Predominant Androgenic Component in the Induction of Erythropoietin-Hypersecretory State by 19-Nortestosterone in the Orchidectomised Mouse

Abstract

Erythropoietin-hypersecretory state (EPO-HS) has been defined as a condition, easily observed in hypertransfused-polycythaemic rats and mice as a consequence of several treatments, in which hypoxia-stimulated secretion of EPO is higher than in non-treated polycythaemic controls at equal levels of polycythaemia. Testosterone is a potent inducer of EPO-HS. Some steroids, such as 19-nortestosterone (19-NT) have a stronger anabolic activity, relative to androgenic activity, than others. All of them, however, induce almost the same degree of erythropoiesis in the polycythaemic mouse model. The present study was carried out to test the capacity of 19-NT to induce an EPO-HS and to establish which of the androgenic or anabolic activities is the predominant component in the erythropoietic action of the steroid. Seventy CF-1 mice were orchidectomised when aged 30 days. One month later, groups of 10 animals were injected s.c. 3 times a week for 4 weeks with 19-NT at doses of 0, 50, 100, 200, 400, 800, 1600 and 3200 μg/days. A group of entire male mice was used as normal controls. All mice were hypertransfused 4 days after the end of the injection period. On the next day, they were exposed to 506.5 mbar for 6 h. Plasma EPO titre (ELISA Medac Diagnostika, FRG) was determined 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. EPO production in response to hypoxia increased with increased doses of 19-NT. The derived linear regression between plasma EPO (mU/ml) and 19-NT log dose showed the following characteristics: slope, 42.50 ± 6.82; y-int., −50.68 ± 18.2; x-int., 1.192; r2, 0.8861; p 0.0016. Positive correlations were found between EPO production and kidney weight (r 0.8995, r2 0.8092, p 0.0023), seminal vesicle weight (r 0.9213, r2 0.8489, p 0.0011) and levator ani muscle weight (r 0.6851, r2 0.4694, p 0.0608). 19-NT thus induced an EPO-HS in orchidectomised mice when administered in pharmacological doses. This capacity was associated with renotrophic and androgenic effects of the steroid and apparently not related to its anabolic activity.