This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rossi, F. Articles by Santiemma, V. Search for Related Content PubMed PubMed Citation Articles by Rossi, F. Articles by Santiemma, V.

Angiotensin II Stimulates Contraction and Growth of Testicular Peritubular Myoid Cells in Vitro

Dipartimento di Fisiopatologia Medica, Università di Roma "La Sapienza" Facoltà di Medicina, 00161 Rome, Italy

Address all correspondence and requests for reprints to: Prof. Vittorio Santiemma, Dipartimento di Fisiopatologia Medica, V Clinica Medica, Policlinico Umberto I, Università di Roma "La Sapienza," Viale del Policlinico, 00161 Roma, Italy. E-mail: . vittorio.santiemma{at}uniroma1.it

Seminiferous tubule contraction, an important step in the regulation of spermatogenesis and testicular sperm output, is regulated by several agonists. In the present paper, we investigated whether angiotensin II (Ang II) may have a place among them.

In binding experiments performed to assess the presence of specific receptors in rat peritubular myoid cells (TPMC), binding of ¹²⁵I-Ang II to TPMC was saturable in a time-dependent manner. Competition binding experiments performed with Losartan and PD 123319 showed that Losartan was able to inhibit the binding of ¹²⁵I-Ang II, whereas PD 123319 was ineffective.

Ang II induced a dose-dependent rise in intracellular Ca²⁺. Depletion of intracellular calcium stores by thapsygargin resulted in a lower rise of intracellular calcium, and the L-type voltage-operated calcium channel (VOCC-L) blocker verapamil abolished the Ca²⁺ influx in rat TPMC. Altogether, these findings indicate that the Ang II-induced increase in [Ca²⁺]_i involves both extracellular influx and Ca²⁺ release from intracellular stores.

Ang II induced a dose-dependent TPMC contraction, and Losartan and not PD 123319 inhibited the response. Ang II-induced contraction was inhibited by adrenomedullin, previously shown to antagonize endothelin 1-provoked contraction in those cells.

Ang II elicited ³H-thymidine DNA incorporation and proliferation in a dose-dependent manner in TPMC. Losartan and both MAPK inhibitor PD 98059 and tyrosine kinase inhibitor AG18 were able to inhibit Ang II-induced ³H-thymidine uptake and cell proliferation.

In conclusion, the present study documents that angiotensin II, the active mediator of the tissue and circulating renin-angiotensin system present in the mammalian testis, induces contraction, growth and rise in intracellular calcium in rat peritubular myoid cells via angiotensin II type 1 receptors, and suggests that Ang II is involved in the paracrine regulation of the seminiferous tubule function.

This article has been cited by other articles:

				C. Schell, M. Albrecht, C. Mayer, J. U. Schwarzer, M. B. Frungieri, and A. Mayerhofer Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-{alpha} Endocrinology, April 1, 2008; 149(4): 1678 - 1686. [Abstract] [Full Text] [PDF]

				L. Hunyady and K. J. Catt Pleiotropic AT1 Receptor Signaling Pathways Mediating Physiological and Pathogenic Actions of Angiotensin II Mol. Endocrinol., May 1, 2006; 20(5): 953 - 970. [Abstract] [Full Text] [PDF]

				E. Karteris, J. Chen, and H. S. Randeva Expression of Human Prepro-Orexin and Signaling Characteristics of Orexin Receptors in the Male Reproductive System J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1957 - 1962. [Abstract] [Full Text] [PDF]