title: Differential effects of down-regulated steroidogenic factor-1 on basal and angiotensin II-induced aldosterone secretion.
abstract: Aldosterone synthase (CYP11B2) is responsible for the final step in aldosterone synthesis and is importantly regulated by angiotensin-II (Ang II) through diverse pathways. However, under pathological conditions, such as in hyperaldosteronism, the regulation becomes disordered. The transcription factor steroidogenic factor-1 (SF-1) is important in regulating the endocrine system and is overexpressed in aldosterone-producing adenoma (APA), a common cause of hyperaldosteronism. Overexpression of SF-1 has been extensively studied, but little in-depth information is available regarding the effects of inhibitory SF-1 on CYP11B2 and Ang II. In this paper, we have investigated the roles of down-regulated SF-1 in basal and Ang II-induced CYP11B2 expression using SF-1-specific short hairpin RNA. Inhibitory SF-1 was found to decrease the sensitivity of CYP11B2 and aldosterone to Ang II stimulation, whereas a down-regulation of SF-1 enhanced basal CYP11B2 expression and aldosterone production in H295R cells. Considering these differential effects of SF-1 on aldosterone production, these results might provide a new insight into the understanding of hyperaldosteronism.
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ouyang
authors.forename: D
authors.initials: D
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Shi
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism / Q000503:physiopathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D054339:Steroidogenic Factor 1; D000804:Angiotensin II; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2