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Expression and Modulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Rat Cardiocytes and after Myocardial Infarction

Division of Endocrinology and Diabetology, University Hospital, CH-1211 Geneva 14, Switzerland; and Institut National de la Santé et de la Recherche Médicale, Unité-127, Hôpital Lariboisière (J.S.S., C.D.), 75475 Paris, France

Address all correspondence and requests for reprints to: Prof. A. Capponi, Division of Endocrinology and Diabetology, University Hospital, 24 rue Micheli du Crest, CH-1211 Geneva 14, Switzerland. E-mail: alessandro.capponi{at}medecine.unige.ch.

We examined whether the mRNA for steroidogenic acute regulatory (StAR) protein, a crucial factor in the rate-limiting step of aldosterone biosynthesis, is expressed and regulated in rat heart. We performed quantitative RT-PCR for StAR mRNA in an in vitro and an in vivo model: purified rat neonatal cardiomyocytes in primary culture and myocardial infarction (MI) in the rat. StAR mRNA was expressed in cultured cardiomyocytes, and angiotensin II (10 nM) increased it in a time-dependent fashion (132 ± 2.7% of controls after 24 h; n = 3; P < 0.05). Concomitantly, angiotensin II stimulated aldosterone production in the culture medium from 32.6 ± 6.1 to 54 ± 12.7 fmol/mg protein after 24 h (n = 8; P < 0.05). StAR mRNA levels in cardiomyocytes were dramatically reduced after 24-h treatment with dexamethasone in a concentration-dependent manner (50% inhibitory concentration, 10 nM); maximal inhibition (to 15 ± 6% of control; P < 0.001; n = 6) was achieved with 100 nM dexamethasone. This inhibition was prevented by RU486. In the rat MI model, StAR mRNA was also present in control heart tissue and was increased 2.4-fold in the noninfarcted area of the left ventricle after MI (n = 6; P < 0.01). This effect was completely prevented by treatment with losartan (8 mg/kg·d) and spironolactone (80 mg/kg·d), which reduced StAR mRNA levels to values not different from those in non-MI controls. Thus, the mRNA for an indispensable factor in aldosterone biosynthesis, the StAR protein, is expressed in the rat heart and is up-regulated after MI. These results support the view of a local synthesis of aldosterone in the heart and of intracrine/paracrine deleterious effects of the mineralocorticoid in heart failure.

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