EFFECT OF TESTOSTERONE ON BONE MINERAL DENSITY (BMD) IN GROWTH HORMONE (GH) DEFICIENT RATS

Abstract

The contribution of GH and sex steroids to attainment of peak bone mass are not clear and require longitudinal studies. We are examining the interactions between testosterone and GH on BMD using the GH deficient and GH sufficient rat models (Lewis strain). In the first part of study, forty male GH deficient rats were included with half the rats castrated at age 4 weeks and half remained as controls. All rats received identical diet and housing. BMD of total body, femur and lumbar spine (L1-L4) were measured from early adulthood at age 12 and 36 weeks, using Dual Energy X-ray Absorptiometry (DEXA, LUNAR) equipped with special software for small animals. This DEXA software was validated for small animals prior to the study. There was strong agreement between bone mineral content and ash weight for total body (r2=0.90) and femur (r2=0.83) in 17 rats with weight ranging from 146 to 212 grams. At age 12 weeks, there was no difference in total body, femur and L1-L4 BMD between two groups. However at 36 weeks, the castrated rats had significantly lower L1-L4 BMD compared to the controls (data not shown). From age 12 to 36 weeks, rats of both groups had significant increase in total body and femur BMD (left). The castrated group had no increase in L1-L4 BMD, which is significantly different from the control rats. We conclude that testosterone, even in the presence of GH deficiency, is critical for maintaining BMD of lumbar spine, which is predominantly trabecular bone. The impact of GH deficiency on BMD will be examined in the second part of study with GH deficient and sufficient models.