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

Shun-Ye Zhu, Yan-Hong Li 1 , Hua-Mei Ma 1 , Ting-Ting Huang 3 , Hai-Bin Luo 4 , Juan Dou 2 ,  and Min-Lian Du 1
  • 1 Department of Pediatrics, the First Affiliated Hospital of SUN Yat-Sen University, Guangzhou 510080, P.R. China
  • 2 Department of Pediatrics, the Third Affiliated Hospital of SUN Yat-Sen University, Guangzhou 510630, P.R. China
  • 3 Department of Pediatrics, University of Miami School of Medicine, Miami, FL 33156, USA
  • 4 School of Pharmaceutical Sciences, SUN Yat-SenUniversity, Guangzhou 510080, P.R. China

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 α (ERα), but not the androgen receptor (AR). Pharmacological inhibition of ERα 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 ERα. These results suggested that ERα, 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.

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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.

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