The Radioautographic Localization of Exogenous Tritiated Dihydrotestosterone, Testosterone and Oestradiol in the Target Organs of Female and Male Rats

2015 ◽  
pp. 208-214 ◽  
Author(s):  
P. Tuohimaa
Keyword(s):  

1966 ◽  
Vol 34 (1) ◽  
pp. 117-123 ◽  
Author(s):  
R. L. MORRISON ◽  
D. C. JOHNSON

SUMMARY Male rats were castrated on the day of birth and 5 days later half were given 2·5 mg. testosterone propionate (TP) subcutaneously (androgenization). When 30 days old, single animals were treated with graded doses of TP for 10 days. At the same time 57 males were united in parabiosis with normal intact males, and treated for 10 days with androgen. Androgenization resulted in increased sensitivity of the accessory sex organs to subsequent treatment with TP. Also, the excessive secretion of gonadotrophin by the castrated animals, as measured by androgen production in intact parabiotic partners, was more effectively inhibited by TP in androgenized than in non-androgenized males. The results are consistent with the interpretation that early androgen treatment sensitizes both the male target organs and the hypothalamo-hypophysial system to androgen.



1984 ◽  
Vol 100 (2) ◽  
pp. 245-248 ◽  
Author(s):  
A. Mode ◽  
J.-Å. Gustafsson ◽  
P. Södersten ◽  
P. Eneroth

ABSTRACT Masculine sexual behaviour was induced in castrated sexually inactive but experienced male rats by testosterone-filled constant-release implants or daily injections of the synthetic androgen 17β-hydroxy-17α-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R 1881), which resists metabolism by target organs. Feminization of the hepatic androgen metabolism by subcutaneous implantation of osmotic minipumps, which delivered a constant amount of human GH, did not affect the behavioural response of castrated rats to testosterone. Testosterone implants were only minimally effective in inducing male behaviour in ovariectomized female rats, but R 1881 was as effective in stimulating male behaviour in females as in males. Testosterone-treated but not R 1881-treated females showed pronounced female sexual behaviour in response to progesterone treatment despite the absence of measureable amounts of oestradiol-17β in peripheral blood. The results provide evidence that masculine sexual behaviour can be activated by an androgen in the absence of oestrogenic stimulation and suggest that the sex difference in the behavioural response to testosterone may be due to a sex difference in the metabolism of androgens by the brain. J. Endocr. (1984) 100, 245–248



1967 ◽  
Vol 54 (3) ◽  
pp. 557-567 ◽  
Author(s):  
K.-O. Mosebach ◽  
H. Jühe ◽  
W. Dirscherl

ABSTRACT Over a period of 2 hours the distribution and the specific activities of 14C (dpm/mg C) in organs of immature male Sprague-Dawley rats were studied after infusion of testosterone-4-14C. Only in liver, adrenals, kidneys and lungs we found specific activities essentially higher than those of the blood. The values of testis, seminal vesicles, prostata, epididymis and penis were similar to blood. Corresponding to former experiments using injection technique the more physiological infusion technique did not show any accumulation of radioactivity in the target organs too. On the contrary the specific activity of the seminal vesicle secretion was clearly higher than those of the residue organ and the blood. In adrenals medulla contained more radioactivity than cortex, demonstrated by 3 different methods (combustion, extraction and histoautoradiography). The distributions of progesterone-4-14C and oestradiol-4-14C after infusion in immature male rats were similar to those of testosterone-4-14C. The latter did not show a striking affinity for uterus, vagina and ovaries after infusion into female immature rats.



1972 ◽  
Vol 69 (1) ◽  
pp. 153-164 ◽  
Author(s):  
L. Buric ◽  
H. Becker ◽  
C. Petersen ◽  
K. D. Voigt

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.



