METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1973 ◽  
Vol 73 (2) ◽  
pp. 407-416 ◽  
Author(s):  
H. Becker ◽  
E. Grabosch ◽  
C. Hoffmann ◽  
K. D. Voigt
Keyword(s):  
Chemical Structure ◽  
Total Radioactivity ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Receptor Protein ◽  
Hydroxy Derivative ◽  
Adult Rats ◽  
Peripheral Muscle ◽  
Capacity Limit ◽  
Target Organs

ABSTRACT Either 1.3 μg [5,6-3H]5α-androstane-3,17-dione (27 Ci/mm), or 12 μg respectively 0.8μg [5,6-3H]5α-androstane-3α,17β-diol (3 Ci/mm), or 12μg respectively 0.8 μg ([5,6-3H]5α-androstane-3β,17β-diol (3 Ci/mm) were administered intravenously to normal adult rats on days 0, 3 and 12 after castration. 30 min after the injection the animals were sacrificed. Total radioactivity counting was performed on aliquots of extracts of blood, peripheral muscle, prostate and seminal vesicles. In the remaining extracts the steroids were isolated by repeated chromatography with and without derivative formation. The following results should be mentioned: 1. Compared to muscle an accumulation of radioactivity is found especially in the prostate on day 3 after castration. 2. Regarding the unconjugated metabolites in plasma no measurable interconversion of both diols has been observed, whereas androstanedione was efficiently metabolised to both diols and to androsterone. In muscle a substantial oxydation of both diols to the corresponding 17-keto-3-hydroxy derivative occurred. 3. In both target organs the three androgens were converted to 5α-DHT2) though in varying amounts. 4. From a calculation of the data available in both target organs a figure of 200 to 300 pg 5α-DHT/mg DNA has been obtained which is regarded as the receptor protein capacity limit. The influence of castration, of enzyme activities and of the chemical structure of the androgens administered on this figure is discussed.

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1972 ◽  
Vol 69 (1) ◽  
pp. 153-164 ◽  
Author(s):  
L. Buric ◽  
H. Becker ◽  
C. Petersen ◽  
K. D. Voigt
Keyword(s):  
Skeletal Muscle ◽  
Adult Male ◽  
Mode Of Action ◽  
Total Radioactivity ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Peripheral Muscle ◽  
Target Organs ◽  
Accessory Sex Organs ◽  
Testosterone Administration

ABSTRACT Either 0.7 μg [1,2-3H] testosterone* (51 Ci/mm) or 0.8 μg [1,2-3H] 5α-dihydrotestosterone (44 Ci/mm) was administered intravenously to normal adult male rats 3, 7, and 12 days after castration. 30 min after the injection, the animals were sacrificed. Total radioactivity counting was performed on aliquots of extracts of blood, peripheral muscle, prostates and seminal vesicles. In a first TCL the extracts were separated into five fractions. Further purification by acetylation and repeated chromatographic procedures revealed, that fraction C consisted of about 90 % of testosterone, fraction D of varying amounts of 5α- and 5β-DHT, fraction E of androstanedione and androstenedione, and fraction B mainly of androstanediols. The following results should be mentioned: 1. The radioactivity uptake by the accessory sex organs was significantly higher than that of skeletal muscle. The highest values were found on day 3 after castration. 5α-DHT under all conditions produced higher concentrations in the target tissues than testosterone, whereas in skeletal muscle the opposite was found. 2. After testosterone administration testosterone was very efficiently converted to 5α-DHT in target organs. Nevertheless substantial amounts of testosterone and of androstanedione and androstanediols are present. In blood, however, only small amounts of labelled 5α-DHT were found. After 5α-DHT administration, in target organs, 5α-DHT was converted to androstanedione and androstanediols up to about 20%. In blood the bulk of radioactivity was related to the androstanediol fraction. No conclusion therefore can be drawn from the data obtained in blood on the metabolic events occurring in the target organs. 3. The sequence of metabolic events in the target tissues supports the concept of a preferred 17-hydroxy pathway and a lack of 5β-reductase.

