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Ovarian renin--angiotensin system-regulating aminopeptidases are involved in progesterone overproduction in rats with mammary tumours induced by N-methyl nitrosourea. Del Pilar Carrera M et al. A local renin-angiotensin system (RAS) has been found in ovary. This ovarian RAS may regulate ovarian steroidogenesis. Ample studies show that the ovarian hormones estradiol (E2) and progesterone (P) are strongly implicated in the development of breast cancer. MATERIALS AND METHODS: The aim of the present work was to elucidate if alterations in ovarian RAS, analyzed through their proteolytic regulatory enzymes aminopeptidase A (APA), B (APB) and N (APN), could be responsible for an altered steroidogenesis in rats with mammary tumours induced by N-methyl nitrosourea (NMU). RESULTS: We describe here a highly significant increase of serum P levels in NMU-treated rats, concomitantly with an increase in ovarian aspartyl and glutamyl aminopeptidase activities (named together as APA activity). Moreover, we did not find changes in APB or APN activities, suggesting an increased metabolism from Ang II to Ang III and a decreased catabolism of Ang III. CONCLUSION: The relationship between ovarian RAS and P overproduction in a rat model of mammary carcinogenesis indicates ovarian RAS as a new potential target in breast cancer therapy.
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Localization of angiotensin II, the AT1 receptor, angiotensin-converting enzyme, aminopeptidase A, adipocyte-derived leucine aminopeptidase, and vascular endothelial growth factor in the human ovary throughout the menstrual cycle. Harata T et al. OBJECTIVE: To assess the expression and cellular distribution of angiotensin II (Ang II), angiotensin type 1 receptor (AT1R), angiotensin-converting enzyme (ACE), aminopeptidase A (APA), adipocyte-derived leucine aminopeptidase (A-LAP), and vascular endothelial growth factor (VEGF) in human ovarian tissue during the menstrual cycle. DESIGN: Ovarian tissues (n = 52) and corpora lutea (n = 34) were obtained from patients undergoing hysterectomy/oophorectomy, and tissue sections were immunostained for each antigen. SETTING: University hospital. PATIENT(S): Patients undergoing hysterectomy or oophorectomy for benign conditions. INTERVENTION(S): Immunostaining of tissue sections using antibodies to each antigen. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence, distribution, and cellular localization. RESULT(S): The luteal tissue is the major site of Ang II, ACE, AT1R, and VEGF, with highest staining intensity found during the midluteal phase and at pregnancy. The AT1R was found in theca cells. The APA was strongly immunolocalized in pericytes. Immunolocalization of AT1R was almost similar to that of VEGF including oocytes in the primordial and intermediate follicles. CONCLUSION(S): The expression and distinct pattern of the cellular localization of Ang II and its related proteins in human ovarian tissue during folliculogenesis and in the luteal tissue suggest their roles in the growth and differentiation of theca, granulose, and luteal cells.
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