Effects of several androgens and steroid metabolites on erythropoietin production in the isolated perfused dog kidney

Abstract

In an attempt to clarify the role of the kidney in the action of several androgens and steroid metabolites on erythropoietin (ESF) production, ESF titers were measured in perfusates of isolated kidneys from dogs previously exposed to 4 hr hypoxia and perfused with blood containing testosterone (Test), 5α 17β hydroxy androstan 3 one (5αDHT), 5β 17β hydroxyandrostan 3 one (5βDHT), 19 nortestosterone (19 nor), oxymetholone (Oxy), fluoxymesterone (Fluoxy), 3α hydroxy 5β pregnane, 11,20 dione (3αOH5βpreg), or 3β hydroxy 5β pregnane 20 one (3βOH5preg). ESF levels in the perfusates were assayed in exhypoxic polycythemic mice. Test, 5αDHT, oxy, fluoxy, and 3βOH5βpreg were found to produce a significant increase in ESF levels in the kidney perfusates. 5βDHT, 19 nor, and 3αOH5βpreg failed to produce a significant elevation in erythropoietin titers in the perfusates of the isolated perfused kidneys. These data suggest that the 4-5 double bond and the spatial configuration of the hydrogen at the 5 position as well as the lack of a methyl group in the 19 position of the basic androstan nucleus are important in the ability of these steroids to stimulate kidney production of ESF.