title: 11-Ketotestosterone Is a Major Androgen Produced in Human Gonads.
abstract: 11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans.
  
  
  
  The objective of this study was to clarify the production and properties of 11-KT in human. Design, Participants, and Methods: Expression of cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells.
  
  
  
  Cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20 times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/estrogen receptor -mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when androgen receptor was transfected into MCF-7 cells.
  
  
  
  The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a nonaromatizable androgen.
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imamichi
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Koh-Ichi
authors.initials: KI
authors.lastname: Yuhki
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Orisaka
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kitano
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Departments of Pharmacology (Y.I., K.-i.Y., F.U.) and Biochemistry (T.T., T.Y.), Asahikawa Medical University, Hokkaido 078-8510, Japan; Departments of Biochemistry (Y.I., K.Mi.) and Obstetrics and Gynecology (M.O.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Department of Materials and Life Science (T.K.), Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan; Department of Biochemistry and Medical Education Center (K.Mu.), Keio University School of Medicine, Tokyo 160-8582, Japan; and Department of Reproduction (A.U.), National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yazawa
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D013739:Testosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D013799:Theca Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C003600:11-ketotestosterone