Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer

Abstract

Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E₁) was the predominant estrogen in premenopausal breast adipose tissue, and E₁ and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E₂) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E₁ (1519 vs. 3244, p < .05) and E₂ (404 vs. 889 pmol/kg, p < .05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05–0.07 vs. 0.17; 0.03–0.2, p = .010) and CYP19A1 (0.08; 0.07–0.14 vs. 0.22; 0.09–0.54, p = .025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E₁ and E₂ concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer.

摘要

血液循环中雌激素在月经周期中波动, 但这种波动是否与脂肪组织中的局部激素水平有关尚不清楚。我们分析了雌激素受体阳性乳腺癌（n=11）和非乳腺癌（n=17）的绝经前女性乳房皮下脂肪组织中雌激素浓度和雌激素调节酶的基因表达。雌酮（E1）是绝经前乳腺脂肪组织中主要的雌激素, 脂肪组织中E1和CYP19A1的mRNA表达与BMI呈正相关。脂肪组织中雌二醇（E2）浓度在月经周期中波动, 与血清浓度相似。乳腺癌女性脂肪组织中E1（1519 vs. 3244, p<.05）和E2（404 vs. 889 pmol/kg, p<.05）水平在卵泡期低于黄体期, 而在对照组女性中无显著差异。在卵泡期, HSD17B1的mRNA表达（中位数0.06；四分位数间距0.05-0.07 vs. 0.17；0.03-0.2, p=.010）和CYP19A1的mRNA表达 (0.08；0.07 - 0.14 vs. 0.22；0.09-0.54, p=.025)在乳腺癌患者中低于对照组。总之, 在月经周期中, 脂肪组织中E1和E2浓度的变化以及雌激素调节CYP19A1和HSD17B1的变化可能与乳腺癌女性局部雌激素代谢紊乱有关。

Keywords:

• Adipose tissue
• aromatase
• breast cancer
• estrogen
• menstrual cycle

Acknowledgements

We thank Päivi Ihamuotila and Kirsti Räsänen for their expert technical assistance.

Disclosure statement

H.S-P. has been a speaker for Mylan and received funding for congress trips from Mylan and MSD. T.M. has been a speaker and/or received consulting fees from Mylan and Novo Nordisk. The remaining authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the under grant Jane and Aatos Erkko Foundation, under grant Folkhälsan Research Center, under grant Sigrid Jusélius Foundation, under grant Päivikki and Sakari Sohlberg Foundation, and under grant State funding for university-level health research.