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This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/E221    most recent 00205.2005v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Pepperell, J. R. Articles by Merino, M. Search for Related Content PubMed PubMed Citation Articles by Pepperell, J. R. Articles by Merino, M.

Localized accumulation of angiotensin II and production of angiotensin-(1–7) in rat luteal cells and effects on steroidogenesis

¹Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, Connecticut; and ²Department of Pathology and ³Department of Pediatrics, Brown University Medical School, Women & Infants Hospital, Providence, Rhode Island

Submitted 9 May 2005 ; accepted in final form 26 January 2006

These studies aim to investigate subcellular distribution of angiotensin II (ANG II) in rat luteal cells, identify other bioactive angiotensin peptides, and investigate a role for angiotensin peptides in luteal steroidogenesis. Confocal microscopy showed ANG II distributed within the cytoplasm and nuclei of luteal cells. HPLC analysis showed peaks that eluted with the same retention times as ANG-(1–7), ANG II, and ANG III. Their relative concentrations were ANG II ANG-(1–7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease. Phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, did not affect peptide accumulation. Quinapril, ZPP, PCMS, and PMSF, as well as losartan and PD-123319, the angiotensin receptor type 1 (AT₁) and type 2 (AT₂) receptor antagonists, were used in progesterone production studies. ZPP significantly reduced luteinizing hormone (LH)-dependent progesterone production (P < 0.05). Quinapril plus ZPP had a greater inhibitory effect on LH-stimulated progesterone than either inhibitor alone, but this was not reversed by exogenous ANG II or ANG-(1–7). Both PCMS and PMSF acutely blocked LH-stimulated progesterone, and PCMS blocked LH-sensitive cAMP accumulation. Losartan inhibited progesterone production in permeabilized but not intact luteal cells and was reversed by ANG II. PD-123319 had no significant effect on luteal progesterone production in either intact or permeabilized cells. These data suggest that steroidogenesis may be modulated by angiotensin peptides that act in part through intracellular AT₁ receptors.

signaling; protease inhibitor; angiotensin antagonist