REGULATION OF THE ACTIVITIES OF THE ENZYMES INVOLVED IN THE METABOLISM OF STEROID HORMONES IN RAT LIVER: THE EFFECT OF 19-NORTESTOSTERONE AND THE INFLUENCE OF CYPROTERONE ACETATE ON THE ACTION OF TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE

ABSTRACT The androgens testosterone and 5α-dihydrotestosterone, the anabolic drug 19-nortestosterone and the anti-androgen cyproterone acetate were investigated with regard to their modifying action on the sexual differentiation of the activities of rat liver enzymes involved in steroid hormone metabolism. The activities of the enzymes (Δ4-5α-hydrogenase, 20-ketoreductase, 3α-and 3β-hydroxysteroid dehydrogenase, NAD- and NADP-dependent Δ4-3β-hydroxysteroid dehydrogenase, total steroid hydroxylases, 7α- and 16α-hydroxylase) were determined in cell-free liver fractions of male animals castrated on day 25 of life and killed on day 90; and of castrated animals which, from day 75 to 89 received daily sc injections (0.3 mg/100 g body weight) of the anabolic drug or the androgen only or in combination with cyproterone acetate (3 mg/100 g body weight). With the exception of 7α-hydroxylase castration leads to a feminization of the enzyme activity pattern. However, the degree of feminization varies from enzyme to enzyme. The administration of testosterone or of 5α-dihydrotestosterone reverses the effect of castration. With 5α-dihydrotestosterone activity values were reached which in some cases were significantly higher than those obtained with testosterone. Although both androgens restored the enzyme activities to the normal male values, neither androgen was able to compensate for the weight loss of the seminal vesicles in the dose administered. The administration of 19-nortestosterone in the same dose as testosterone is only 30 % as effective in restoring the weight loss of the seminal vesicles, but leads to identical activities of Δ4-5α-hydrogenase and of hydroxysteroid dehydrogenases as are found for testosterone. 19-Nortestosterone is without influence on the activities of total steroid hydroxylases and of 16α-hydroxylase. 16α-Hydroxylase is the only enzyme in which the activity enhancing effects of testosterone or of 5α-dihydrotestosterone can be completely blocked by the simultaneous administration of the anti-androgen cyproterone acetate. In all other enzyme activities the anti-androgen does not interfere with the effect of the androgens although it blocks their action on the weight restitution of the seminal vesicles by 60–70 %. 7α-Hydroxylase does not exhibit any androgen dependency. Neither castration nor the subsequent administration of the two androgens, or of the anabolic drug leads to any alterations in activity. However, it is interesting to note that the administration of cyproterone acetate does cause an increase in activity.

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Sex-specific action of antiandrogens on androgen induced changes in hepatic microsomal 3β-hydroxysteroid dehydrogenase and 5α-reductase activity in the rat

Acta Endocrinologica ◽

10.1530/acta.0.0980261 ◽

1981 ◽

Vol 98 (2) ◽

pp. 261-266 ◽

Cited By ~ 8

Author(s):

E. Rodney Lax ◽

Herbert Schriefers

Keyword(s):

Enzyme Activities ◽

Cyproterone Acetate ◽

Reductase Activity ◽

Hydroxysteroid Dehydrogenase ◽

Female Rats ◽

Male Rats ◽

Induced Changes ◽

Intrinsic Effect ◽

Gonadal Status ◽

Antiandrogenic Activity

Abstract. The ability of two antiandrogens, cyproterone acetate and flutamide, to block the induction of microsomal 3β-hydroxysteroid dehydrogenase and repression of microsomal 5α-reductase in rat liver following administration of 5α-dihydrotestosterone was investigated in male and female castrated and female gonadintact rats. Although both antiandrogens blocked the effects of 5α-dihydrotestosterone on the seminal vesicles and uteri of gonadectomized rats at the doses employed, cyproterone acetate showed no antiandrogenic activity against the two enzyme activities. On the contrary when cyproterone acetate was administered alone it elicited a response similar to that seen after androgen administration; when given simultaneously with 5α-dihydrotestosterone, the induction of 3β-hydroxysteroid dehydrogenase activity was greater than after either steroid alone. In contrast the non-steroidal antiandrogen, flutamide, which had no intrinsic effect on either enzyme activity, effectively blocked 5α-dihydrotestosterone mediated changes in the enzyme activities of female rats regardless of gonadal status. However the influence of 5α-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.

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How to Maintain a Healthy Body Weight

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.4.208 ◽

2006 ◽

Vol 76 (4) ◽

pp. 208-215 ◽

Cited By ~ 10

Author(s):

Astrup

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Weight Loss ◽

Body Weight ◽

Glycemic Index ◽

Dairy Products ◽

Weight Control ◽

Healthy Body Weight ◽

Healthy Body

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

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Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.1.28 ◽

2006 ◽

Vol 76 (1) ◽

pp. 28-33 ◽

Cited By ~ 7

Author(s):

Yukari Egashira ◽

Shin Nagaki ◽

Hiroo Sanada

Keyword(s):

Body Weight ◽

Urinary Excretion ◽

Enzyme Activities ◽

Treated Group ◽

Control Group ◽

Puromycin Aminonucleoside ◽

Low Level ◽

Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

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Effects of Cyproterone Acetate on Body Weight and Food Intake

PsycEXTRA Dataset ◽

10.1037/e665992011-270 ◽

1973 ◽

Author(s):

William W. Beatty ◽

Thomas R. Vilberg ◽

Paul B. Revland

Keyword(s):

Body Weight ◽

Food Intake ◽

Cyproterone Acetate

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HEMMUNG VON TESTOSTERONABHÄNGIGEN DIFFERENZIERUNGSVORGÄNGEN DER MÄNNLICHEN RATTE NACH DER GEBURT

Acta Endocrinologica ◽

10.1530/acta.0.0540227 ◽

1967 ◽

Vol 54 (2) ◽

pp. 227-240 ◽

Cited By ~ 19

Author(s):

F. Neumann ◽

J. D. Hahn ◽

M. Kramer

Keyword(s):

Sexual Behaviour ◽

Cyproterone Acetate ◽

Post Partum ◽

Sexual Attitude ◽

Normal Male ◽

Corpora Lutea ◽

List Type ◽

Newborn Rats ◽

Neonatal Treatment ◽

Triangular Shape

ABSTRACT Male newborn rats were injected with 2 mg of an antiandrogen (1,2α-methylene-6-chloro-pregna-4,6-dien-17α-ol-3,20-dione-17α-acetate = cyproterone acetate) daily from their 1st to their 14th day of life. The following effects of this treatment were observed in these animals after onset of sexual maturity: 84% of the animals are unable to reproduce. Penis: the frenulum is broadened to a lamina of triangular shape, which almost completely prevents the preputium from being pushed back. These males show a rather insufficient male sexual behaviour towards females in oestrus. After castration and ovar implantation, some of the treated animals show true corpora lutea and at attempts of cohabitation partially female sexual behaviour towards normal male animals. From these results it can be concluded, that differentiation of the penis is not completed at the time of birth. The infertility of the animals may be caused by the penile changes (difficulties with intromission) as well as by the aimless sexual behaviour. This aimless sexual behaviour, the ability to produce true corpora lutea and finally their partially female sexual attitude under the influence of the hormones from the implanted ovaries led to the conclusion, that the above described neonatal treatment apparently inhibited testosterone-depending post partum developments of sexual differentiation in hypothalamic centers.

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