title: Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.
abstract: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism.
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Clinical Pathology, Odense University Hospital, Odense, Denmark; University Library of Southern Denmark, University of Southern Denmark, Odense, Denmark. Electronic address: mette_e@bib.sdu.dk.
authors.forename: Mette Brandt
authors.initials: MB
authors.lastname: Eriksen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Glintborg
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael Friberg Bruun
authors.initials: MF
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
authors.forename: Marianne Antonius
authors.initials: MA
authors.lastname: Jakobsen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brusgaard
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Denmark; Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark; Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Gaster
mesh_terms: D000328:Adult; D001141:Aromatase / Q000096:biosynthesis*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D013739:Testosterone; D001141:Aromatase; D005947:Glucose
keywords: Glucose transport; Insulin resistance; Myotubes; PCOS; Steroid hormone synthesis