Journal of the American Academy of Dermatology
Estrogen production and action☆,☆☆,★,★★
Section snippets
Aromatase expression in adipose tissue
Hemsell et al8 first addressed the significance of human adipose tissue as a major source of estrogen production and demonstrated that in both women and men with advancing age, there is a progressive increase in the efficiency with which circulating androstenedione is converted to estrone. The authors and others27, 28 have subsequently shown that this age-related elevation of peripheral estrogen formation is associated with increases in both aromatase activity and mRNA levels in the adipose
Aromatase expression in skin
Aromatase expression in skin fibroblasts might account for a significant portion of peripheral estrogen formation in postmenopausal women. The relationship between peripheral aromatization and body weight is highly suggestive of a significant role of adipose tissue in this process. However, an increase in weight results in an increase of body surface area; thus it is very difficult to accurately estimate the relative contributions of skin and adipose tissue on extraglandular estrogen formation.
Aromatase expression in bone
It is tempting to speculate that postmenopausal bone loss may be modified by levels of local aromatase activity in bone. In fact, aromatase expression has been demonstrated in osteoblasts and chondrocytes from both fetal and adult bone tissues.15, 16 Conversely, another group of investigators45 failed to demonstrate aromatase mRNA in normal bone tissue from the femoral neck. Aromatase expression in cultured osteoblastic cells seems to be regulated by glucocorticoids and cytokines primarily via
Aromatase expression in brain
Several recent studies12 suggest estrogen replacement in postmenopausal women improves cognition, reduces the risk of developing dementia, and reduces the severity of existing dementia. This raises a question as to the significance of local estrogen formation because aromatase is expressed in many regions of the brain.9, 11, 48 Aromatase expression in brain tissue of birds and rodents regulates the activation of sexual behavior.9, 13, 14 Although aromatase is expressed in many sites and cell
Aromatase deficiency states
Until the 1990s, aromatase deficiency was considered incompatible with life; this belief may have inhibited the investigation of this diagnosis in suspected cases. After the first description in 1991 of a Japanese newborn girl with an aromatase P450 (P450arom) gene defect,50, 51 there have been several recent reports in world literature describing aromatase deficiency.3, 50, 52, 53, 54 Convincingly, estrogen biosynthesis in all these patients was virtually absent, giving rise to a number of
Estrogen receptors
Estrogen action in most tissues is mediated through the estrogen receptor (ER), a member of a large superfamily of nuclear receptors that function as ligand-activated transcription factors.60 These receptor proteins share a common structural and functional organization, with distinct domains that are responsible for ligand binding, DNA binding, and transcriptional activation. There are 2 forms of the ER that have been identified: the initially cloned ERα and the more recently cloned ERβ.61 In
Summary
Aromatase is a key enzyme for estrogen formation in human tissues. In women of reproductive age, the ovarian granulosa cells are important sites of estrogen formation for local use within the ovary as well as for endocrine signaling to a host of tissues, including the uterus, skin appendages, brain, bone, vascular system, and breast. However, there is an increasing awareness of the importance of local production of estrogens from precursor androgens within these target tissues themselves. This
Acknowledgements
We thank Margarita Guerrero for her expert editorial assistance.
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This article is part of a supplement whose publication was supported by an unrestricted educational grant from Pharmacia Consumer Healthcare.
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Supported in part by National Institutes of Health grants CA67167 and HD37108 and USAMRMC grant DAMD17-97-1-7025 (to S. E. B.).
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Disclosure: The authors attest that they have no conflicts of interest to disclose.
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Reprint requests: Linda R. Nelson, MD, PhD, Department of Obstetrics-Gynecology, University of Illinois at Chicago, 820 S Wood St, M/C 808, Chicago, IL 60612. E-mail: [email protected].