Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats

Katsuji Aizawa, Motoyuki Iemitsu, Seiji Maeda, Subrina Jesmin, Takeshi Otsuki, Chishimba N. Mowa, Takashi Miyauchi, Noboru Mesaki

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

The functional importance of sex steroid hormones (testosterone and estrogens), derived from extragonadal tissues, has recently gained significant appreciation. Circulating dehydroepiandrosterone (DHEA) is peripherally taken up and converted to testosterone by 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, and testosterone in turn is irreversibly converted to estrogens by aromatase cytochrome P-450 (P450arom). Although sex steroid hormones have been implicated in skeletal muscle regulation and adaptation, it is unclear whether skeletal muscles have a local steroidogenic enzymatic machinery capable of metabolizing circulating DHEA. Thus, here, we investigate whether the three key steroidogenic enzymes (3β-HSD, 17β-HSD, and P450arom) are present in the skeletal muscle and are capable of generating sex steroid hormones. Consistent with our hypothesis, the present study demonstrates mRNA and protein expression of these enzymes in the skeletal muscle cells of rats both in vivo and in culture (in vitro). Importantly, we also show an intracellular formation of testosterone and estradiol from DHEA or testosterone in cultured muscle cells in a dose-dependent manner. These findings are novel and important in that they provide the first evidence showing that skeletal muscles are capable of locally synthesizing sex steroid hormones from circulating DHEA or testosterone.

Original languageEnglish
Pages (from-to)E577-E584
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number2
DOIs
Publication statusPublished - 2007 Feb
Externally publishedYes

Keywords

  • 17β-hydroxysteroid dehydrogenase
  • 3β-hydroxysteroid dehydrogenase
  • Androgen
  • Aromatase cytochrome P-450
  • Dehydroepiandrosterone
  • Estrogen

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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