EFFECTS OF TESTOSTERONE MEDIATED OR MODULATED BY PITUITARY FACTORS

1975 ◽  
Vol 67 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. DE MOOR ◽  
M. ADAM-HEYLEN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN
Keyword(s):  
Body Weight ◽  
Testosterone Propionate ◽  
Total Body Weight ◽  
Seminal Vesicles ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Adult Rats ◽  
Organ Weights ◽  
Total Body

SUMMARY Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.

EFFECTS OF FOLLICLE-STIMULATING HORMONE AND LUTEINIZING HORMONE ON PLASMA TESTOSTERONE LEVELS IN HYPOPHYSECTOMIZED AND IN INTACT IMMATURE AND ADULT MALE RATS

1974 ◽  
Vol 61 (2) ◽  
pp. 193-198 ◽  
Author(s):  
S. EL SAFOURY ◽  
A. BARTKE
Keyword(s):  
Luteinizing Hormone ◽  
Adult Male ◽  
Follicle Stimulating Hormone ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Adult Rats ◽  
Testosterone Levels ◽  
Hypophysectomized Rats ◽  
Stimulating Hormone

SUMMARY The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on plasma testosterone levels were examined in hypophysectomized and in intact immature and adult male rats. The animals were injected with saline, LH, FSH, or both gonadotrophins twice daily for 3·5 days and were killed 3 h after the last injection. Plasma testosterone levels were measured by radioimmunoassay. In immature hypophysectomized rats, plasma testosterone levels were not changed by treatment with LH, FSH or LH plus FSH. The weight of the testes and of the seminal vesicles was increased only in animals injected with both LH and FSH. In adult hypophysectomized rats, LH caused the expected increase in plasma testosterone levels, while FSH injected alone had no effect. Plasma testosterone levels in rats treated with 5 μg LH and 20 μg FSH were significantly greater than those in animals given 5 μg LH alone. However, the same dose of FSH did not potentiate the action of 25 μg LH on plasma testosterone levels. In adult hypophysectomized rats the weight of testes was not affected by any of the treatments. The weight of the seminal vesicles was increased by the higher dose of LH and addition of FSH caused no further increase. In intact immature and adult rats plasma testosterone levels and the weight of testes were not changed by any of the treatments. Seminal vesicle weight was increased only in adult rats treated with the higher dose of LH together with FSH. The results demonstrate that FSH potentiates the action of low doses of LH on plasma testosterone levels in adult hypophysectomized rats and suggest that FSH may be involved in the regulation of androgen secretion by the rat testis.

Urethral plug-a new secondary male sex characteristic in rat and other rodents

1982 ◽  
Vol 16 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Ivo Kunstýř ◽  
Werner Küpper ◽  
Herwig Weisser ◽  
Susanne Naumann ◽  
Claus Messow
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Adult Male ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Average Weight ◽  
Adult Rats ◽  
Vaginal Plug ◽  
Male Sex ◽  
Proximal Urethra

The plug is an eosinophilic mass, partly homogenous and partly porous, filling the proximal urethra in rats and occasionally extending into the bladder. Its average weight in 131 adult rats was 0·063 g. These plugs are normally present in the urethra of adult male rats, and this seems to be the case for all laboratory Muridae and Cavidae. The absence of a plug in an adult male may be a sign of abnormality associated with failing health. There is an interesting similarity between the amino acid composition of the content of seminal vesicles, that of the urethral plug, and that of the copulatory vaginal plug in female rodents.

BINDING AND METABOLISM OF 5α-ANDROSTANE-3α,17β-DIOL AND OF 5α-ANDROSTANE-3β,17β-DIOL IN THE PROSTATE, SEMINAL VESICLES AND PLASMA OF MALE RATS: STUDIES IN VIVO AND IN VITRO

1975 ◽  
Vol 64 (3) ◽  
pp. 529-538 ◽  
Author(s):  
M. KRIEG ◽  
H.-J. HORST ◽  
M.-L. STERBA
Keyword(s):  
Skeletal Muscle ◽  
Specific Binding ◽  
Biological Effects ◽  
Sucrose Density Gradient ◽  
Total Radioactivity ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Cytosol Fraction

