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

Abstract

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.

Association of CYP19 Gene Polymorphism with Vertebral Fractures in Japanese Postmenopausal Women

“…It is possible that local E 2 concentrations are more important in local tissues rather than serum levels. Bone cells are able to express aromatase and other enzymes required for estrogen synthesis locally (Janssen et al 1999;Shouzu and Simpson 1998;Watanabe et al 2004), and aromatase activity in cultured osteoblasts is quantitatively similar to that in adipose stromal cells (Shouzu and Simpson 1998). Thus, estrogen synthesized in bone cells might be important in postmenopausal bone metabolism.…”

Identification of an Aromatase Haplotype That Is Associated with Gene Expression and Postmenopausal Osteoporosis

“…Searching the TRANSFAC database of transcription factor binding sites by using an adipocyte-specific profile revealed potential binding sites for transcription factors such as specificity protein-1 (Sp1) and CCAAT/enhancer-binding protein (C/EBP) in the vicinity of the loci rs1062033 and rs767199. Those factors have been shown to modulate aromatase gene expression in some tissues (39,40). However, it is unclear to us whether those potential binding sites are actually functional.…”

Aromatase Activity and Bone Loss in Men

“…In the skeleton, the majority of aromatase transcripts contain exon 1.4 and exon 1.6 [31–33]. Some minor transcripts by promoter I.3, PII and If have been also described [31].…”