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

Abstract

Improving the fi nal 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 (ER α ), but not the androgen receptor (AR). Pharmacological inhibition of ER α 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 ER α . These results suggested that ER α , 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.

Clinical Evaluation of Intra-articular Administration of Stanozolol to Manage Lameness Associated With Acute and Chronic Osteoarthritis in Horses

“…Its properties include anabolic and/or androgenic activity [9], probably associated with its affinity for androgenic and, at lower doses, glucocorticoid receptors [10]. It has been demonstrated that stanozolol induces in vitro upregulation of osteoblast proliferation, collagen synthesis through transforming growth factor-b1 activity [11], chondrocyte secretion of insulin-like growth factor-1 [12], and, in rats, growth plate chondrocyte proliferation [13]. Moreover, it reduces NO production [12].…”

GnRHa/Stanozolol Combined Therapy Maintains Normal Bone Growth in Central Precocious Puberty

“…Previous studies reveal that it stimulates a height velocity increase without bone age progression in patients with Turner syndrome undergoing oxandrolone treatment (19). Our previous study also showed that ST promotes the proliferation of growth plate chondrocytes (15). Therefore, we speculated that ST stimulates growth plate development through the promotion of chondrogenic differentiation in patients who were experiencing an inhibitory effect of GnRHa.…”

“…Rats were euthanized at 7 weeks of age. Hind limb specimens were dissected and fixed in 4% paraformaldehyde for histological analyses (n = 5 animals per group) ( 15 ).…”

“…Patients with TS who were treated with oxandrolone, height velocity was increased without bone age progression ( 19 ). Moreover, our previous study shows that ST promotes proliferation of growth plate chondrocytes ( 15 ). Together, these studies indicate that anabolic steroid hormones may promote long bone growth without increasing bone age to achieve the final adult height.…”

“…A few studies have assessed the effect of GH administration on the height of patients with CPP, and some show a positive effect of GH/GnRHa therapy in children with decreased growth during GnRHa therapy ( 13 , 14 ). However, there are some disadvantages of GH treatment: its cost is high and its application is inconvenient ( 15 ). Other treatments such as estrogen mini-dose replacement, to overcome the decreased growth plate development that is induced by GnRHa, have been reported ( 16 ).…”