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- Title
Aldo Keto Reductase 1B7 and Prostaglandin F<sub>2α</sub> Are Regulators of Adrenal Endocrine Functions.
- Authors
Lambert-Langlais, Sarah; Pointud, Jean-Christophe; Lefrançois-Martinez, Anne-Marie; Volat, Fanny; Manin, Michèle; Coudoré, François; Val, Pierre; Sahut-Barnola, Isabelle; Ragazzon, Bruno; Louiset, Estelle; Delarue, Catherine; Lefebvre, Hervé; Urade, Yoshihiro; Martinez, Antoine
- Abstract
Prostaglandin F2α(PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2αsynthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2αbiosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2αbut expressed different biosynthetic isozymes. In chromaffin cells, PGF2αsecretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2αsecretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2αrelease and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2αreceptor was only detected in chromaffin cells, making medulla the primary target of PGF2αaction. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2αrepressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2αmay be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cellspecific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal.
- Subjects
PROSTAGLANDINS; INFLAMMATORY mediators; PARTURITION; MAMMALS; BIOSYNTHESIS; ADRENAL glands; ENDOCRINE glands; CYCLOOXYGENASES; CHROMAFFIN cells
- Publication
PLoS ONE, 2009, Vol 4, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0007309