1977 ◽  
Vol 84 (4) ◽  
pp. 813-828 ◽  
Author(s):  
Rachel Hamburger-Bar ◽  
Henk Rigter

ABSTRACT The effects of androgens on the maintenance and restoration of sexual behaviour (mounts, intromissions and ejaculations) of castrated male rats were studied. In the maintenance study the rats were treated during 5 weeks, starting one day following castration. Testosterone propionate maintained sexual behaviour at an almost normal level. The androgenoestrogen intermediate 19-hydroxytestosterone propionate was unable to prevent the decline in the number of ejaculations over the weeks although this hormone maintained the post-ejaculatory refractory period in those rats that ejaculated and also maintained normal sexual latencies. In the restoration study administration of testosterone propionate during 7 weeks to long-term castrated rats restored sexual behaviour to normal. 19-Hydroxytestosterone propionate treated rats displayed mounts but no other signs of sexual behaviour. The 5α-reduced androgen dihydrotestosterone propionate did not restore sexual behaviour. Testosterone propionate and dihydrotestosterone propionate stimulated peripheral target organs; 19-hydroxytestosterone propionate was ineffective in this respect. It has been suggested that testosterone might stimulate sexual behaviour in rats in two ways, i. e., via its aromatization to oestradiol in the brain, and by stimulating growth of peripheral tissues via its 5α-reduction to dihydrotestosterone. In support for this view we have found that the combination of 19-hydroxytestosterone propionate and dihydrotestosterone propionate was effective in restoring the full pattern of sexual behaviour in castrated male rats.



1975 ◽  
Vol 80 (3) ◽  
pp. 592-602 ◽  
Author(s):  
R. Szalay ◽  
M. Krieg ◽  
H. Schmidt ◽  
K. D. Voigt

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.



2020 ◽  
pp. 43-44
Author(s):  
B.O. Kondratskyi ◽  
D.L. Kachmaryk ◽  
O.M. Panas ◽  
M.Y. Vynarchyk ◽  
O.G. Braginets

Objective. To investigate the morphological features of the internal organs of experimental animals and identify potential target organs with the introduction of ultra-high doses of the drug ALX-5 % and the drug with double the concentration of components ALX-2N. Materials and methods. The experiments were performed on outbred white male mice and outbred white male rats. Animals were administered ALX-5 % and ALX-2N solution. ALX-5 % protein-saline solution contains: donor albumin (5 %) pentatomic alcohol xylitol (5 %), alkalizing components – sodium lactate (1.9 %) and sodium bicarbonate (0.01 %), as well as sodium chloride (0.8 %), potassium chloride (0.03 %), calcium chloride (0.01 %). Theoretical osmolarity – 990 mOsm/l, pH – 6.2-7.4. The drug with double the concentration of ALX-2N contains all these components in double the concentration (osmolarity of the solution – 1980 mOsm/l). ALX-5 % was administered intraperitoneally multiple times at a dose of 174 ml/kg for mice and 90 ml/kg for rats. These doses are conditionally toxic, as these doses are the maximum that animals have been able to administer. Further increase in the volume of infusion solution was not allowed due to possible excessive hypervolemic effect. The ALX-2N solution was administered at a dose of 50 ml/kg. At the end of the experiment, histological preparations were prepared from the internal organs of animals, which were stained with hematoxylin and eosin and toluidine blue and studied under a light microscope. Results and discussion. It was found that when white mice and white rats were injected with the native protein-salt preparation ALX-5 % (osmolarity of the solution – 990 mOsm/l) in ultra-high doses (174 ml/kg for mice and 90 ml/kg for rats) the main target organs were the brain and lungs. Changes in other organs (kidneys, liver, pancreas, spleen, heart) are uncritical. With the introduction of concentrated drug ALX-2N (osmolarity of the solution – 1980 mOsm/l) at a dose of 50 ml/kg in addition to pronounced changes in the lungs and brain, dystrophic changes of heart and liver cells are observed. In all the study groups of animals accumulation of glycogen was observed, which is obviously due to administration of the high dose polyhydric alcohols xylitol and sodium lactate, a significant part of which is metabolized in the liver. Conclusions. According to the results of a comprehensive study of pharmaco-toxicological properties, it was found that the multicomponent protein-salt solution ALX-5 % may be suitable for further clinical study.



1973 ◽  
Vol 73 (2) ◽  
pp. 407-416 ◽  
Author(s):  
H. Becker ◽  
E. Grabosch ◽  
C. Hoffmann ◽  
K. D. Voigt

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.



1973 ◽  
Vol 73 (3) ◽  
pp. 599-611 ◽  
Author(s):  
H. Schmidt ◽  
O. Giba-Tziampiri ◽  
G. v. Rotteck ◽  
K. D. Voigt

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.



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