Testosterone-induced erythropoietin-hyper-secretory state in the absence of renal hypertrophy in hypophysectomized rats

Erythropoietin-hypersecretory state (EPO-HS) is a condition observed in hypertransfused-polycythemic rodents as a consequence of several experimental treatments in which stimulated secretion of EPO is higher than in non-treated polycythemic ones at equal levels of polycythemia. We have recently shown that chronic administration of testosterone propionate (TP) induces the appearance of an EPO-HS in adult female mice, which has been associated with the renal hypertrophy induced by the steroid. The present study was designed to test the hypothesis that long-term administration of TP also induces an EPO-HS in the hypophysectomized (H) rat, model in which the androgen does not induce kidney hypertrophy. Female Sprague-Dawley rats were hypophysectomized at day 30 of post-natal life. Three months later, they showed a 30% decrease in the circulating red cell mass (dilution method) and a 12% reduction in O2 consumption when compared to control entire rats (N). H rats were injected s.c. with 5mg TP 3 times/wk for 6 weeks. All rats (treated or non-treated N and H) were then transfused with homologous packed red cells (4 ml/100g) to depress EPO production. Plasma immunoreactive EPO titers (EPO-ELISA, Medac Diagnostika, Germany) after exposure to 506 mb for 6 h were similar in N and H polycythemic rats. However, piEPO concentration was significantly higher in TP-treated than in non-treated rats. TP did not increase kidney weight in H rats, whereas the renotrophic effect of the steroid was marked in N rats. These data confirm the hypothesis and suggest that the EPO-HS induced by testosterone is not related to the steroid-induced renal hypertrophy.