Genetic deficiency of androsterone UDP-glucuronosyltransferase activity in wistar rats is due to the loss of enzyme protein

Hepatic microsomal UDP-glucuronosyltransferases towards androsterone and testosterone were purified by chromatofocusing and UDP-hexanolamine affinity chromatography in Wistar rats which had genetic deficiency of androsterone UDP-glucuronosyltransferase activity. In rats with the high-activity phenotype, androsterone (the 3-hydroxy androgen) UDP-glucuronosyltransferase was eluted at about pH 7.4 and had a subunit M(r) of 52000, whereas testosterone (the 17-hydroxy steroid) UDP-glucuronosyltransferase was eluted at about pH 8.4 and had a subunit M(r) of 50000. The transferase that conjugates both androsterone and testosterone was eluted at about pH 8.0, had subunit M(r) values of 50000 and 52000, and appeared to be an aggregate or hybrid of androsterone and testosterone UDP-glucuronosyltransferases. In rats with the low-activity phenotype, androsterone UDP-glucuronosyltransferase was absent, whereas testosterone UDP-glucuronosyltransferase was eluted at around pH 8.5, with a subunit M(r) of 50000.