metribolone and Body-Weight

1. The effects of the active principles of S. rebaudiana (SR) on endocrine parameters of male rats were studied upon chronic administrations (60 days) of a concentrated, crude extract of its leaves, starting at prepubertal age (25-30 days old). 2. The following determinations were made: glycemia; serum levels of T3 and T4; available binding sites in thyroid hormone-binding proteins (T3R index); binding of [3H]R 1881 to prostate cytosol; zinc content in prostate, testis, submandibular salivary gland (SMG) and pancreas; water content in testis and prostate. The body weight gain and the final weight of testis, prostate, seminal vesicle, SMG and adrenal were also studied. 3. Results showed that the SR-treated group did not significantly differ from the control group, with exception to the seminal vesicle weight, which fell by about 60%. 4. It is concluded that if the SR extract does have some potential to decrease rat fertility at all, this effect is almost certainly not exerted on the male.

Topics: Animals; Body Weight; Endocrine Glands; Estrenes; Male; Metribolone; Organ Size; Plant Extracts; Prostate; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine; Zinc

Flutamide was used to investigate the mechanism involved in androgen responsive hepatic microsomal drug and steroid metabolism. We compared the antiandrogenic action of flutamide on the prostate to its effect on testosterone responsive hepatic microsomal benzo[a]pyrene hydroxylase (BPH) and testosterone reductase (TR) activities. Male Wistar rats, castrated as adults, were treated with 5 mumoles.kg-1.day-1 of testosterone enanthate subcutaneously for 10 days. Co-administration of increasing doses of flutamide caused a dose-dependent reduction in prostate to body weight ratios and, in the same animals, caused significant alterations in adult male hepatic microsomal BPH and TR activities. These doses of flutamide did not affect the serum testosterone levels. To test the possibility that the action of flutamide on androgen responsive hepatic microsomal drug and steroid metabolism may be similar to that occurring in the prostate, a tissue which contains an androgen receptor, we also studied the effect of flutamide on the binding kinetics of the high affinity hepatic cytosolic [3H]R1881 binding protein in vivo. Scatchard analysis of [3H]R1881 binding data revealed a reduction in the binding capacity of the hepatic cytosolic androgen binding protein in castrated animals treated with a combination of flutamide and testosterone enanthate at doses capable of maximally altering hepatic microsomal drug and steroid metabolism. No alteration in binding affinity occurred in this treatment group. However, a decreased binding affinity was found when flutamide alone was given. The binding kinetics of the hepatic cytosolic androgen binding protein were not altered in the castrated adult male with or without testosterone treatment. When flutamide was injected daily into the intact adult female rat, no effect was observed on either hepatic microsomal BPH or TR activities. Taken together, these data indicate that flutamide reduces hepatic cytosolic R1881 binding in the adult male rat, and this may explain some of the effects of this antiandrogen on testosterone-sensitive hepatic microsomal drug and steroid metabolism.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgen-Binding Protein; Anilides; Animals; Aryl Hydrocarbon Hydroxylases; Benzopyrene Hydroxylase; Body Weight; Castration; Cytosol; Estrenes; Female; Flutamide; Kinetics; Liver; Male; Metribolone; Organ Size; Rats; Receptors, Androgen; Sex Factors; Testosterone

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

Topics: Animals; Azoxymethane; Binding Sites; Body Weight; Colon; Colonic Neoplasms; Cyproterone; Cyproterone Acetate; Cytosol; Estrenes; Kinetics; Male; Metribolone; Orchiectomy; Rats; Rats, Inbred Strains; Receptors, Androgen; Rectal Neoplasms; Testosterone

Female rats were divided into a sedentary control and an exercise group that was trained by treadmill running 100 min/day for 13-15 wk. During the last 12 days of training, they were further subdivided into trained and sedentary groups that received either daily subcutaneous injections of cortisone acetate (CA) (100 mg/kg body wt) or the vehicle, 1% (wt/vol) carboxymethylcellulose. As a result of the exercise program, ventricular weights were 15% (P less than 0.01) heavier in the vehicle-treated runners than in the vehicle-treated controls, but there were no changes in cardiac androgen (methyltrienolone, R1881) or glucocorticoid (dexamethasone, DEX) cytosol-specific binding concentrations. Body weights were decreased by 11-12% in both CA-treated groups. Ventricular weights of the CA-treated controls were 11% (P less than 0.01) heavier than the weights of the vehicle-treated controls. The combination of exercise and glucocorticoid treatments resulted in ventricular weights that were 21% heavier than those in the vehicle-treated controls and 8 and 5% (P less than 0.05) greater than those resulting from CA and endurance training individually. Both R1881 and DEX binding were decreased in hearts of CA-treated animals from those of vehicle-treated animals, and exercise did not modify this response. These results show that glucocorticoid treatment can induce cardiac enlargement, and the combination of glucocorticoids and exercise can have additive effects on the growth, yet their mechanisms appear different.

Topics: Animals; Body Weight; Cardiomegaly; Dexamethasone; Estrenes; Female; Glucocorticoids; Heart Ventricles; Metribolone; Organ Size; Physical Exertion; Rats; Tritium

This study was undertaken to determine whether the exercise-induced sparing of glucocorticoid-induced muscle atrophy is related to increased androgen cytosol binding. Female rats were divided into a sedentary or an exercise group that was trained by treadmill running 100 min/day for 13-15 wk. During the last 12 days of training, each of these groups was further subdivided into groups that received daily subcutaneous injections of cortisone acetate (CA) (100 mg/kg body wt) or the vehicle 1% carboxymethyl cellulose. Exercise prevented 30-40% of the weight loss due to CA treatment in gastrocnemius and plantaris muscles. Scatchard analyses of specific binding of [3H]methyltrienolone (R1881), a synthetic androgen that binds to androgen receptors, were nonlinear in muscles from vehicle-treated sedentary and trained rats and were resolved by a two-component binding model. The lower affinity component, which was attributed to a glucocorticoid receptor, disappeared in muscles of glucocorticoid-treated animals as evidenced by linear Scatchard plots. Receptor concentrations of the androgenic component of [3H]methyltrienolone binding were similar in gastrocnemius and plantaris muscles in all treatment groups. In binding specificity studies of gastrocnemius muscles, the relatively high competition by various glucocorticoids and progesterone for [3H]methyltrienolone binding in the vehicle-treated groups was reduced by CA treatment. The lack of change in androgen cytosol receptor levels suggests that this is not a mechanism by which exercise protects against glucocorticoid-induced muscle atrophy.

