title: Type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) contributes to testosterone production in the adrenal reticularis.
abstract: BACKGROUND
  The human adrenal gland produces small amounts of testosterone that are increased under pathological conditions. However, the mechanisms through which the adrenal gland produces testosterone are poorly defined.
  
  
  OBJECTIVE
  Our objective was to define the role of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in human adrenal production of testosterone.
  
  
  METHODS
  Adrenal vein sampling was used to confirm ACTH stimulation of adrenal testosterone production. Adrenal expression of AKR1C3 was studied using microarray, quantitative real-time RT-PCR, and immunohistochemical analyses. AKR1C3 knockdown was accomplished in cultured adrenal cells (H295R) using small interfering RNA, followed by measurement of testosterone production.
  
  
  RESULTS
  Acute ACTH administration significantly increased adrenal vein testosterone levels. Examination of the enzymes required for the conversion of androstenedione to testosterone using microarray analysis, quantitative real-time RT-PCR, and immunohistochemistry demonstrated that AKR1C3 was present in the adrenal gland and predominantly expressed in the zona reticularis. Decreasing adrenal cell expression of AKR1C3 mRNA and protein inhibited testosterone production in the H295R adrenal cell line.
  
  
  CONCLUSIONS
  The human adrenal gland directly secretes small, but significant, amounts of testosterone that increases in diseases of androgen excess. AKR1C3 is expressed in the human adrenal gland, with higher levels in the zona reticularis than in the zona fasciculata. AKR1C3, through its ability to convert androstenedione to testosterone, is likely responsible for adrenal testosterone production.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hornsby
authors.forename: Peter
authors.initials: P
authors.lastname: Casson
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.forename: Yewei
authors.initials: Y
authors.lastname: Xing
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kennedy
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey