Effects of fenoterol on the skeletal system depend on the androgen level

Pharmacol Rep. 2017 Apr;69(2):260-267. doi: 10.1016/j.pharep.2016.09.023. Epub 2016 Sep 29.

Abstract

Background: The role of sympathetic nervous system in the osseous tissue remodeling is not clear enough.

Methods: The effects of fenoterol, a selective β2-adrenomimetic drug, on the skeletal system of normal and androgen deficient (orchidectomized) rats were studied in vivo. Osteoclastogenesis and mRNA expression in osteoblasts were investigated in vitro in mouse cell cultures.

Results: Fenoterol administered to animals with physiological androgen level unfavorably affected the skeletal system, damaging the bone microarchitecture. Androgen deficiency induced osteoporotic changes, and fenoterol protected the osseous tissue from consequences of androgen deficiency. The results of in vitro studies correlated with the in vivo observations. A significantly increased number of osteoclasts in bone marrow cell cultures to which testosterone and fenoterol were added simultaneously was demonstrated. In cultures without the addition of testosterone, fenoterol significantly inhibited osteoclastogenesis in comparison with control cultures.

Conclusions: The results indicate the favorable action of fenoterol in conditions of testosterone deficiency, and its destructive influence upon the skeleton in the presence of androgens. The results confirm the key role of sympathetic nervous system in the regulation of bone remodeling.

Keywords: Androgens; Bone; Fenoterol; Osteoblasts; Osteoclasts.

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Bone Resorption / drug therapy
  • Bone Resorption / metabolism
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Fenoterol / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orchiectomy / methods
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Testosterone / metabolism

Substances

  • Androgens
  • RNA, Messenger
  • Fenoterol
  • Testosterone