title: Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels.
abstract: BACKGROUND
  Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described.
  
  
  OBJECTIVE
  The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes.
  
  
  METHODS
  Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study.
  
  
  METHODS
  We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes.
  
  
  RESULTS
  Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions.
  
  
  CONCLUSIONS
  Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.
authors.affiliation: University of Turku, 20014 Turku, Finland. matti.poutanen@utu.fi
authors.forename: Kaisa
authors.initials: K
authors.lastname: Huhtinen
authors.forename: Reena
authors.initials: R
authors.lastname: Desai
authors.forename: Mia
authors.initials: M
authors.lastname: Ståhle
authors.forename: Anu
authors.initials: A
authors.lastname: Salminen
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D000328:Adult; D004715:Endometriosis / Q000097:blood / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D004970:Estrone / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D010049:Ovarian Diseases / Q000097:blood / Q000378:metabolism*; D010532:Peritoneal Diseases / Q000097:blood / Q000378:metabolism*
chemical_list: D004970:Estrone; D004958:Estradiol