FURTHER STUDIES ON THE UPTAKE OF ANDROGEN BY SOME ORGANS OF THE MALE RAT

1970 ◽  
Vol 63 (3) ◽  
pp. 489-498 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Muscle Tissue ◽  
Specific Activity ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Ventral Prostate ◽  
Supernatant Fraction ◽  
Male Rat

ABSTRACT [1,2-3H]Testosterone with a specific activity of 42.3 Ci/mmole was injected intramuscularly to adult castrated male rats. There was a selective uptake of radioactivity by the prostate, where a high and prolonged accumulation of radioactive material was found, in contrast to the much lower uptake by muscle tissue. The influence of castration on the uptake was investigated. In the ventral prostate, the uptake was 205% higher in animals castrated 24 h previously than in non-castrated animals. The corresponding values for the lateral prostate, the coagulating glands and the seminal vesicles were 120%, 165% and 213% respectively. The uptake by the dorsal prostate was only about 23% higher one day after orchidectomy. The uptake by muscle was apparently not influenced by castration. Following homogenization of the coagulating glands and the dorsal and ventral prostate, some of the radioactivity in the 105 000 × g supernatant fraction 1 h after the administration of [1,2-3H] testosterone in vivo was associated with macromolecules. In the lateral prostate an interaction between radioactive material and soluble macromolecules was only found in vitro.

METABOLISM IN VIVO OF [3H] ANDROSTENEDIONE AND [3H] TESTOSTERONE BY ANDROGEN DEPENDENT TISSUES

1970 ◽  
Vol 65 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Kjell J. Tveter ◽  
Asbjörn Aakvaag
Keyword(s):  
Intramuscular Injection ◽  
Total Activity ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Ventral Prostate ◽  
Supernatant Fraction ◽  
Rectus Abdominis Muscle ◽  
Main Metabolite

ABSTRACT The radioactive material present in the different prostatic lobes and the seminal vesicles was isolated and identified after intramuscular injection of [1,2-3H] testosterone to adult castrated male rats. 5α-Dihydrotestosterone was the main metabolite, representing 70, 72, 49, 56 and 70%, respectively, of the total activity in the ventral, dorsal and lateral prostate, the coagulating glands and the seminal vesicles one hour after the administration of hormone. The corresponding values for unchanged [3H] testosterone were 16, 6.4, 23, 6 and 15%, respectively. In rectus abdominis muscle less than 0.3% was 5α-dihydrotestosterone, while 37% represented unconverted [3H] testosterone. Of the activity in liver, [3H]-testosterone accounted for 0.2%, whereas less than 0.1% was 5α-dihydrotestosterone. One hour after administration of [1,2-3H] androst-4-ene-3,17-dione to adult castrated rats, the uptake of radioactivity in the ventral prostate was about 2.7 times higher than in skeletal muscle. In the ventral prostate, 32% of the total activity present at this time was represented by 5α-dihydrotestosterone, while 3.5% was unmetabolized [3H] androstenedione. The corresponding values for the seminal vesicles were 24 and 3.7%, respectively. In the 105 000 × g supernatant fraction of homogenized ventral prostate tissue, part of the radioactivity was associated with soluble macromolecules one hour after the administration of [3H]-androstenedione.

AN AUTORADIOGRAPHIC STUDY ON THE LOCALIZATION OF ANDROGEN IN THE PROSTATE GLAND AND THE SEMINAL VESICLES OF THE MALE RAT

1970 ◽  
Vol 63 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Epithelial Cells ◽  
Prostate Gland ◽  
Autoradiographic Study ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Male Rat ◽  
Selective Localization ◽  
Qualitative Pattern

ABSTRACT The distribution of radioactive material in the prostate gland and the seminal vesicles has been studied by autoradiography after intramuscular administration of [1,2-3H] testosterone in vivo to adult castrated male rats. Positive autoradiographs were obtained from 7½ min to 8 h after the administration. As early as after 15 min, there appeared to be a selective localization of radioactivity in the epithelial cells, with much of the labelling associated with the nuclei; the stromal labelling was markedly less. This picture was even more significant ½, 1 and 2 h after the injection, when the autoradiographs demonstrated a preferential labelling of the nuclei of the epithelial cells. A distinct labelling of the epithelial cells was also found 8 h after the injection. The same qualitative pattern of distribution of radioactivity was seen in the four prostatic lobes and the seminal vesicles. No significant labelling of the secretions in the glandular lumina was observed.

Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver

1984 ◽  
Vol 247 (3) ◽  
pp. G226-G230
Author(s):  
R. B. Kirkpatrick ◽  
B. G. Kraft
Keyword(s):  
Bile Acid ◽  
Specific Activity ◽  
Male Rats ◽  
Male Rat ◽  
Estrogen Metabolism ◽  
Normal Male ◽  
Activity Levels ◽  
Receptor Kinetics ◽  
Streptozotocin Induced Diabetes

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.

Quantification of the Uncertainties in Extrapolating From In Vitro Androgen Receptor Antagonism to In Vivo Hershberger Assay Endpoints and Adverse Reproductive Development in Male Rats

2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Adverse Outcome ◽  
In Utero ◽  
Male Rats ◽  
Male Rat ◽  
Rat Offspring ◽  
Hershberger Assay ◽  
Key Events

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of < 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.

