Regulation of aminopeptidases by the renin–angiotensin system: monitoring seasonal variations in red deer and fallow deer from a Mediterranean ecosystem A. Galán-Ocaña A , M. J. Ramírez-Expósito A , J. M. Martínez-Martos A , S. Tellado B and C. Azorit B,C A Experimental and Clinical Physiopathology Research Group, Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, 23071, Jaén, Spain. B Department of Animal and Vegetal Biology and Ecology, Faculty of Experimental Sciences, University of Jaén, 23071, Jaén, Spain. C Corresponding author. Email: cazorit@ujaen.es Abstract. The circulating renin–angiotensin system (RAS) is well known for its systemic role in the regulation of blood pressure, renal hemodynamics and fluid homeostasis. However, in mammals several organs also contain a local RAS, including male and female reproductive tissues. In the present study we analysed serum from a free-living population of red deer (Cervus elaphus hispanicus) and fallow deer (Dama dama) to determine the activity of four RAS-regulating aminopeptidases (aminopeptidase A, aspartyl aminopeptidase, aminopeptidase N and aminopeptidase B) as part of a study of annual cycles of growth and condition. Our aim was to detect seasonal variations in the activities of these aminopeptidases and their relationship to the reproductive behaviour of both species in a Mediterranean environment. In both males and females there was a maximum peak of activity in autumn. A second peak was detected in spring for males while in females activity was also higher in summer. These changes may be related to a different endocrine status according to their seasonal cycle, the decreased photoperiod in autumn and the normal timing of the seasonal growth cycle. Thus, changes in the activity of RAS-regulating aminopeptidases could reflect the functional role of angiotensins through the annual cycle of both species, also suggesting an important role of these peptide hormones in the regulation of these biological processes. Received 16 January 2012, accepted 27 April 2012, published online 5 June 2012 Introduction It is well known that the renin–angiotensin system (RAS) plays an important role in mammals in general homeostasis including the regulation of systemic blood pressure and of fluid and electrolyte balance (Rozenfeld et al. 2003). As well as its classical roles, a local RAS has been found in both male and female reproductive systems in several mammals. Thus, in females, binding sites for angiotensin II (AngII) have been identified in rodent ovarian follicles (Speth et al. 1986; Husain et al. 1987) and corpora lutea (Pepperell et al. 1993, 2006). Renin- and prorenin-like activities have been shown in bovine follicles (Schultze et al. 1989), and angiotensin-converting enzyme (ACE) is also present in rodent ovarian follicles and corpora lutea (Speth and Husain 1988). Furthermore, evidence has been accumulating that AngII locally regulates ovulation, oocyte maturation (Kuo et al. 1991; Yoshimura et al. 1992) and steroidogenesis (Yoshimura et al. 1996). These findings suggest that the ovarian RAS may function independently or in conjunction with the systemic RAS, and regulate ovarian function through the paracrine/autocrine actions of AngII. In males, several studies have also provided evidence for the presence of the RAS in reproductive tissues, such as the detection of immunoreactive renin in the Leydig cells of rat and human testes (Parmentier et al. 1983; Naruse et al. 1985). Similarly, other studies have shown the presence of renin, angiotensin I (AngI), AngII and angiotensin receptors in normal rat Leydig cells and a murine Leydig cell line (Pandey et al. 1984a, 1984b; Pandey and Inagami 1986). Furthermore, ACE activity has been identified in testes, localised predominantly in the germinal cells. Only minor activity has been found in purified adult rodent Leydig and Sertoli cells (Velletri 1985; Velletri et al. 1985), where the existence of a new ACE homologue (ACE2) has been described (Douglas et al. 2004). A putative role has therefore been proposed for AngII in modulating the action of gonadotropin in Leydig cells, thus modulating steroidogenesis and testosterone production (Khanum and Dufau 1988). A main role for AngII has therefore been proposed in both male and female steroidogenesis. However, although AngII has normally been considered the main bioactive peptide of the RAS, some studies suggest that the major player is AngIII (Reaux et al. 2000, 2001; Reudelhuber 2005). In fact, AngIII has most of the properties of AngII and shares the same receptors (Szczepa nska-Sadowska 1996; Barrett et al. 2004). AngIII CSIRO PUBLISHING Animal Production Science, 2012, 52, 761–765 http://dx.doi.org/10.1071/AN12023 Journal compilation Ó CSIRO 2012 www.publish.csiro.au/journals/an