Inability of oxymetholone to elicit an erythropoietin-hypersecretory state in orchidectomised male mice

The erythropoietin-hypersecretory state (EPO-HS) is a condition elicited by several inducers that is easily observed in hypertransfused-polycythaemic rats and mice, in which hypoxia-stimulated erythropoietin (EPO) secretion is higher than in polycythaemic controls. Steroids with different androgenic/anabolic ratios have proved to be potent inducers of EPO-HS. However, both steroid activities do not appear to have similar importance. The purpose of the present study was to assess the ability of oxymetholone, a synthetic derivate of testosterone that shows the highest anabolic/androgenic ratio, to elicit an EPO-HS. Mice were orchidectomised at 30 days of age. One month later, groups of animals were injected with graded doses of oxymetholone for 4 weeks. All orchidectomised mice were hypertransfused 4 days after the end of the injection period. On the next day, they were exposed to air maintained at 506.5 mbar for 6 h to stimulate EPO production. Plasma EPO titre was determined by immuno-analysis and taken as a reflection of the EPO production rate. Kidney, seminal vesicle and levator ani muscle weights were registered as index of renotrophic, androgenic and anabolic effects, respectively. The steroid brought out a significant anabolic, and a poor androgenic, response. Any of the doses of oxymetholone tested increased EPO production in orchidectomised polycythaemic mice and, therefore, an EPO-HS was not induced. This finding, coupled with previously reported data, suggests that only steroids showing a certain degree of androgenic action have the capacity to evoke an EPO-HS.