Comparative aspects of the metabolism and excretion of cortisol in three individual nonhuman primates

A radiometabolism study is described to provide the first comparative data on the time course, route, and characteristics of excreted [H-3]cortisol me tabolites in three nonhuman primates: the common marmoset (Callithrix jacch us), the long-tailed macaque (Macaca fascicularis), and the chimpanzee (Pan troglodytes). A low dose (40-100 mu Ci) of H-3-labeled cortisol was admini stered intravenously to one adult male of each species and the excreta coll ected over a 5-day period postinjection. The major proportion of radioactiv ity was excreted in the urine (>80%). Peak radioactivity in urine was recov ered within 5.5 h following injection in all three species, while in the fe ces peak levels of radioactivity were recovered within 26 h postinjection. In all three species, urinary metabolites were primarily excreted as conjug ates (61-87%), whereas the percentage of conjugated metabolites in feces wa s 50% or less. The number and relative abundance of urinary and fecal [H-3] cortisol metabolites were determined by reverse-phase highperformance liqui d chromatography (HPLC) and immunoreactivity of the radioactivity peaks was assessed by screening HPLC fractions with established cortisol, corticoste rone, and 11-oxoetiocholanolone enzyme immunoassays (EIA), the latter being a group-specific assay for measuring 11,17-dioxoandrostanes. HPLC separati on of urinary and fecal extracts revealed multiple peaks of radioactivity, several of which were common to all three species, The relative proportion of these peaks, however, differed considerably among species and between ur ine and feces, HPLC indicated that native cortisol was a major urinary excr etory product in the marmoset, while comparatively small amounts were prese nt in the urine of the macaque and chimpanzee. In contrast, in feces, corti sol was only detected in low amounts in the marmoset and was virtually abse nt in the macaque and chimpanzee. In all three species, one of the major ra dioactivity peaks showed a retention time comparable to 11-oxoetiocholanolo ne and high immunoreactivity in the 11-oxoetiocholanolone EIA. The measurem ent of urinary- and/or fecal-immunoreactive 11,17-dioxoandrostanes is there fore implicated for noninvasive assess; ment of adrenal function in Old Wor ld monkeys, New World monkeys, and great apes. (C) 2000 Academic Press.