title: Human adrenal cells that express both 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) contribute to adrenal androstenedione production.
abstract: Androstenedione is one of several weak androgens produced in the human adrenal gland. 3β-Hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) are both required for androstenedione production. However, previous studies demonstrated the expression of HSD3B2 within the zona glomerulosa (ZG) and fasciculata (ZF) but low levels in the zona reticularis. In contrast, CYB5A expression increases in the zona reticularis (ZR) in human adrenal glands. Although their colocalization has been reported in gonadal theca and Leydig cells this has not been studied in the human adrenal. Therefore, we immonolocalized HSD3B2 and CYB5A in normal human adrenal glands and first demonstrated their co-expression in the cortical cells located at the border between the ZF and ZR in normal human adrenal. Results of in vitro studies using the human adrenal H295R cells treated with the HSD3B2 inhibitor, trilostane, also demonstrated a markedly decreased androstenedione production. Decreasing CYB5A mRNA using its corresponding siRNA also resulted in significant inhibition of androstenedione production in the H295R cells. These findings together indicate that there are a group of cells co-expressing HSD3B2 and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex, and these hybrid cortical cells may play an important role in androstenedione production in human adrenal gland.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. yasu-naka@patholo2.med.tohoku.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yewei
authors.initials: Y
authors.lastname: Xing
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Hui
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kurotaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.forename: Tony
authors.initials: T
authors.lastname: Cohen
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology / Q000378:metabolism*; D000735:Androstenedione / Q000096:biosynthesis*; D015786:Cytochromes b5 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000735:Androstenedione; D015786:Cytochromes b5; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase