Article

Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy.

Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Menopause (impact factor: 3.76). 04/2005; 12(2):210-5. pp.210-5
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

Circulating C19 steroid precursors
 
endometrial cancer
 
estrogen therapy
 
estrogen-dependent malignancies
 
estrogen-related cancers
 
exogenous estrogen therapy
 
extragonadal estrogen production
 
extragonadal estrogen synthesis
 
gluteal fat
 
group 3
 
hormone therapy
 
lower serum estradiol levels
 
natural menopause
 
normal body mass index
 
ovarian estrogen production
 
postmenopausal estrogen production
 
postmenopausal estrogen therapy
 
postmenopausal years
 
premenopausal levels
 
subcutaneous abdominal