The Mode of Action of Anabolic Agents

Castration of adult male rats produces a delayed (by approximately 1 mo), permanent hypophagia and reduction in weight gain. This contrasts with the rapid, transient hyperphagia and increased weight gain caused by ovariectomy in female rats. Injections of testosterone propionate (TP) stimulate food intake and weight gain in castrated males. Neither 5alpha-reduction nor aromatization of the testosterone molecule plays an important role in the stimulation of these measures by TP. The 5alpha-reduced metabolite of TP, 5alpha-dihydrotestosterone propionate (DHTP), is less effective in increasing eating and weight gain than is TP. Very high doses of TP may actually reduce weight gain with prolonged treatment (2-6 wk). It is likely that this reduced weight gain is due to aromatization of TP to an estrogen. The nonaromatizable androgen, DHTP, does not reduce weight gain even in very high doses, and concurrent progesterone injections reverse the weight-reducing actions of high TP doses.