title: Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy.
abstract: OBJECTIVE
  Although natural menopause is associated with loss of ovarian estrogen production, this life phase is followed by a significant increase in estrogen-related cancers, namely breast and endometrial cancer. These tissues, as well as adipose, skeletal, and vascular tissues and the brain are important sites of postmenopausal estrogen production. Circulating C19 steroid precursors are essential substrates for extragonadal estrogen synthesis; however, the levels of these androgenic precursors decline markedly with advancing age. This implies an increase in capacity for extragonadal tissues to produce estrogen with age.
  
  
  METHODS
  To explore this, and the effects of the menopause transition and postmenopausal estrogen therapy on extragonadal estrogen biosynthesis, we have compared the expression of the aromatase gene and estrogen (ER) and androgen receptors (AR) in subcutaneous abdominal and gluteal fat taken from premenopausal (group 1: n = 11), postmenopausal (group 2: n = 10), and postmenopausal women taking estrogen therapy (group 3: n = 10). All subjects were of normal body mass index, euglycemic, and normolipemic.
  
  
  RESULTS
  The postmenopausal women were older (group 1, 43.1 +/- 5.0 vs groups 2 and 3, 57.9 +/- 7.4 years, P < 0.001 and 56.1 +/- 4.5 years, P < 0.001, respectively) and had lower serum estradiol levels (group 2, 22.2 +/- 3.2 vs group 1, 442.5 +/- 248.2 pmol/L, P < 0.05), which were restored to premenopausal levels with estrogen therapy. Expression analysis revealed that levels of transcripts encoding aromatase were greater in gluteal than abdominal depots in each group in postmenopausal versus premenopausal women (P < 0.05). Use of hormone therapy did not influence aromatase gene expression in either depot. No differences were detected in the expression of ER or AR between groups of between tissue depots.
  
  
  CONCLUSIONS
  Thus, the capacity of adipose tissue to produce estrogen seems to increase significantly with age at the time of menopause and to be unaltered by exogenous estrogen therapy. This difference in extragonadal estrogen production with age may play a pivotal role in the increase in estrogen-dependent malignancies in the postmenopausal years.
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Misso
authors.forename: Christina
authors.initials: C
authors.lastname: Jang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adams
authors.forename: Jane
authors.initials: J
authors.lastname: Tran
authors.forename: Yoko
authors.initials: Y
authors.lastname: Murata
authors.forename: Robin
authors.initials: R
authors.lastname: Bell
authors.forename: Wah Chin
authors.initials: WC
authors.lastname: Boon
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.forename: Susan R
authors.initials: SR
authors.lastname: Davis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D012313:RNA / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012313:RNA; D001141:Aromatase