Steroid hormone metabolizing enzymes in benign and malignant human bone tumors

Abstract

Importance in the field: Primary bone tumors are considered as (sex steroid) hormone-dependent tumors. Osteosarcoma, osteoblastoma and bone cysts are preferentially found in males, while giant cell tumors are more common in females. Indeed, bone tumor development and progression are influenced by sex steroid hormones derived from in situ synthesis in bone cells.

Areas covered in this review: This review describes intracrine mechanisms for local formation of the biologically most active estrogen, 17β-estradiol (E2), from circulating steroid precursors through the ‘aromatase’ (aromatization of androgens) and the ‘sulfatase’ (conversion of inactive estrone-sulfate) pathway.

What the reader will gain: The reader gains knowledge on both pathways and the enzymes, which contribute to the in situ availability of active hormones, namely 3β-hydroxysteroid dehydrogenases, 17β-hydroxysteroid dehydrogenases, aromatase, steroid sulfatases and sulfotransferases. An overview is given and the expression and function of these enzymes in bone tumors are discussed.

Take home message: Knowledge on pathways for the in situ formation of E2 in bone cells may allow the identification of potential targets for i) novel endocrine therapeutic options in primary bone tumors and ii) future preventive interventions.

Keywords::

• aromatase
• bone tumors
• estrogen
• estrogen sulfotransferase
• giant cell tumors
• intracrine
• osteosarcoma
• sex steroid hormones
• steroid dehydrogenase
• steroid sulfatase

Acknowledgements

M Svoboda and T Thalhammer acknowledge support by the OVCAD Strep Project FA751C0203.

Notes

This box summarizes key points contained in the article.