SUMMARY Binding of 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) in vivo and in vitro to the 100000 g cytosol fraction of the rat prostate and seminal vesicles as well as to plasma was studied by agargel electrophoresis and sucrose density gradient ultracentrifugation and the results compared with the corresponding findings for 5α-dihydrotestosterone (5α-DHT). The metabolism of 3α-diol and 3β-diol was also investigated by thin-layer chromatography. The following results were obtained: (1) A specific binding of 3α-diol and 3β-diol by the cytosols could not be demonstrated in vitro, while 5α-DHT was specifically bound. (2) In plasma, 3α-diol was extensively bound, 3β-diol less extensively bound, while 5α-DHT remained unbound. (3) After intravenous injection of 3α-diol, specifically bound radioactivity, increasing within 30 min, was found in the prostate cytosol, while after 3β-diol injection no binding occurred. (4) Parallel to the increased binding, the total radioactivity in the prostate accumulated within 30 min after 3α-diol injection, the uptake being 5·3 times higher than in skeletal muscle. However after 3β-diol injection, total radioactivity decreased in the prostate within 30 min, the uptake being only 1·5 times higher than in skeletal muscle. (5) One minute after injection of 3α-diol, 53% of the extracted radioactivity in the prostate had been converted to 5α-DHT, this increased within 30 min to 81%. Thirty minutes after the injection of 3β-diol, about 32% of the extracted radioactivity in the prostate had been converted to 5α-DHT. (6) From the in-vivo and in-vitro experiments it was concluded that 3α-diol exerts its biological effects mainly by its conversion into 5α-DHT.

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1975 ◽  
Vol 80 (3) ◽  
pp. 592-602 ◽  
Author(s):  
R. Szalay ◽  
M. Krieg ◽  
H. Schmidt ◽  
K. D. Voigt
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Mode Of Action ◽  
Cyproterone Acetate ◽  
Biologically Active ◽  
Male Rats ◽  
Adult Rats ◽  
Target Organs ◽  
Layer Chromatography

ABSTRACT In order to get more information on the mode of action of anti-androgens, two series with low but biologically active doses of cyproterone acetate were started. In the first experiments 12 μg of [3H] cyproterone acetate was injected intravenously into adult rats castrated 3 days before treatment. Thirty min after injection the radioactivity uptake in the target organs and other tissues was measured. The metabolites were separated by thin layer chromatography. A large pool of radioactivity could be shown in the liver. Thin layer chromatography revealed that in this pool cyproterone acetate had been converted by more than 80% to one metabolite. In blood plasma, too, the metabolite accounted for the major part of radioactivity. When compared to skeletal muscle, the prostate, seminal vesicles, and m. bulbocavernosus and m. levator ani accumulated more radioactivity. Within 30 min unchanged cyproterone acetate was retained selectively thus showing its relative high affinity to target organs. In a second experimental series, adult castrated male rats were given 10 μg of cyproterone acetate intravenously 30 min before the injection of [3H] testosterone or [3H]5α-dihydrotestosterone. Under this condition androgen uptake in target tissues was reduced to about 70 % of the control values. The data parallel the results of in vivo studies on cytosol receptor displacement of androgens by cyproterone acetate. In agreement with previous investigators no significant influence of the anti-androgen on androgen metabolism was observed. The importance of the findings concerning the mode of anti-androgen action is discussed.

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUE OF MALE RATS

1973 ◽  
Vol 73 (3) ◽  
pp. 599-611 ◽  
Author(s):  
H. Schmidt ◽  
O. Giba-Tziampiri ◽  
G. v. Rotteck ◽  
K. D. Voigt
Keyword(s):  
Cell Proliferation ◽  
Cell Metabolism ◽  
Cellular Level ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nucleic Acid Content ◽  
Target Tissue ◽  
Proliferative Effect ◽  
Target Organs

