17-Beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma. A new development in intracrinology

Hironobu Sasano, Takashi Suzuki, Junji Takeyama, Hiroki Utsunomiya, Kiyoshi Ito, Naohiro Ariga, Takuya Moriya

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of various sex steroid-dependent neoplasms including breast and endometrial carcinoma. 17β-Hydroxysteroid dehydrogenase (17β-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone (E), and thereby serve to modulate the tissue levels of bioactive E2. 17β-HSD type 1 primarily catalyzes the reduction of E1 to E2, whereas 17β-HSD type 2 primarily catalyzes the oxidation of E2 to E1. In the human breast and its disorders, 17β-HSD type 1 is expressed in proliferative diseases without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17β-HSD type 2 is not detected in any of the lesions. In addition, 17β-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E1, produced as a result of in situ aromatization, to E2, a biologically potent estrogen, and exerts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17β-HSD type 2 is expressed, but not 17β-HSD type 1. 17β-HSD type 2 is expressed in the secretory phase but not in any proliferative phase in the endometrial mucosa. The enzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation has been detected between 17β-HSD type 2 immunoreactivity and age (p < 0.02). These results indicate that oxidation of E2 to E1 is dominant in endometrial carcinoma, 17β-HSD types 1 and 2 play an important role in the regulation of in situ estrogen production in breast and endometrial carcinoma. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)5-12
Number of pages8
JournalOncology
Volume59
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • 17β-Hydroxysteroid dehydrogenase
  • Breast
  • Endometrium
  • Estrogen
  • Intracrinology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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