DISTRIBUTION OF MALE AND FEMALE STEROID SEX HORMONES IN SOME ORGANS OF THE MALE RAT

1970 ◽  
Vol 65 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Skeletal Muscle ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Liquid Scintillation ◽  
Specific Activity ◽  
Seminal Vesicles ◽  
Anterior Pituitary Gland ◽  
Male Rats ◽  
Male Rat ◽  
Accessory Sex Organs

ABSTRACT [6,7-3H] 17β-Oestradiol with a specific activity of 42.4 Ci/mmole was injected intramuscularly into three to four month old male rats, castrated three days previously. The radioactivity in liver, skeletal muscle, blood, the anterior pituitary gland, the seminal vesicles and in the different prostatic lobes was measured by liquid scintillation counting at different intervals after the administration. A high and prolonged uptake of radioactivity was found in the anterior pituitary gland. The uptake by the accessory sex organs was much lower, but significantly higher than that by skeletal muscle. The uptake by the prostate and the seminal vesicles in castrated animals was similar to that in non-castrated animals. The pattern of radioactivity uptake in the anterior pituitary gland of castrated male rats given [3H] testosterone was distinctly different from that after administration of [3H] 17β-oestradiol. There was a rapid elimination of radioactivity from the adenohypophysis after the administration of [3H] testosterone.

UPTAKE AND BINDING OF 5α-DIHYDROTESTOSTERONE IN RAT VENTRAL PROSTATE IN VIVO

1971 ◽  
Vol 67 (2) ◽  
pp. 384-392 ◽  
Author(s):  
Vidar Hansson ◽  
Kjell J. Tveter ◽  
Arne Attramadal
Keyword(s):  
Muscle Tissue ◽  
Intravenous Administration ◽  
Male Rats ◽  
Ventral Prostate ◽  
Long Period ◽  
Rat Ventral Prostate

ABSTRACT Following the intravenous administration of [3H] 5α-dihydrotestosterone to adult castrated male rats, the highest uptake of radioactivity was found in the liver and the prostate, in contrast to the much lower uptake in muscle tissue and blood. The results were essentially the same as after the administration of [3H] testosterone. The uptake in the prostate was, however, retained for a long period of time, while the concentration of radioactivity in the liver decreased rapidly after administration and was already lower than that in the prostate after 30 minutes. After the injection of [3H] 5α-dihydrotestosterone in vivo, the labelled adrogen was found to be associated with macromolecules in the prostatic cytosol and with salt extractable nuclear macromolecules.

THE EFFECT OF 2-BROMO-α-ERGOCRYPTINE (CB154) ADMINISTRATION ON THE HORMONE LEVELS, ORGAN WEIGHTS, PROSTATIC MORPHOLOGY AND ZINC CONCENTRATIONS IN THE MALE RAT

1976 ◽  
Vol 83 (1) ◽  
pp. 211-224 ◽  
Author(s):  
M. E. Harper ◽  
V. Danutra ◽  
J. A. Chandler ◽  
K. Griffiths
Keyword(s):  
Prostatic Tissue ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Cell Organelles ◽  
Adenyl Cyclase Activity ◽  
Zinc Concentrations ◽  
High Concentrations

ABSTRACT 2-Bromo-α-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.

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.

Anti-idiotypic antibody as an oestrogen mimetic in vivo: stimulation of creatine kinase specific activity in rat animal models

1996 ◽  
Vol 149 (2) ◽  
pp. 305-312 ◽  
Author(s):  
D Sömjen ◽  
Y Amir-Zaltsman ◽  
G Mor ◽  
B Gayer ◽  
S Lichter ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Animal Models ◽  
Specific Activity ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Diaphyseal Bone ◽  
Idiotypic Antibody ◽  
Stimulation Of

Abstract Previous studies indicated that the anti-idiotypic antibody (clone 1D5) significantly increased the specific activity of creatine kinase (CK) activity in the rat uterus, and in vitro in skeletal cells capable of responding to oestradiol (E2), suggesting that the antibody has oestrogenic-like activity. Moreover, the F(ab′)2 dimer of clone 1D5 acted like an antagonist and completely inhibited the increase in CK specific activity by either E2 or clone 1D5 in these skeletal cells. In the present study, we examined the in vivo effects of clone 1D5 and its proteolytic fragment, the F(ab′)2 dimer, E2 and dihydrotestosterone (DHT) on CK specific activity in the epiphyseal cartilage, diaphyseal bone, uterus, prostate, thymus and pituitary of immature or gonadectomized female and male rat animal models. In the intact immature animals, clone 1D5 caused an increase in CK in all organs of the female except in the pituitary. In the diaphyseal bone and prostate of male rats there was no stimulation by 1D5. The CK response in the uterus, epiphysis, and diaphysis of immature female rats was dose-dependent and was blocked by either the anti-oestrogen tamoxifen or the F(ab′)2 dimer of clone 1D5. E2, DHT, as well as clone 1D5, stimulated CK specific activity in both the diaphysis and epiphysis of ovariectomized female and castrated male rats, whereas sex specificity in the CK response was observed also in the uterus and the prostate of gonadectomized animals. Collectively, these results suggest that, as in cell culture, an intact antibody is necessary for the observed stimulation of CK specific activity and the F(ab′)2 dimer can act as an antagonist. Furthermore, the observed biological effects of clone 1D5 which are absolutely parallel to E2, imply that the anti-idiotypic antibody is able to penetrate the cell and reach the nuclear oestrogen receptor and transduces a signal to the nucleus, by as yet uncharacterized mechanisms. Journal of Endocrinology (1996) 149, 305–312

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