogonia and spermatid tails [59].

ANG II binding systematically decreases throughout development [68].

effect through interaction with the AT1 receptor [70, 78].

hood, the testes contain almost exclusively AT1 receptors [77].

plasma are also increased by hCG [75].

76 Renin-Angiotensin System - Past, Present and Future

**Acknowledgments**

#2011/50593-2 and #2013/11480-3).

Anthony C.S. Castilho¹\*, Patrícia K. Fontes², Fernanda F. Franchi², Priscila H. Santos² and Eduardo M. Razza²


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