title: Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions.
abstract: BACKGROUND
  Aberrant sex steroid signaling is suggested to promote endometriosis growth by several mechanisms, and the tissue concentrations of sex steroids are key determinants of the hormone action. However, their concentrations are only superficially known in the endometrium and endometriosis lesions.
  
  
  OBJECTIVE
  This study sought to evaluate whether the tissue steroid hormone concentrations in endometriosis differ from the endometrium or serum.
  
  
  METHODS
  Steroid analysis of serum and tissue specimens of women with endometriosis (n = 60) and healthy controls (n=16) was measured, and supporting data from quantitative RT-PCR for steroidogenic enzymes and explant cultures of a subset of specimens is provided.
  
  
  RESULTS
  Endometrial tissue progesterone (P4) concentrations reflected the serum P4 levels during the menstrual cycle, whereas in endometriosis lesions, the cycle-dependent change was missing. Remarkably high tissue T concentrations were measured in endometriosis lesions independent of the cycle phase, being 5-19 times higher than the corresponding serum levels. Tissue/serum ratio of T was further increased in patients with contraceptive medication. The altered tissue steroid concentrations in endometriosis were in line with the expression of various steroidogenic enzymes in the lesions, of which HSD3B2 showed constantly high expression, whereas CYP11A1 expression was low. Furthermore, the high concentration of sex steroids detected in the ovarian lesions involves their production by the lesion and by the adjacent ovarian tissue.
  
  
  CONCLUSIONS
  Endometriosis lesions present with progestin and androgen metabolism, which are different from that of the endometrium, and the lesions are characterized by high tissue T and a loss of cyclical changes in tissue P4 concentration.
authors.affiliation: Department of Physiology (K.H., T.S.-H., D.L., M.S., M.A., A.P., M.P.), Institute of Biomedicine, University of Turku, 20014 Turku, Finland; Department of Obstetrics and Gynecology (K.H., P.S., A.P.), University of Turku, 20014 Turku, Finland; School of Pharmacy, University of Eastern Finland (P.K.-R., M.R.H., S.A.), 70211 Kuopio, Finland; ANZAC Research Institute (R.D., D.J.H.), Concord Hospital, University of Sydney, 2139, Australia; Institute for Molecular Medicine Finland (D.L., T.A.), University of Helsinki, 00014 Helsinki, Finland; Department of Pathology (H.K.), Institute of Biomedicine, University of Turku, 20014 Turku, Finland; Turku Center for Disease Modeling (M.P.), University of Turku, 20014 Turku, Finland; and Institute of Medicine (M.P.), The Sahlgrenska Academy, Gothenburg University, 413 45 Gothenburg, Sweden.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Huhtinen
authors.forename: Taija
authors.initials: T
authors.lastname: Saloniemi-Heinonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Keski-Rahkonen
authors.forename: Reena
authors.initials: R
authors.lastname: Desai
authors.forename: Daniel
authors.initials: D
authors.lastname: Laajala
authors.forename: Mia
authors.initials: M
authors.lastname: Ståhle
authors.forename: Merja R
authors.initials: MR
authors.lastname: Häkkinen
authors.forename: Michael
authors.initials: M
authors.lastname: Awosanya
authors.forename: Pia
authors.initials: P
authors.lastname: Suvitie
authors.forename: Harry
authors.initials: H
authors.lastname: Kujari
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004715:Endometriosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013739:Testosterone; D011374:Progesterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme