In vitro metabolism of testosterone to 17ß-hydroxy-5α-androstane-3-one and 5α-androstane-3α, 17ß-diol by the rat intestine (original) (raw)
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Ileal metabolism in vitro of testosterone to 4-androstene-3 alpha, 17 beta-diol
Journal of steroid biochemistry, 1983
Testosterone metabolism to 4-androstene-3 alpha, 17 beta-diol by the 800 g supernatant fraction of ileum from male and female rats was investigated. Ileal production of this testosterone metabolite was higher in mature female animals than in mature males. This difference could be eliminated by administration of large doses estradiol-17 beta to mature male rats. Immature animals showed low ileal production of 4-androstene-3 alpha, 17 beta-diol before being weaned from their mother.
Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo
Gut, 1982
We have shown previously that the capacity of the jejunal mucosa to oxidise testosterone to the weaker androgen, androstenedione, by the enzyme 17j3-hydroxysteroid dehydrogenase (1 7f3-HSD), is considerable. The present study extends these earlier observations by measuring 1 7,B-HSD activity in different regions of the gastrointestinal tract, by investigating the potential for testosterone metabolism by slices and everted sacs of rat jejunum, and estimating the contribution of intestinal testosterone metabolites to circulating levels of plasma androgens, by portal vein sampling in the rat, in vivo. 17f3-HSD activity in homogenates of gastric and duodenal mucosa was significantly higher than that in jejunum, and was also present in ileum and colon. In addition to androstenedione, slices and everted sacs of rat jejunum produced various metabolites, one of which was probably dihydrotestosterone. It was not, however, a major metabolite in vivo. It is suggested that 5a-reduction may be favoured in vitro by a lower oxidation-reduction potential resulting from tissue anoxia. The major portal vein metabolite was androstenedione, the same major metabolite produced by mucosal homogenates. We conclude that oxidation of testosterone is the major metabolic pathway in intestinal mucosa and the capacity of the gastrointestinal tract to reduce the potency of testosterone is considerable. Our findings suggest that the gut, rather than the liver, is responsible for the failure of oral testosterone to provide effective androgen replacement therapy. The qualitative difference in testosterone metabolism between in vitro and in vivo preparations emphasises the need for caution in the interpretation of similar in vitro experiments. In a previous study we demonstrated that homogenates of rat and human jejunal mucosa can oxidise testosterone to the weaker androgen androstenedione.' This conversion was independent of gut bacteria. The enzyme responsible for this conversion, 1 7f3-hydroxysteroid dehydrogenase (1 7f-HSD), was present at high specific activity and the overall capacity of the small intestine to perform this conversion appeared considerable. This suggested that the gut, like other nonendocrine tissues such as skeletal muscle,2' lung,4 and adipose tissue,' 6 may play a significant role in the peripheral metabolism of testosterone. Previous reports7"1' have indicated that mammalian intestinal mucosa is also capable of reducing testosterone in relatively minor amounts to a variety of 5areduced metabolites, including the more potent metab
Journal of Steroid Biochemistry, 1983
It has recently been shown that 3p,li'/Gdihydroxy-5a-androstane (3/%diol), a known testosterone metabelite, may be further hydroxylated in position 6 and 7. Because of the possible involvement of 3&diol in the control of gonadotrophin secretion. this work was aimed at investigating the effects of 3/$,6a,l7#& trihydroxy-5oc-androstane (ba-triol), 3/$7a, I7B-trihydroxy-5a-androstane (7a-trio]), 3fi.6~. 17p-trihydroxy-Sa-androstane (6/I-triol) and 3B,7b,l7fi-trihydroxy-5a-androstane (7/?-triol) on the secretion of LH, FSH and prolactin in long term castrated male rats.
