Stanozolol regulates proliferation of growth plate chondrocytes via activation of ERalpha in GnRHa-treated adolescent rats

J Pediatr Endocrinol Metab. 2011;24(5-6):275-81. doi: 10.1515/jpem.2011.183.

Abstract

Improving the final adult height is one of the most important aims for treatment of central precocious puberty. Stanozolol (ST) is a synthetic derivative of androgen. In this study, we investigated the effects and the mechanisms of ST on the proliferation of growth plate chondrocytes isolated from adolescent rats treated with gonadotropin-releasing hormone analogue (GnRHa). Treatment with ST resulted in time- and concentration-dependent effects on proliferation as determined by MTT and proliferating cell nuclear antigen (PCNA) assays. Western blotting showed that ST increased the phosphorylation level of the estrogen receptor alpha (ERalpha), but not the androgen receptor (AR). Pharmacological inhibition of ERalpha and mitogen-activated protein kinase (MAPK) attenuated the effects of ST on the proliferation of growth plate chondrocytes. A molecular dynamics simulation showed hydrophobic interactions between ST and ERalpha. These results suggested that ERalpha, but not AR, partially mediates the ST-driven proliferation of growth plate chondrocytes, and that multiple pathways may be involved in the mechanism of action of ST.

MeSH terms

  • Animals
  • Binding Sites
  • Body Height / drug effects
  • Cell Proliferation / drug effects
  • Child
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Disease Models, Animal
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / pharmacology
  • Growth Plate / cytology
  • Growth Plate / drug effects
  • Growth Plate / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Male
  • Molecular Dynamics Simulation
  • Phosphorylation
  • Puberty, Precocious / drug therapy
  • Puberty, Precocious / metabolism
  • Puberty, Precocious / pathology
  • Rats
  • Receptors, Androgen / metabolism
  • Stanozolol / chemistry
  • Stanozolol / pharmacology*

Substances

  • Estrogen Receptor alpha
  • Receptors, Androgen
  • Gonadotropin-Releasing Hormone
  • Stanozolol
  • LHRH, Ala(6)-Gly(10)-ethylamide-