PhD

Abstract

thesisKidney slices from male CBA mice are able to conjugate ring A reduced 3-hydroxy steroids as glucuronides. Glucuronides are formed from pregnance-3?-o1-11,20-dione and pregnane-3?,17?-diol-11,20-dione. The Kidney did not from glucuronides from cortisol or corticosterone since it was able to reduce ring A. Most of the water soluble conjugates formed by the kidney are glucuronides. The liver can reduce ring A and can form glucuronide conjugates from cortisol and corticosterone. The liver can from glucuronides from pregnance-3?-o1-11,20-dione and pregnane-3?,17?-diol-11,20-dione. Glucuronides comprise about one-half of the total water soluble conjugates. The presence of the 17?-hydroxy group hinders the conjugation of C-21 steroids containing this chemical grouping in liver and kidney. This was show to be an interference with glucuronosly transferase causing a decreased glucuronide formation with 17- hydroxycorticosteroids. This effect was exhibited in the liver and kidney. In vitro conjugation of compound x was a glucuronide by the kidney was significantly decreased on the 1st, 5th, 13th and 21st days following 500 r of whole-body irradiation. Irradiation significantly decreased in the in vitro conjugation of compound x by the liver on the 5th and 21st days post-irradiation. The decrease in conjugation on the 1st day post-irradiation was non-significant and the decrease on the 13th day post-irradiation has a P value of (0.05<P<.1). This decrease in conjugation was reflected in the amount of steroid released by ?-glucuronidase hydrolysis. The in vitro conjugation of corticosterone by the liver was significantly decreased on the 21st day after irradiation with 500 r. The amount of glucuronide formed from corticosterone on the 21st day also decreased. There was no significant decrease in conjugation or glucuronide formation with corticosterone on the 1st, 5th, or 13th day post-irradiation. X-irradiation did not affect the rate of conjugation of compound x in the kidney. The control animals conjugated more compound x at the end of three hours than irradiated animals. The rates of conjugation of compound XIII and corticosterone in the liver were not altered by irradiation. The total amount of compound x and corticosterone conjugated by the irradiated animals' livers was slightly less than the total amount conjugated by the control animals' livers

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