Aromatase in Human Bone Tissue

Sasano, Hironobu; Uzuki, Miwa; Sawai, Takashi; Nishimura, Hiroshi; Matsunaga, Gen; Kashimoto, Osamu; Harada, Nobuhiro

doi:10.1359/jbmr.1997.12.9.1416

Cited by 241 publications

(143 citation statements)

References 38 publications

(64 reference statements)

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“…Several groups have shown that regulation of CYP19 gene expression is quite different in different tissues (12). The main promoters used are pII and I.3 in ovary, I.1 in placenta and I.4 in adipose stromal cells (10,22,23,46).…”

Section: Discussionmentioning

confidence: 99%

Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments

Enjuanes

Garcia-Giralt

Supervía

et al. 2003

European Journal of Endocrinology

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Objective: Extragonadal estrogen biosynthesis is relevant for the regulation of bone metabolism. The aims of this paper were: (i) to examine CYP19 (aromatase) gene expression in primary cultures of osteoblasts under several hormone and cytokine treatments and (ii) to study the promoter usage of CYP19 in these cells. Methods: Primary cultures of osteoblasts were obtained from healthy donors. The effects of vitamin D and other factors on CYP19 expression were analysed by semiquantitative RT-PCR. Furthermore, CYP19 alternative promoter usage under the different treatments was characterized by RT-PCR. Results: CYP19 transcripts were detected in cultured human osteoblasts in serum-free conditions. Vitamin D, dexamethasone, 17b-estradiol and testosterone increased transcript levels of CYP19, whereas interleukin-1b or tumor necrosis factor a decreased them. Aromatase mRNA produced under treatment with vitamin D was transcribed from promoters I.4 and I.3, while stimulation with dexamethasone or dexamethasone plus vitamin D also involved promoter I.2. Testosterone activated promoters I.2 and I.4. Conclusions: Our results suggested that vitamin D, testosterone, estrogens and glucocorticoids regulate CYP19 gene expression in human primary osteoblasts and the main promoter used appears to be promoter I.4. Promoters pII and I.3 seem to be related to basal transcription and may mediate estrogen stimulation, while promoter I.2 seems to play a role in the effect of glucocorticoids. These findings indicate that vitamin D and several hormones regulate local estrogen synthesis in human osteoblasts mainly through usage of promoters I.4 and I.3.

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Section: Discussionmentioning

confidence: 99%

Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments

Enjuanes

Garcia-Giralt

Supervía

et al. 2003

European Journal of Endocrinology

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“…Immunohistochemistry and in situ hybridization have revealed that aromatase (CYP19) is expressed in osteoblasts, osteocytes, lining cells, and chondrocytes (5). Aromatase (CYP19) is the rate-limiting enzyme of estrogen biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Forskolin and dexamethasone synergistically induce aromatase (CYP19) expression in the human osteoblastic cell line SV-HFO

Watanabe

Ohno²,

Nakajin³

2005

eur j endocrinol

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Objective: Recent progress supports the importance of local estrogen secretion in human bone tissues to increase and maintain bone mineral density. In a previous study, we reported that the expression of aromatase (CYP19) is dexamethasone (Dex)-dependent and oncostatin M (OSM) increases the expression synergistically with Dex. In the present study, we examined the effects of forskolin (FSK) as another potential synergistic factor. Results: Co-administration of 100 nM Dex and 10 mM FSK increased aromatase activity 4-fold compared with Dex alone. The results of reverse transcriptase (RT)-PCR suggest that the amount of CYP19 gene transcript was also up-regulated by FSK synergistically with Dex, and that promoter I.4, which is not activated by FSK alone, is activated by FSK synergistically with Dex. The results of RT-PCR also suggest that promoter II, which responds to FSK, was not activated even in the presence of FSK in SV-HFO. The promoter I.4 sequence that was transfected into SV-HFO was activated by FSK synergistically with Dex. Conclusions: Synergistic up-regulation of aromatase activity, CYP19 gene transcript, and promoter I.4 activity were Dex-dependent and not up-regulated by FSK alone. The results of this work may form the basis of bone-specific estrogen-replacement therapy that increases the estrogen concentration in bone tissue only.

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“…In situ hybridization and immunohistochemistry have shown that aromatase immunoreactivity and gene transcripts are localized in lining cells, osteoblasts and chondrocytes of human bone tissue (Sasano et al 1997, Oz et al 2001. Some types of osteoclasts also express aromatase immunoreactivity (Oz et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…1). RT-PCR analysis indicates that the most dominant 5 UTR in aromatase gene transcript in human bone tissue is derived from upstream exon I.4 (Sasano et al 1997, Shozu & Simpson 1998). This suggests that the 5 region of exon I.4 (promoter I.4) is predominantly used in bone tissue to drive aromatase expression.…”

Section: Introductionmentioning

confidence: 99%

Aromatase expression in the human fetal osteoblastic cell line SV-HFO

Watanabe

Simpson

Pathirage

et al. 2004

Journal of Molecular Endocrinology

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A number of clinical studies have highlighted the importance of estrogen in bone growth and maintenance in men and postmenopausal women. In these instances, estrogen is synthesized locally within bone tissue by aromatase, encoded by the CYP19 gene. The mechanisms regulating aromatase expression in bone, however, are unclear. In this work we characterized the expression of aromatase activity and gene transcripts in the human fetal osteoblastic cell line, SV-HFO. Aromatase activity and gene transcript expression were stimulated by dexamethasone. Oncostatin M strongly stimulated aromatase expression in synergy with dexamethasone. These factors induced CYP19 transcripts that included the sequence of exon I.4 in their 5′UTR. Consistent with this, a reporter construct harboring the genomic sequence of the promoter region of exon I.4 (promoter I.4) was also activated by dexamethasone and oncostatin M. 5′ deletion and mutation analysis revealed important roles for a glucocorticoid response element, an interferon activating sequence and a putative binding site for Sp1. Transfection of exogenous glucocorticoid receptor, STAT3 or Sp1 increased promoter activity, indicating a potential role for these transcription factors in regulating aromatase expression in SV-HFO cells. These data suggest that the SV-HFO cell line is a valuable model with which to elucidate the mechanisms regulating local estrogen synthesis in osteoblasts.

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Aromatase in Human Bone Tissue

Cited by 241 publications

References 38 publications

Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments

Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments

Forskolin and dexamethasone synergistically induce aromatase (CYP19) expression in the human osteoblastic cell line SV-HFO

Aromatase expression in the human fetal osteoblastic cell line SV-HFO

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