Regulation of Aromatase Expression in Estrogen-Responsive Breast and Uterine Disease: From Bench to Treatment

Bulun, Serdar E.; Lin, Zhihong; İmir, Gonca; Amin, Sanober; Demura, Masashi; Yılmaz, Bertan; Martin, Regina Matsunaga; Utsunomiya, Hiroki; Thung, Steven; Gürateş, Bilgin; Tamura, Mitsutoshi; Langoi, David; Deb, Sanjukta

doi:10.1124/pr.57.3.6

Cited by 470 publications

(485 citation statements)

References 174 publications

Supporting

Mentioning

469

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

View full text Add to dashboard Cite

show abstract

“…Because its overall homology to other members of the P-450 superfamily is low, aromatase belongs to a separate gene family designated CYP19 (Santen and Harvey, 1999). Regulation of aromatase expression in human tissues is quite complex, involving alternative promoter sites that provide tissue-specific control (Bulun et al, 2005;Chen et al, 2009). In normal breast, the mammary adipose tissue maintains low levels of aromatase expression almost exclusively through promoter I.4, which is regulated by the combined action of a glucocorticoid and a member of the class I cytokine family (interleukin 6, 11).…”

mentioning

confidence: 99%

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells. METHODS: Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT -PCR. PGE 2 and cAMP were measured by kits. RESULTS: Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE 2 production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression. CONCLUSIONS: This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression.

show abstract

“…In this subset it is possible that a greater proportion of androgens are converted into estrogens, which would explain the increased oncogenic risk. Nevertheless, there is as yet no consensus in the literature with relation to these findings, since some epidemiological studies have demonstrated an increased risk whereas others did not detect this association 13 . Notwithstanding, it is recommended that women taking androgens should be monitored for cancer of the endometrium or breasts, following the same recommendations as for conventional hormone treatment.…”

Section: The Reviewmentioning

confidence: 79%

“…Although no androgens have been approved by the FDA (Food profile, altered liver function and, more rarely, changes in the pitch of voice, clitoromegaly and virilization of female fetuses if pregnancy occurs during treatment 13 . However, with appropriate doses of 300 mcg of testosterone per day, such effects are reported rarely.…”

Section: The Reviewmentioning

confidence: 99%

Deficiência androgênica na mulher

Fonseca¹,

Scapinelli²,

Aoki³

et al. 2010

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

The evidence suggest that androgen deficiency in women induces sexual dysfunction as its main clinical manifestation, in particular reduced libido. However, other factors may be involved in the genesis of this disease, such as interpersonal relationships, social stressors, physical inactivity and the partner. The prevalence of sexual problems among women ranges from 9 to 43% and, recently, many studies have reported that androgens are beneficial not only for women's sexual function, but also for mood disorders and vasomotor symptoms. This is why physicians should include androgen deficiency syndrome in their differential diagnosis, even in women with adequate estrogen levels. Our objective was to present the practical aspects of this disease, emphasizing diagnosis and focusing on treatment. This review searched PUBMED for publications from the last 51 years, up to May 2010, including consensus statements and expert opinions and identified 105 articles. We concluded that the androgen deficiency syndrome in women is overlooked in clinical practice. There is no consensus in the literature regarding diagnosis or treatment, including choice of drug, route of administration and time of application.

show abstract

Regulation of Aromatase Expression in Estrogen-Responsive Breast and Uterine Disease: From Bench to Treatment

Cited by 470 publications

References 174 publications

Aromatase expression in the ovary: Hormonal and molecular regulation

Aromatase expression in the ovary: Hormonal and molecular regulation

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

Deficiência androgênica na mulher

Contact Info

Product

Resources

About