Topics: Androgens; Animals; Body Weight; Cortisone; Cytosol; Estrenes; Female; Metribolone; Muscular Atrophy; Physical Exertion; Rats; Rats, Inbred Strains; Receptors, Androgen; Receptors, Glucocorticoid; Receptors, Steroid; Testosterone Congeners

Androgen binding has been studied in the quadriceps femoris of recently castrated adult and intact immature male and female rats using a variety of techniques for separating and measuring hormone-receptor complexes. [3H]Testosterone, [3H]androstanolone (or 5 alpha-dihydrotestosterone). [3H]methyltrienolone (a potent synthetic androgen), and [3H]estradiol bind to the androgen receptor. Affinities are identical for the first two hormones (Kd = approximately 70 pM) and lower for estradiol (Kd = approximately 0.2 nM), as determined by Scatchard plots of binding data. Competition experiments indicate that in addition to the nonradioactive steroids corresponding to the above-cited tritiated compounds, progesterone, cyproterone acetate (an antiandrogen), and spironolactone compete for [3H]androgen binding by the receptor, but diethylstilbestrol, moxestrol (a potent synthetic steroidal estrogen), and cortisol do not. 3 alpha- and 3 beta-androstanediols slightly inhibit testosterone binding. Therefore, striated muscle androgen receptor specificity is identical to that of all androgen receptors of target tissues which have been previously studied. Binding is abolished by pronase and heat treatment, and displays an approximate 7S sedimentation coefficient in low salt ultracentrifugation gradient analysis. Preliminary observations suggest hormone-induced receptor translocation into the nucleus. No evidence has been found for an independent estrogen receptor. In the course of the binding experiments, extensive metabolism of androstanoloe and testosterone was observed in muscle cytosol at 0-4 C, during the 2-h incubation period used for most binding studies. Metabolite formation can jeopardize the binding data, specifically altering the significance of competition experiments with relatively high concentrations of steroids approaching the Km of metabolizing enzymes. Therefore, most quantitative studies were performed in enzyme-free, receptor-containing cytosol preparations. In adult male rats castrated for 2 days, the concentration of receptor in the cytosol was of the order of 1 fmol/mg protein and corresponded to 72 fmol/mg tissue DNA (that is, 100 and 20 times less than that in corresponding prostatic cytosol, respectively). In the adult female rat 2 days after castration, the concentration of receptor in the cytosol was 0.34 fmol/mg protein. Treatment with testosterone pellets (20 mg for 15 days) increased androgen receptor concentration significantly. In spite of

Topics: 3-Hydroxysteroid Dehydrogenases; Androgens; Animals; Body Weight; Cytosol; Dihydrotestosterone; Estradiol; Estrenes; Estrogens; Female; Male; Metribolone; Muscles; Organ Size; Prostate; Rats; Receptors, Androgen; Receptors, Steroid; Sex Factors; Testosterone

Male rats rendered diabetic by IV streptozotocin (65 mg/kg body weight) were treated with exogenous insulin or testosterone. Charcoal-coated dextran and polyacrylemide gel electrophoresis techniques were employed in studying the characteristics of androgen (R1881) binding to prostate cytosol protein. In comparison with normal (N) rats, the replacement therapy of diabetic (D) animals with insulin (D + I) or testosterone (D + T) was able to restore epididymal weight (N = 0.40 +/- 0.04 g; D = 0.18 +/0 0.02 g; D + I = 0.42 +/- 0.05 g; D + T = 0.40 +/0 0.06 g) and total prostate weight (N = 0.24 +/- 0.02 g; D = 0.15 +/- 0.02 g; D + I = 0.24 +/- 0.05 g; D + T = 0.35 +/- 0.06 h). Testicular endogenous content of testosterone was restored after insulin treatment (N = 154 +/- 13 ng/testis; D = 41 +/- 5 ng/testis; D + I = 142 +/- 9 ng/testis), and significant improvements of serum testosterone levels were also achieved (N = 540 +/- 64 ng/100 ml; D = 238 +/- 37 ng/100 ml; D + I = 358 +/- 18 ng/100 ml). Prostate cytosol of streptozotocin-diabetic rats had strongly lowered capacity for 3H-R1881 binding compared with controls (94 and 12 fmol/mg protein, respectively). Testosterone treatment produced a 3.3-fold improvement of this lowered value, whereas the increment seen with insulin was less (1.5-fold). It is emphasized that some of the improvements caused by insulin replacement therapy in diabetic animals are due to the partial restoration of testosterone secretion. Thus, the combined actions of insulin and testosterone (instead of insulin alone) seem to be of major importance in the maintenance and regulation of accessory sex glands function.

Topics: Animals; Body Weight; Cytosol; Diabetes Mellitus, Experimental; Epididymis; Estrenes; Insulin, Long-Acting; Male; Metribolone; Organ Size; Prostate; Rats; Receptors, Androgen; Receptors, Steroid; Testis; Testosterone; Testosterone Congeners