Ovarian renin--angiotensin system-regulating aminopeptidases are involved in progesterone overproduction in rats with mammary tumours induced by N-methyl nitrosourea.
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.


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.


CONCLUSIONS
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.
Del Pilar Carrera
María
M
Department of Health Sciences, University of Jaén, Campus Universitario Las Lagunillas, E-23071, Jaén, Spain. pcarrera@ujaen.es
Ramírez-Expósito
María Jesús
MJ
García
María Jesús
MJ
Mayas
María Dolores
MD
Martínez-Martos
José Manuel
JM
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000097:blood; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008770:Methylnitrosourea; D010053:Ovary / Q000201:enzymology / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea; D000626:Aminopeptidases