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The enterohepatic recycling of estrogens in cystic fibrosis
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INTERCONVERSION OF DIRYDROTESTOSTERONE AND 3cr-ANDROSTANEDIOL IN TEE WC. aapdelaine, A., McKercher, c., boulenger, P., Chevalier, S., Bleau, C. and Roberts, K.D. Depcs of Med. and Biochem. univ. of Montreal and Meisonneuve-Rosemont Hosp. Montreal, Quebec, CANADA. It is well accepted that the in vivo edministration of k-endrortene-3a,l7Ddiol 3a,17D-diol) is more effective than dihydrotertorterone (DHT) to increere the weight of the canine prostate. Even though the tirrulrr accumulation of DHTin benign prortrtic hypertrophy (BPH) is controversial, the prortatic DHTcontenc is higher then thet of 3a,17D-diol in normal and hyperplastic canihe prostates. Conrequently, the interconversion of DET and 3a,i’lBdiol was investigated following the in vivo infusion as well as the in vitro perfurion of the two lobelled steroids under equilibrium conditionr. In vivo, at equilibrium, the peripheral interconversion of the two androgens greetly favored (3-fold) the formetion of DHT. Moreover, the acute or chronic administration of 3C&l’lg-diol to normel or castreted dogs resulted in a higher plasma level of DET, rather than 3a,i7P-diol, es eerly as sixty minutes following the injection. Superfurion experiments with slices of the cenine prortete gave the following results: the concentretion of DHT found within the tirrue wea 3 to 6-fold higher then the concentration of 3a,17Bdiol. DHTwes retained by the prostatic tisrue while 3a,l’/B-diol was not. Ihe interconversion of 30,17D-diol and DHT fevored the oxidetive pethwry. Furthermore, an increere in the concentration of 3a,17bdiol perfured resulted in l higher intratirsue concentration of DXT compered to the levels obteined when increered concentrations of DRT itself were perfused. These in vivo end in vitro experiments both show that 3a17Ddiol is a better precursor of intraprostatic DET then DHT itself and could certainly explain why 3a,l’lbdiol is a more efficient inducer of experimental BPH in the dog. METABOLISM OF STEROL HYDROPEROXIDES:
Smith, L.L.: Made Gowda, N.M.: Teng, J.I. Department of Human Biological Chemistry & Genetics., University of Texas Medical Branch; Galveston, Texas 77550; U.S.A. 36-Hydroxy-5a-cholest-6-ene-5-hydroperoxide and cholesterol' 7a-hydroperoxide are weakly mutagenic towards Salmonella typhimurium TA1537, the mutagenicity apparently arising from stimuBoth hydraperoxides are metabolized during lated increase in superoxiae and peroxide flux. In order to reconcile multiphasic dose-responses a study of the metabolism was bioassay. conducted. metabolites were recovered and Under conditions where both hydroperoxides were mutagenic, identified by high performance liquid chromatography on 3um particulate Zorbax SIL Columns irrigated with hexane-isopropyl alcohol (5O:l) (resolving all sterols implicated) and by infrared The Sa-hydroperoxide was rapidly isomerized to the 7a-hydroperoxide absorption spectrometry. and both were more slowly and less extensively reduced to th@ corresponding alcohols Sa-cholest6-ene-36,5-diol and cholest-5-ene-36,7a-diol respectively. Additionally, some 3&hydroxycholestThe 7a-hydroperoxide was not reverted to the Sa-hydroperoxide nor epimerized 5-en-7-one formed. Neither 36,5a-diol nor 36,7a-diol were isomerired or otherwise to cholesterol 76-hydroperoxide. All transformations occurred in good excess over heat-inactivated bacterial control Ialtered. Cell-free preparations of S. typhimurium TA1537 also were active in hydroperoxide ;incubations. These Observations offer-a basis for understanding the peculiar NitageniCitY isomerization. The isomerization appears to be the first such transformation recorded for dose-responses. (Supported by NIH grant ES-0239Q). bacteria.
