Mechanisms in tissue-specific regulation of estrogen biosynthesis in humans

Kamat, Amrita; Hinshelwood, Margaret M.; Murry, Barbara A.; Mendelson, Carole R.

doi:10.1016/s1043-2760(02)00567-2

Cited by 198 publications

(143 citation statements)

References 58 publications

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“…Much attention has been given to the regulation of the aromatase gene and its implication in the development and progression of human diseases. Several excellent reviews in this area have been recently published [3][4][5]. The present review focuses on the molecular, cellular, and normal physiological mechanisms regulating the expression of the aromatase gene in the ovary with a particular emphasis on the rat.…”

Section: Introductionmentioning

confidence: 99%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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Summary-Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene, which contains an unusually large regulatory region. In most mammals, aromatase expression is under the control of two distinct promoters a gonad-and a brain-specific promoter. In humans, this gene contains 10 tissue-specific promoters that are alternatively used in various cell types and tumors. Each promoter is regulated by a distinct set of regulatory sequences and transcription factors that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to be the primary signaling cascade through which the gonad Cyp19 promoter is regulated. Very interestingly, in rat luteal cells, the proximal promoter is not controlled in a cAMP dependent manner. Strikingly, these cells express aromatase at high levels similar to those found in preovulatory follicles, suggesting that alternative and powerful mechanisms control aromatase expression in luteal cells and that the rat corpus luteum represents an important paradigm for understanding alternative controls of the aromatase gene. Here, the molecular and cellular mechanisms controlling the expression of the aromatase gene in granulosa and luteal cells are discussed.

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Section: Introductionmentioning

confidence: 99%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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“…In fact, adipose and other tissues express aromatase, the product of the CYP19 gene, a critical enzyme in the peripheral synthesis of estrogens. It is responsible for catalysing the aromatization of C19 androgens to C18 estrogens such as estradiol and estrone (2,3). Estrone is the most abundant estrogen in the serum of postmenopausal women.…”

Section: Introductionmentioning

confidence: 99%

A common polymorphism in the 5'-untranslated region of the aromatase gene influences bone mass and fracture risk

Zarrabeitia

Hernández

Valero

et al. 2004

European Journal of Endocrinology

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Objective: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5 0 -untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). Design: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. Methods: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. Results: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P ¼ 0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. Conclusions: A common biallelic polymorphism in the 5 0 -untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.European Journal of Endocrinology 150 699-704

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“…Tissue-specific regulation of the human aromatase P450 (CYP19) gene expression is a key step in controlling the local and circulating levels of estrogen and the diverse physiological impacts of the hormone on different parts of the body (Kamat et al, 2002;Simpson et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element

Ghosh

et al. 2005

Oncogene

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Mechanisms in tissue-specific regulation of estrogen biosynthesis in humans

Cited by 198 publications

References 58 publications

Aromatase expression in the ovary: Hormonal and molecular regulation

Aromatase expression in the ovary: Hormonal and molecular regulation

A common polymorphism in the 5'-untranslated region of the aromatase gene influences bone mass and fracture risk

Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element

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