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. DESIGN: 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. CONCLUSION: 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.
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. DESIGN: 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. CONCLUSION: 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: Gail A Laughlin; Joachim H Ix; Kevin Cummins; Matthew A Allison; Lori B Daniels Journal: Clin Endocrinol (Oxf) Date: 2012-09 Impact factor: 3.478
Authors: Susan R Davis; Robin J Bell; Penelope J Robinson; David J Handelsman; Tom Gilbert; James Phung; Reena Desai; Jessica E Lockery; Robyn L Woods; Rory S Wolfe; Christopher M Reid; Mark R Nelson; Anne M Murray; John J McNeil Journal: J Clin Endocrinol Metab Date: 2019-12-01 Impact factor: 5.958
Authors: Laurivette Mosquera; Luz Shepherd; Aranza I Torrado; Yvonne M Torres-Diaz; Jorge D Miranda; Annabell C Segarra Journal: J Vet Sci Technol Date: 2015-11-30
Authors: Roni T Falk; Elisabet Gentzschein; Frank Z Stanczyk; Louise A Brinton; Montserrat Garcia-Closas; Olga B Ioffe; Mark E Sherman Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-08 Impact factor: 4.254
Authors: Therése Andersson; Kotryna Simonyte; Ruth Andrew; Magnus Strand; Jonas Burén; Brian R Walker; Cecilia Mattsson; Tommy Olsson Journal: PLoS One Date: 2009-12-29 Impact factor: 3.240