title: Progesterone metabolism in adipose cells.
abstract: The aim of the present study was to investigate pathways of progesterone metabolism in human adipose cells. Adipose tissue samples from the omental (OM) and subcutaneous (SC) fat compartments were surgically obtained in women. In isolated mature adipocytes, progesterone was converted to 20alpha-hydroxyprogesterone as the main metabolite, most likely through the activity of aldo-keto reductases 1C1, 2 and 3 (20alpha-HSD, 3alpha-HSD type 3 and 17beta-HSD type 5, respectively). In cultured preadipocytes, progesterone was converted to several metabolites identified using bidimensional thin layer chromatography, with or without the dual inhibitor of 5alpha-reductase type 1 and 2 (17beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5alpha-androstan-3-one (4-MA)). Major metabolites identified in OM and SC preadipocytes which were incubated for 24h with (14)C-labelled progesterone were 20alpha-hydroxyprogesterone, 5alpha-pregnane-3alpha/beta-ol-20-one, 5alpha- and 5beta-pregnanedione, 5alpha- and 5beta-pregnane-20alpha-ol-3-one, 5alpha-pregnane-3alpha/beta-ol-20-one and 5beta-pregnane-3alpha/beta-20alpha-diol. Induction of preadipocyte differentiation increased expression levels of AKR1C1 and modified the pattern of progesterone metabolism substantially, leaving 20alpha-hydroxyprogesterone as the main metabolite generated. On the other hand, progesterone itself showed no consistent effect on adipocyte differentiation. In conclusion, preadipocytes and lipid-storing, mature adipocytes efficiently generate progesterone metabolites in women, which is consistent with rather modest effects progesterone on abdominal fat cell differentiation.
authors.affiliation: Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Quebec City, Canada.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mélanie
authors.initials: M
authors.lastname: Nadeau
authors.forename: Frédérick
authors.initials: F
authors.lastname: Faucher
authors.forename: Odette
authors.initials: O
authors.lastname: Lescelleur
authors.forename: Simon
authors.initials: S
authors.lastname: Biron
authors.forename: Marleen
authors.initials: M
authors.lastname: Daris
authors.forename: Caroline
authors.initials: C
authors.lastname: Rhéaume
authors.forename: Van
authors.initials: V
authors.lastname: Luu-The
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
mesh_terms: D015089:20-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D009852:Omentum; D011374:Progesterone / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D011374:Progesterone; D015089:20-Hydroxysteroid Dehydrogenases; C115140:3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase