Age- and sex-dependent stimulation of growth rate in rats by the adrenal inhibitor trilostane.
The effects of the adrenal inhibitor trilostane were examined in male and female rats to determine whether growth rate could be improved by lowering circulating plasma corticosterone concentrations. Dose-response studies revealed that in young female rats (125 g) trilostane lowered peak plasma corticosterone levels in a dose-dependent manner. In male rats plasma corticosterone concentrations were reduced only by very high doses of trilostane (200 mg/kg), while lower doses (2-8 mg/kg) actually increased them. Five growth studies were conducted using a total of 90 rats. In female animals, daily injections of trilostane (10 mg/day) caused an age-dependent increase in growth rate ranging from 11% in 127 g rats to 30% in 164 g rats. In three out of four experiments using females, food intake was slightly increased by the drug. Food conversion efficiency was improved consistently by trilostane by up to 18%. Trilostane-treated females had significantly heavier adrenal glands and livers, but lighter kidneys than control rats. When a complete carcass analysis was performed on one experimental group, no significant differences were found. Carcass component weights relative to control values were: body weight (103%), body water (105%), fat-free solids (103%), carcass weight (103%), body length (103%), body fat (95%) and gut content (96%). In male rats (160 g), daily injections of trilostane (10 mg) resulted in a steady and sustained depression of growth rate reflecting a similar fall in food intake, with no change in food conversion efficiency. It is concluded that in older female rats growth rate is constrained by physiological concentrations of glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000311:Adrenal Glands / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D006128:Growth / Q000187:drug effects*; D008297:Male; D009929:Organ Size; D051381:Rats; D012737:Sex Factors
D013196:Dihydrotestosterone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane