Untersuchungen �ber den Stoffwechsel von Testosteron und ?4-Androstendion in der Leber des Menschen

Engelhardt, D.; Eisenburg, J.; Unterburger, P.; Karl, H. J.

doi:10.1007/bf01485004

Cited by 11 publications

(3 citation statements)

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“…This effect could be explained by qualitative and quantitative alterations of the androgen-metabolizing enzyme activity in cirrhotic liver tissue [3,4] . cirrhosis) results in a drastic increase in plasma T levels after oral T administration.…”

Section: Discussionmentioning

confidence: 99%

“…cirrhosis) results in a drastic increase in plasma T levels after oral T administration. This effect could be explained by qualitative and quantitative alterations of the androgen-metabolizing enzyme activity in cirrhotic liver tissue [3,4] . The demonstration of intra-and extrahepatic shunts in compensated liver cirrhosis [12] provides a possible alternative interpretation of our findings.…”

Section: Discussionmentioning

confidence: 99%

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Influence of sex, testicular development and liver function on the bioavailability of oral testosterone

Nieschlga

Cüppers

Wickings

1977

Eur J Clin Investigation

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The bioavailability of orally administered testosterone was investigated in normal and hypogonadal men, prepubertal boys, normal women, and in patients with fatty liver, liver cirrhosis and surgical portocaval shunts. Peripheral testosterone concentrations remained unchanged in normal men and men with fatty liver, whereas a steep increase was observed in all other groups. The greatest increase was seen in patients with compensated liver cirrhosis and with portocaval shunts. The steep increase of peripheral testosterone in boys, women and hypogonadal men is attributed to their having a lower activity of androgen-metabolizing liver enzymes than normal men. The increase in patients with cirrhosis is most likely caused by intra- and extra-hepatic portocaval shunts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Influence of sex, testicular development and liver function on the bioavailability of oral testosterone

Nieschlga

Cüppers

Wickings

1977

Eur J Clin Investigation

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“…It seems reasonable to assume that the existence of pituitary hormones participating in the control of hepatic enzyme activities is not limited to rats. In man, sexual differences with respect to liver metabolism of steroids have recently been described (22), and other sexual differences with respect to hepatic lipid metabolism also occur in man (23). In this connection it is also of interest that Kappas and collaborators recently have indicated the possibility of pituitary regulation of hepatic heme biosynthesis (24,25).…”

Section: Livermentioning

confidence: 97%

On the obligatory role of the hypophysis in sexual differentiation hepatic metabolism in rats.

Gustafsson

Stenberg

1976

Proc. Natl. Acad. Sci. U.S.A.

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The hepatic metabolism of 444-14C]androstene-3,17-dione and 5a[4-'4Cjandrostane-3a,17f3-diol was studied in castrated and hypophysectomized male rats with a transplanted pituitary under the kidney capsule. The effects of testosterone propionate and estradiol benzoate on liver metabolism were also studied in these experimental animals. It was found that the autonomous pituitary secreted a "feminizing factor" that transformed the male type of steroid metabolism characteristic of hypophysectomized rats into a female type of metabolism. Hypophysectomized rats were unresponsive towards androgen action on the liver and did not respond with feminized hepatic metabolism after treatment with estradiol benzoate. It is concluded {hat estrogenic action on liver enzymes is mediated via modulation of the secretion of a central (probably hypothalamic) "feminizing factor inhibiting factor" and that sex hormonal effects on hepatic metabolism only occur in the presence of a pituitary in situ. The metabolism of steroid hormones in rat liver shows large sexual differences (1-5). This differentiation of hepatic metabolism, which begins at about 4 weeks of age and is almost completed at about 8-10 weeks of age, is manifested due to active processes in both sexes (6-9). The female metabolic type is maintained by a pituitary factor, without gonadal influence, whereas the male metabolic type seems to be maintained by testicular androgens acting directly upon the liver in the presence of an intact pituitary (2, 10-13).The male type of hepatic metabolism is irreversibly determined or "programmed" at birth by testicular androgen (5,14,15); if castrated during the neonatal period, male rats develop a female type of metabolism when adult. In animals exposed to androgen at birth (i.e., normal males and androgenized females), the male type of hepatic metabolism is temporarily feminized after treatment with estrogen (5, 6). Castration of adult male rats leads to partial feminization of certain enzyme activities in the liver whereas other enzymes retain their male characteristics (5,12 Incubations. The animals were killed by cervical dislocation and the liver was excised and chilled to 0-+4'. From a 20% (wt/vol) homogenate in a modified Bucher medium (16), microsomal and soluble enzyme fractions were prepared by differential centrifugation (6). The microsomes were resuspended in the buffer. Cytosol from about 0.6 g and microsomal suspension from about 0.1 g of liver tissue were incubated at 370 in the presence of an NADPH-regenerating system (5) with 500 ,ug of 4-[4-'4C]androstene-3,17-dione (specific activity 0.49 ,uCi/mg). 5a-[4-'4C]Androstane-3a,17f3-diol (specific activity 3.0 ,uCi/mg), 200 ,ug, was incubated with microsomal suspension from about 0.5 g of liver tissue. The conditions of the incubations were designed to give conversions linear with time and enzyme concentration. Small changes in substrate and cofactor amounts did not affect the total conversion of substrate.The steroids were extracted from the incubation medium w...

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Male Sex Hormones, Analogs, and Antagonists

Brueggemeier

2010

Burger's Medicinal Chemistry and Drug Discovery

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The steroid testosterone is the major circulating sex hormone of the male and serves as the prototype for the androgens, the anabolic agents, and androgen antagonists. The endogenous androgens are biosynthesized from cholesterol in various tissues in the body; the majority of the circulating androgens are made in the testes under the stimulation of the gonadotropin luteinizing hormone ( LH ). The reduction of testosterone to dihydrotestosterone is necessary for the androgenic actions of testosterone in many androgen target tissues such as the prostate; the oxidation of testosterone by the enzyme aromatase produces estrogens. The androgenic actions of testosterone and dihydrotestosterone are due to their binding to the androgen receptor, followed by nuclear localization, dimerization of the receptor complex, and binding to a specific DNA sequence. This binding of the homodimer to the androgen response element leads to gene expression, stimulation or repression of the synthesis of new mRNA, and subsequent protein biosynthesis. The synthetic androgens and anabolics were prepared to impart oral activity to the androgen molecule, to separate the androgenic effects of testosterone from its anabolic effects, and to improve upon its biological activities. Novel nonsteroidal androgens, termed selective androgen receptor modulators, were developed to impart agonist activity in selective tissues. Drug preparations are used for the treatment of various androgen‐deficient diseases, for the therapy of diseases characterized by muscle wasting and protein catabolism, for postoperative adjuvant therapy, and for the treatment of certain hormone‐dependent cancers. The two major categories of androgen antagonists are the antiandrogens, which block interactions of androgens with the androgen receptor, and the inhibitors of androgen biosynthesis and metabolism. Such compounds have therapeutic potential in the treatment of acne, virilization in women, hyperplasia and neoplasia of the prostate, and baldness and male contraception.

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Untersuchungen �ber den Stoffwechsel von Testosteron und ?4-Androstendion in der Leber des Menschen

Cited by 11 publications

References 3 publications

Influence of sex, testicular development and liver function on the bioavailability of oral testosterone

Influence of sex, testicular development and liver function on the bioavailability of oral testosterone

On the obligatory role of the hypophysis in sexual differentiation hepatic metabolism in rats.

Male Sex Hormones, Analogs, and Antagonists

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