-19
LoAdon BW3
WlP 7PN 6HP ENOL&O.
and
+ The
A Qrbup of normal females were compared with a similar group of female C.F. patients. ‘““38 l re was no si nificant difference in the total l xcre t i on or the proportion of ? he 3-Qlucuronide excreted but patients did s;l”ow a lower proportion excreted between 24 and 48 hours,, that they had a reduced lnterohepat ic recycl inQ of the adminI f:PPt::i
7s
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17
INTERCONVERSION OF DIRYDROTESTOSTERONE AND 3cr-ANDROSTANEDIOL IN TEE WC. aapdelaine, A., McKercher, c., boulenger, P., Chevalier, S., Bleau, C. and Roberts, K.D. Depcs of Med. and Biochem. univ. of Montreal and Meisonneuve-Rosemont Hosp. Montreal, Quebec, CANADA. It is well accepted that the in vivo edministration of k-endrortene-3a,l7Ddiol 3a,17D-diol) is more effective than dihydrotertorterone (DHT) to increere the weight of the canine prostate. Even though the tirrulrr accumulation of DHTin benign prortrtic hypertrophy (BPH) is controversial, the prortatic DHTcontenc is higher then thet of 3a,17D-diol in normal and hyperplastic canihe prostates. Conrequently, the interconversion of DET and 3a,i’lBdiol was investigated following the in vivo infusion as well as the in vitro perfurion of the two lobelled steroids under equilibrium conditionr. In vivo, at equilibrium, the peripheral interconversion of the two androgens greetly favored (3-fold) the formetion of DHT. Moreover, the acute or chronic administration of 3C&l’lg-diol to normel or castreted dogs resulted in a higher plasma level of DET, rather than 3a,i7P-diol, es eerly as sixty minutes following the injection. Superfurion experiments with slices of the cenine prortete gave the following results: the concentretion of DHT found within the tirrue wea 3 to 6-fold higher then the concentration of 3a,17Bdiol. DHTwes retained by the prostatic tisrue while 3a,l’/B-diol was not. Ihe interconversion of 30,17D-diol and DHT fevored the oxidetive pethwry. Furthermore, an increere in the concentration of 3a,17bdiol perfured resulted in l higher intratirsue concentration of DXT compered to the levels obteined when increered concentrations of DRT itself were perfused. These in vivo end in vitro experiments both show that 3a17Ddiol is a better precursor of intraprostatic DET then DHT itself and could certainly explain why 3a,l’lbdiol is a more efficient inducer of experimental BPH in the dog. METABOLISM OF STEROL HYDROPEROXIDES:
Smith, L.L.: Made Gowda, N.M.: Teng, J.I. Department of Human Biological Chemistry & Genetics., University of Texas Medical Branch; Galveston, Texas 77550; U.S.A. 36-Hydroxy-5a-cholest-6-ene-5-hydroperoxide and cholesterol' 7a-hydroperoxide are weakly mutagenic towards Salmonella typhimurium TA1537, the mutagenicity apparently arising from stimuBoth hydraperoxides are metabolized during lated increase in superoxiae and peroxide flux. In order to reconcile multiphasic dose-responses a study of the metabolism was bioassay. conducted. metabolites were recovered and Under conditions where both hydroperoxides were mutagenic, identified by high performance liquid chromatography on 3um particulate Zorbax SIL Columns irrigated with hexane-isopropyl alcohol (5O:l) (resolving all sterols implicated) and by infrared The Sa-hydroperoxide was rapidly isomerized to the 7a-hydroperoxide absorption spectrometry. and both were more slowly and less extensively reduced to th@ corresponding alcohols Sa-cholest6-ene-36,5-diol and cholest-5-ene-36,7a-diol respectively. Additionally, some 3&hydroxycholestThe 7a-hydroperoxide was not reverted to the Sa-hydroperoxide nor epimerized 5-en-7-one formed. Neither 36,5a-diol nor 36,7a-diol were isomerired or otherwise to cholesterol 76-hydroperoxide. All transformations occurred in good excess over heat-inactivated bacterial control Ialtered. Cell-free preparations of S. typhimurium TA1537 also were active in hydroperoxide ;incubations. These Observations offer-a basis for understanding the peculiar NitageniCitY isomerization. The isomerization appears to be the first such transformation recorded for dose-responses. (Supported by NIH grant ES-0239Q). bacteria.
-19
LoAdon BW3
WlP 7PN 6HP ENOL&O.
and
+ The
A Qrbup of normal females were compared with a similar group of female C.F. patients. ‘““38 l re was no si nificant difference in the total l xcre t i on or the proportion of ? he 3-Qlucuronide excreted but patients did s;l”ow a lower proportion excreted between 24 and 48 hours,, that they had a reduced lnterohepat ic recycl inQ of the adminI f:PPt::i
7s
whit stere