Aromatase in aging women

S E Bulun, Bulun Se, Zeitoun K, K Zeitoun, Sasano H, H Sasano, Simpson ER, E R Simpson
Seminars in reproductive endocrinology · 1999 · doi:10.1055/s-2007-1016244 · PMID:10851574
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⚙ AI-generated summary by claude@2026-06, 2026-06-12 ⓘ

Aromatase converts steroids to estrogens in various tissues, with its expression in adipose and skin increasing with age and body weight, impacting bone, uterine health, and potentially brain function.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-05 · read from full text ⓘ

This review discusses how aromatase, which converts C19 steroids to estrogens, contributes to estrogen production during the climacteric by driving extraglandular (peripheral) estrogen biosynthesis in tissues such as adipose and skin, with expression that increases with body weight and advancing age. It links increased aromatase-driven estradiol/estrone production to consequences including uterine bleeding, endometrial hyperplasia and cancer, and to the slowing of postmenopausal bone loss, while also noting that excessive or inappropriate aromatase expression has been observed in adipose fibroblasts around breast carcinoma, endometriosis-derived stromal cells, and stromal cells in endometrial cancer, leading to higher local estrogen concentrations. The paper emphasizes that aromatase regulation is complex due to alternatively used promoters whose activity can be altered by hormones and by factors such as prostaglandin E2 versus glucocorticoids plus cytokines, including promoter switching influenced by breast cancer presence. This paper is centrally about endometriosis via its cited demonstration of elevated aromatase expression in endometriosis-derived stromal cells and the resulting increased local estrogen levels that promote steroid-responsive tissue growth.

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Abstract

Cessation of ovarian estrogen secretion is the key event during the climacteric. An enzyme termed aromatase in a number of human tissues and cells, including ovarian granulosa cells, the placental syncytiotrophoblast, adipose and skin fibroblasts, bone, and the brain, catalyzes the conversion of C19 steroids to estrogens. Aromatase expression in adipose tissue and possibly the skin primarily accounts for the extraglandular (peripheral) formation of estrogen and increases as a function of body weight and advancing age. Sufficient circulating levels of the biologically active estrogen, estradiol, can be produced as a result of extraglandular aromatization of androstenedione to estrone, which is subsequently reduced to estradiol in peripheral tissues, to cause uterine bleeding and endometrial hyperplasia and cancer in obese anovulatory or postmenopausal women. Extraglandular aromatase expression in adipose tissue and skin (via increasing circulating levels of estradiol) and bone (via increasing local estrogen concentrations) is of paramount importance in slowing the rate of postmenopausal bone loss. Moreover, excessive or inappropriate aromatase expression was demonstrated in adipose fibroblasts surrounding a breast carcinoma, endometriosis-derived stromal cells, and stromal cells in endometrial cancer and gave rise to increased local estrogen concentrations in these tissues. Whether systemically delivered or locally produced, elevated estrogen levels promote the growth of these steroid-responsive tissues. Finally, local estrogen biosynthesis by aromatase activity in the brain may be important in the regulation of various cognitive and hypothalamic functions. The regulation of aromatase expression in human cells via alternatively used promoters, which can be activated or inhibited by various hormones, increases the complexity of estrogen biosynthesis in the human body. Aromatase expression is under the control of the classically located proximal promoter II in the ovary and a far distal promoter I.1 (40 kb upstream of the translation initiation site) in the placenta. In adipose tissue, two other promoters (I.4 and I.3) located between I.1 and II are used in addition to the ovarian-type promoter II. To add a further twist, promoter use in adipose fibroblasts switches between promoters II/I.3 and I.4 upon treatment of these cells with prostaglandin E2 (PGE2) versus glucocorticoids plus cytokines. Moreover, the presence of a carcinoma in breast adipose tissue causes a switch of promoter use from I.4 to II/I.3. Molecular and cellular mechanisms responsible for estrogen formation and their physiologic and clinical relevance will be reviewed in this article.
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Abstract

Cessation of ovarian estrogen secretion is the key event during the climacteric. An enzyme termed aromatase in a number of human tissues and cells, including ovarian granulosa cells, the placental syncytiotrophoblast, adipose and skin fibroblasts, bone, and the brain, catalyzes the conversion of C19 steroids to estrogens. Aromatase expression in adipose tissue and possibly the skin primarily accounts for the extraglandular (peripheral) formation of estrogen and increases as a function of body weight and advancing age. Sufficient circulating levels of the biologically active estrogen, estradiol, can be produced as a result of extraglandular aromatization of androstenedione to estrone, which is subsequently reduced to estradiol in peripheral tissues, to cause uterine bleeding and endometrial hyperplasia and cancer in obese anovulatory or postmenopausal women. Extraglandular aromatase expression in adipose tissue and skin (via increasing circulating levels of estradiol) and bone (via increasing local estrogen concentrations) is of paramount importance in slowing the rate of postmenopausal bone loss. Moreover, excessive or inappropriate aromatase expression was demonstrated in adipose fibroblasts surrounding a breast carcinoma, endometriosis-derived stromal cells, and stromal cells in endometrial cancer and gave rise to increased local estrogen concentrations in these tissues. Whether systemically delivered or locally produced, elevated estrogen levels promote the growth of these steroid-responsive tissues. Finally, local estrogen biosynthesis by aromatase activity in the brain may be important in the regulation of various cognitive and hypothalamic functions. The regulation of aromatase expression in human cells via alternatively used promoters, which can be activated or inhibited by various hormones, increases the complexity of estrogen biosynthesis in the human body. Aromatase expression is under the control of the classically located proximal promoter II in the Ovary and a far distal promoter I.1 (40 kb upstream of the translation initiation site) in the placenta. In adipose tissue, two other promoters (I.4 and I.3) located between I.1 and II are used in addition to the ovarian-type promoter II. To add a further twist, promoter use in adipose fibroblasts switches between promoters II/I.3 and I.4 upon treatment of these cells with prostaglandin E2 (PGE2) versus glucocorticoids plus cytokines. Moreover, the presence of a carcinoma in breast adipose tissue causes a switch of promoter use from I.4 to II/I.3. Molecular and cellular mechanisms responsible for estrogen formation and their physiologic and clinical relevance will be reviewed in this article.

Keywords

Aromatase - estrogen - steroidogenesis - adipose tissue - aging - breast cancer - osteoporosis - endometriosis - endometrial cancer - brain - bone - skin

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Condition tags

endometriosis

MeSH descriptors

Adipose Tissue Aging Aromatase Breast Neoplasms Adipose Tissue Aged Aging Aromatase Aromatase Bone and Bones Bone and Bones Breast Neoplasms Breast Neoplasms Climacteric Climacteric Dinoprostone Dinoprostone Estrogens Estrogens Female

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europepmc
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pubmed
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