Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery

Gonda Konings, Linda Brentjens, Bert Delvoux, Tero Linnanen, Karlijn Cornel, Pasi Koskimies, Marlies Bongers, Roy Kruitwagen, Sofia Xanthoulea, Andrea Romano*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Citations (Web of Science)

Abstract

Our understanding of the intracrine (or local) regulation of estrogen and other steroid synthesis and degradation expanded in the last decades, also thanks to recent technological advances in chromatography mass-spectrometry. Estrogen responsive tissues and organs are not passive receivers of the pool of steroids present in the blood but they can actively modify the intra-tissue steroid concentrations. This allows fine-tuning the exposure of responsive tissues and organs to estrogens and other steroids in order to best respond to the physiological needs of each specific organ. Deviations in such intracrine control can lead to unbalanced steroid hormone exposure and disturbances. Through a systematic bibliographic search on the expression of the intracrine enzymes in various tissues, this review gives an up-to-date view of the intracrine estrogen metabolisms, and to a lesser extent that of progestogens and androgens, in the lower female genital tract, including the physiological control of endometrial functions, receptivity, menopausal status and related pathological conditions. An overview of the intracrine regulation in extra gynecological tissues such as the lungs, gastrointestinal tract, brain, colon and bone is given. Current therapeutic approaches aimed at interfering with these metabolisms and future perspectives are discussed.

Original languageEnglish
Article number940
Number of pages51
JournalFrontiers in Pharmacology
Volume9
DOIs
Publication statusPublished - 19 Sep 2018

Keywords

  • intracrinology
  • endometrium
  • estrogens
  • lungs
  • gastrointestinal tract
  • central nervous system
  • bone
  • MESSENGER-RNA EXPRESSION
  • HUMAN TEMPORAL-LOBE
  • CENTRAL-NERVOUS-SYSTEM
  • CELL LUNG-CANCER
  • KETO REDUCTASE SUPERFAMILY
  • POLYCYSTIC-OVARY-SYNDROME
  • AROMATASE-DEFICIENT MICE
  • 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-2 EXPRESSION
  • SULFATASE INHIBITOR IROSUSTAT
  • EPILEPTIC HUMAN HIPPOCAMPUS

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