The in Vivo Glucuronide Conjugation of Radioactive Etiocholanolone and Androsterone by the Dog Kidney *

Abstract

It is recognized that the liver readily conjugates reduced steroids (1) so rapidly that, under normal conditions, reduced steroids are not recovered in an unconjugated form in plasma but rather occur as sulfate (2-4), glucuronide (5), and probably phosphate (6) t Markle Scholar in Medical Science. 1 Compounds referred to are etiocholanolone (3a-hydroxy-etiocholane-1 7-one); androsterone (3a-hydroxyandrostane-17-one); tetrahydrocortisol (3a, 11t8, 17a, 21-tetrahydroxy-pregnane-20-one); tetrahydrocortisone (3a, 17a, 21-trihydroxy-pregnane-11, 20-dione); allo-tetrahydrocortisol (3a, 11,8, 17a, 21-tetrahydroxy-allopregnane-20-one); allo-tetrahydrocortisone (3a, 17a, 21-trihydroxyalldpregnane-11, 20-dione).2 Dubrulle and Claeys (9) measured unconjugated plasma 17-ketosteroids in 16 normal adolescents and found 7 to 28 Atg per 100 ml. 3 Recently, this clinical entity was named etiocholanolone fever in order to differentiate it from the familial Mediterranean fever on one hand, and the many periodic fevers on the other (11). ent in the urine during the same symptomatic episode. When the patients were afebrile and without symptoms, the 24-hour urinary 17-ketosteroid patterns were normal, and unconjugated etiocholanolone was not detected in the plasma. It was postulated that an attack of this type of fever might be associated vith 1) transient overproduction of etiocholanolone and/or 2) an intermittent inability to conjugate. The presence of conjugated etiocholanolone in urine and its absence in plasmiia during an attack of periodic fever is difficult to reconcile unless another organ in addition to the liver is involved in conjugation.The rapid clearance of etiocholanolone and androsterone, after intravenous injection (12) and oral and intravenous administration of testosterone (13-15), suggests the possibility that these compounds may be conjugated by another organ besides the liver. The reports of Dutton (16)

Sites of in vivo extraction and interconversion of testosterone and androstenedione in dogs

“…Furthermore, testosterone glucuronide is not solely made in the liver but also in the mesenteric area and in the kidney, a finding which is in agreement with in vitro (17) and in vivo studies (35). Inside the liver and the kidney, testosterone glucuronide does not seem to derive uniquely from tissue testosterone.…”

Metabolism of <i>p</i>-Aminohippurate and its Relevance in Man

“…A well-known metabolic function of the kidney is the conjugation of several exogenous and endogenous substances with glycin, glucuronate, sulphate, glutamine, and acetate [2][3][4]10,15,16], One of the substances known to be partially conjugated with acetate in a large variety of species including man is /y-aminohippurate (PAH), a widely used indicator of the renal plasma flow. In our recent study [8] we could show that in the rat complex and variable metabolic changes of PAH occur to an extent which may invalidate the results of PAH clearance determinations in this species.…”

On the Rate of Formation of Steroidal Glucuronosides in Patients with Familial and Acquired Jaundice*

“…To explain why the defect in steroid glucuronoside formation was quantitatively less striking than for bilirubin and menthol in MB, GC, and AL, extrahepatic glucuroconjugation of steroid may be postulated. In vitro (40,41) and in vivo (42,43) experiments have demonstrated the capacity of kidney and gastrointestinal tract to carry out glucuronic acid conjugation. Alternatively, one may theorize that the affinity of the conjugating system for reduced steroid is greater than for the other substrates tested.…”