Acta Endocrinologica, 1980
Homogenates of normal or cryptorchid, human testes were incubated with [3H]testosterone and a NADPH-generating system. [3H]4-andostene,7\g=a\,17\ g=b\-di ol \ x=req-\ 3-one (7\g=a\-OH-testosterone)was isolated and identified from such incubations. To our knowledge this is the first demonstration that 7\g=a\-OH-testosteroneis a metabolite of testosterone in the human testis. 4-Andro-stene,6\g=b\,17\g=b\\x=req-\ diol-3-one (6\g=b\-OH-testosterone) and 4-androstene, 16\ g=a\ , 17\ g=b\ \ x=r eq-\ diol-3-one (16\g=a\-OH-testosterone) were also identified as testosterone metabolites. The specific activity of both testosterone 6\g=b\-and 16\g=a\-hydroxylase was higher than that of 7\g=a\-hydroxylase.Pre-pubertal or cryptorchid human testis tissues seem in our study to have higher testosterone 6\g=b\and 7\g=a\-hydroxylase activity than normal
Reproduction, 1973
Mean serum testosterone concentration in the 27-day-old prepubertal Holtzman rat was 0\m=.\25 ng/ml, much lower than that observed in the adult male, 5\m=.\5 ng/ml. Within 15 min after the intravenous injection of rat LH (in a dose of 400 ng-equiv. NIH-LH-S1/100 g body weight) serum testosterone concentration in the prepubertal rat increased approximately fivefold. Maximal elevation of serum testosterone to levels as high as those observed in the adult male occurred 1 hr after intravenous injection of rat LH. Serum testosterone returned to`control' levels within 2 hr of the intravenous injection of a small dose of rat LH. A dose-response relationship existed between serum testosterone and the dose of rat LH injected intravenously, over the range 25 to 1600 ng-equiv. NIH-LH-SI/100 g body weight.
Metabolism of Testosterone In Vitro by Hypothalamus and other Areas of Rat Brain
Andrologia, 2009
Inasmuch as several laboratories have reported the ability of brain to convert testosterone to Sa-androstanolone (Sholeton and Werk -1969; Rommerts and van der Molen -197 l), we have thought it of importance to determine the relative extent of conversion by different discrete areas of rat brain incubated with testosterone 14C in vitro. Three other groups have investigated this problem. and have reported results in the rat that confict with each other, while found that all areas of fetal human brain showed similar activity.
Acta Histochemica, 2015
The culminating phase of ageing in males-andropause is characterized by enhanced activity of the hypothalamic-pituitary-adrenal axis and frequent glucocorticoid excess. In parallel, free testosterone deficiency provides the baseline hormonal milieu for the ageing male. The aim of this study was to illustrate (using diverse microscopic and biochemical methodologies) the effects of testosterone application on the capacity for adrenocorticotropic hormone (ACTH) and corticosterone secretion in a rat model of the andropause. Middle-aged Wistar rats were divided into sham-operated (SO; n = 8), orchidectomized (Orx; n = 8) and testosterone treated orchidectomized (Orx + T; n = 8) groups. Testosterone propionate (5 mg/kg b.w./day) was administered for three weeks, while SO and Orx groups received the vehicle alone. ACTH cells and the adrenal cortex were stained using immuno-histochemical, immuno-fluorescent and histochemical procedures. Circulating concentrations of testosterone, estradiol, ACTH and corticosterone, as well as the adrenal tissue corticosterone levels were measured by immunoassays. Testosterone application led to increased (p < 0.05) serum concentrations of sex steroids. Consequently, in Orx + T rats the ACTH cell nuclei volume increased (p < 0.05) by 34%, while the volume density of ACTH cells and their relative intensity of fluorescence decreased (p < 0.05) by 46% and 21%, respectively, in comparison with the corresponding parameters in the Orx group. Testosterone also induced vasodilatation in the adrenocortical zona fasciculata, and decreased (p < 0.05) the ACTH concentrations and adrenal tissue corticosterone levels by 38% and 31%, respectively, compared to the Orx group. In conclusion, testosterone administration caused a decrease in the capacity for ACTH and corticosterone secretion in a rat model of the andropause.