Two different pathways for the maintenance of trabecular bone in adult male mice

Marie K. Lindberg, Sofia MovéRare, Stanko Skrtic, Sari Alatalo, Jussi Halleen, Subburaman Mohan, J. Gustafsson, Claes Ohlsson

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Androgens may regulate the male skeleton either directly via activation of the androgen receptor (AR) or indirectly via aromatization of androgens into estrogen and, thereafter, via activation of estrogen receptors (ERs). There are two known estrogen receptors, ER-α and ER-β. The aim of this study was to investigate the relative roles of ER-α, ER-β, and AR in the maintenance of trabecular bone in male mice. Seven-month-old male mice, lacking ER-α (ERKO), ER-β (BERKO), or both receptors (DERKO), were orchidectomized (orx) and treated for 3 weeks with 0.7 μg/mouse per day of 17β-estradiol or vehicle. No reduction in trabecular bone mineral density (BMD) was seen in ERKO, BERKO, or DERKO mice before orx, showing that neither ER-α nor ER-β is required for the maintenance of a normal trabecular BMD in male mice. After orx, there was a pronounced decrease in trabecular BMD, similar for all groups, resulting in equal levels of trabecular BMD in all genotypes. This reduction was reversed completely in wild-type (WT) and BERKO mice treated with estrogen, and no significant effect of estrogen was found in ERKO or DERKO mice. In summary, the trabecular bone is preserved both by a testicular factor, presumably testosterone acting via AR and by an estrogen-induced activation of ER-α. These results indicate that AR and ER-α are redundant in the maintenance of the trabecular bone in male mice. In contrast, ER-β is of no importance for the regulation of trabecular bone in male mice.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalJournal of Bone and Mineral Research
Volume17
Issue number4
DOIs
StatePublished - Jan 1 2002

Keywords

  • Androgens
  • Bone
  • Estrogen receptors
  • Males
  • Transgenic

ASJC Scopus subject areas

  • Surgery

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