ABSTRACT The effects of 5α-androstane-3,17-dione2), of 5α-androstane-3β,17β-diol and of 5α-androstane-3α,17β-diol on protein and nucleic acid content as well as on the activities of some enzymes have been studied in the ventral prostate and the seminal vesicles of immature castrated rats. The androgens were administered in doses of 0.1 mg or 1 mg three times at 24 h intervals respectively, and the animals were sacrificed 24 h after the last injection. In accordance with the literature 5α-androstane-3,17-dione had a distinctly greater effect on the ventral prostates than on the seminal vesicles. Furthermore it could be demonstrated that in seminal vesicles this androgen had no effect on cell proliferation, whereas cell metabolism was slightly stimulated. The lack of cell proliferation in seminal vesicles is probably due to a smaller conversion of the steroid to 5α-dihydrotestosterone, i.e. to a weaker activity of the 17β-oxidoreductase in this target organ. The 5α-androstane-3β,17β-diol as well as the 5α-androstane-3α,17β-diol had a marked effect on DNA increase, comparable to that of 5α-dihydrotestosterone in both target organs. In the case of the 5α-androstane-3α,17β-diol this effect could be due to its high conversion rate to 5α-dihydrotestosterone. However, this is not the case for the 5α-androstane-3β,17β-diol. It seems possible that the 3β-hydroxy group of an androgen also exerts a cell proliferative effect. Concerning stimulation of cell metabolism in both target organs a greater effect was found after the administration of 5α-androstane-3α,17β-diol. This again leads to the conclusion that there are different sites of androgen action at the cellular level.

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt
Keyword(s):  
Cell Proliferation ◽  
Cell Metabolism ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nucleic Acid Content ◽  
The Difference ◽  
Independent Effects ◽  
Sites Of Action ◽  
Peripheral Metabolism

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

Abstract 403: Renal Denervation Reveals Renal Sympathetic Activation in Adult Rats Exposed to Early Life Stress

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Analia S Loria ◽  
Michael W Brands ◽  
David M Pollock ◽  
Jennifer S Pollock
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Renal Denervation ◽  
Early Life Stress ◽  
Male Rats ◽  
Renal Nerves ◽  
Adult Rats ◽  
Baseline Conditions ◽  
Control Sham ◽  
Renal Sympathetic

We previously reported that maternal separation (MS), a model of early life stress, does not modify baseline blood pressure in adult rats, but increases sensitivity to hypertensive stimuli. Under baseline conditions, adult male rats exposed to MS have significantly reduced glomerular filtration rate (GFR). Acute phenylephrine-induced reductions in renal blood flow is significantly attenuated in rats exposed to MS compared to control rats. Furthermore, norephinephrine (NE) content was increased in renal cortex of MS rats compared to control rats (p<0.05). These data indicate that MS induces increased renal sympathetic outflow. Thus, we hypothesized that renal denervation will normalize GFR in rats exposed to MS. Male WKY rat pups were separated from their mothers for 3 hrs/day during the morning hours from day 2 to 14 of life. Male non-separated littermates served as control rats. Experiments were performed in 300-320 g adult rats. Denervation (DnX) was performed mechanically stripping all visible renal nerves followed by topical phenol (10%) on the renal artery. Control-sham, MS-sham, control-DnX, and MS-DnX rats were instrumented with catheters in the femoral vein and abdominal aorta. Rats were placed in metabolic cages, connected to swivels, and allowed to recover for 4-5 days. Sodium intake was clamped at 2.8 mEq/day in both groups by combining sodium deficient diet and 24 hr/day 0.9% iv saline infusion (20 ml/day). GFR was determined by plasma clearance of [125I]iothalamate in the conscious state. During baseline conditions, MAP was not different between control-sham and MS-sham rats (99±4 vs 97±2 mmHg, respectively). MAP was reduced in both control-DnX and MS-DnX rats (91±2 mmHg and 83±3 mmHg, p<0.05, respectively) compared with the respective sham group. The reduction in MAP tended to be greater in MS than in control rats (-9±1 and -14±2 mmHg, p=0.074). DnX did not modify GFR in control rats (sham: 3.1±0.1 ml/min vs DnX: 3.5±0.4 ml/min). However, DnX significantly increased GFR in rats exposed to MS (sham: 2.4±0.2 ml/min vs DnX: 3.8±0.4 ml/min, p<0.05). These data support our hypothesis that MS induces increased renal sympathetic tone to reduce GFR in MS male rats, and may contribute to the exacerbated response to hypertensive stimuli observed in MS rats.

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