INVOLVEMENT OF ANGIOTENSIN-II RECEPTOR SUBTYPES DURING TESTICULAR DEVELOPMENT IN RATS

Expression of testicular angiotensin II (AT2) receptors in Sprague-Daw ley rats at various stages of development (1 and 5 days, 2. 3. 4 and 7 weeks postnatal) were studied by in vitro autoradiography and Norther n blot analysis,. The receptors were labelled with I-125[Sar(1), Ile(8 )]AT2 and differentiated into two subtypes according to their suscepti bility to ATI (losartan, 5 mu M) or AT2 (PD123319. 5 mu M) antagonists , Total AT2 receptor binding in the testis was highest at 1 day oi ags (8.12 +/- 0.35 fmol/mg protein, mean +/- secEM, n = 8) and decreased gradually thereafter (5 days: 6.9 +/- 0.41. 2 weeks: 2.85 +/- 0.10, 3 weeks: 1.64 +/- 0.19, 4 weeks: 0.76 +/- 0.09, 6 weeks: (0.77 +/- 0.09 fmol/mg protein. n = 8-11). AT2 receptor binding was strikingly abunda nt in 1-day old rat testis (6.98 +/- 0.34 fmol/mg protein), while cons iderably less AT1 receptor binding (1.46 +/-19 fmol/mg protein) was ob served. The relative amounts of each subtype did not change for the fi rst 3 weeks but the 4-week-old rat testis contained almost exclusively AT1 receptors (0.63 +/- 0.05 fmol/mg protein). Northern blot analysis showed that mRNA expression of both AT1 and AT2 types decreased with age. Microscopic emulsion autoradiography was undertaken to clarify th e localization of binding. At 10 days of age, both ATI and AT2 recepto rs were present ill the interstitial area, whereas seminiferous tubule s contained mainly AT2 receptors. At 7 weeks of age, no significant bi nding was observed in the seminiferous tubule and the interstitial are a contained AT1 receptors exclusively. These results demonstrate expre ssion of AT2 receptor in the rapidly growing testis and suggest that c hange iii thr levels of AT2 receptor subtypes ma) be relevant to devel opment and/or growth of the testis.