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|Title:||Metabolism of Testosterone, Progesterone and Androstenedione in the Liver, Testes, Hypothalamus and Cortex of Normal and Testicular Feminized (Tfm) Mice|
|Authors:||Daley, Daniel James|
|Department:||Medical Sciences (Growth and Development)|
|Keywords:||Medical Sciences;Medical Sciences|
|Abstract:||<p>The in vitro metabolism of testosterone, progesterone and androstenedione was studied in liver, testes, hypothalamus and cortex incubations of normal BALB/c♂, BALB/c♀ and a number of sex-mutant mice carrying the testicular feminization (Tfm) and sex-reversal (sxr) genes.</p> <p>The metabolism of testosterone was studied in liver homogenates of BALB/c♂ , Tfm (o⁺)⚥ and Tfm (oʰᵛ)⚥. Androstenedione was identified as the major metabolite of testosterone, in all incubations, indicating the presence of 17β-hydroxysteroid dehydrogenase activity. Comparison of the percentage conversions of testosterone to androstenedione suggested that of the three genotypes studied, the activity of 17β-hydroxysteroid dehydrogenase was lowest in the Tfm (oʰᵛ) liver.</p> <p>Similarly, the metabolism of testosterone and progesterone was studied by double-labelled tracer experiments using testes minces from BALB/c⚥ , Tfm (o⁺)⚥ and Tfm (oʰᵛ)⚥ mice. The conversion of progesterone to testosterone was greatest in BALB/c♂ incubations and least in the Tfm (o⁺) incubations. These data suggest that the relative activities of the 17-ketoreductase for the conversion of androstenedione to testosterone are in the order: BALB/c♂ > Tfm (oʰᵛ) ⚥ > Tfm (o⁺).</p> <p>Progesterone metabolism was studied in testis incubations of normal male (BALB/c♂), testicular-feminized, sex-reversed (Tfm+(oʰᵛ) Blo/+++, sxr/+ ♂) and sex-reversed (+Ta++/+++, sxr/+♂) mice. Comparison of the amounts of androstenedione and testosterone formed from P suggests that differences are present in the relative activity of the testis 3-ketoreductase. The relative activity is in the order BALB/c♂ > +Ta++/+++, sxr♂ > Tfm+(oʰᵛ) Blo/+++, sxr♂.</p> <p>The metabolism of androstenedione was also studied in testes incubation of Tfm (o⁺)⚥ and Tfm (oʰᵛ)⚥ mice. The formation of testosterone was similar in all incubations. A number of unidentified metabolites of androstenedione were detected in the Tfm (oʰᵛ)⚥ incubations which were not present in the Tfm (o⁺) incubations.</p> <p>Finally, the aromatization of testosterone was studied in hypothalamus and cortex incubations of normal BALB/c♂, BALB/c♀, and testicular feminized Tfm (o⁺)⚥ and Tfm (oʰᵛ)⚥mice. A new, rapid method was developed for studying aromatization based toluene-sodium hydroxide partitioning and a novel estrogen methylation procedure known as extractive alkylation. Using this method the formation of estrone and estradiol was detected. The conversion of testosterone to estradiol by hypothalamus minces was about 1.5 times greater in normal BALB/c♂ than BALB/c♀ and about the same as in Tfm (o⁺) and Tfm (oʰᵛ). Total aromatization by cortex minces was about 30-50% that of the hypothalamus. The major metabolite of testosterone in normal BALB/c ♂ and BALB/c ♀ incubations was estrone while in the Tfm (o⁺) and Tfm (oʰᵛ) incubations it was estradiol-17β.</p> <p>The studies confirm the work of others which suggests that the metabolism of steroids is altered in the liver and testis of the Tfm (o⁺)/Y⚥ mouse. The present work extends these observations to include a number of other mice carrying the Tfm and sxr genes. Using the extractive alkylation technique aromatization was detected in Tfm hypothalamus and although the overall quantitative yields of estrogen from testosterone were similar to normals, qualitative differences were evident which may be significant to the explanation of altered hypothalamic-pituitary gonadotrophin relationships in Tfm (o⁺) and Tfm (oʰᵛ) mice.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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