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

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.

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.


1970 ◽  
Vol 65 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Kjell J. Tveter

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.


1975 ◽  
Vol 64 (3) ◽  
pp. 529-538 ◽  
Author(s):  
M. KRIEG ◽  
H.-J. HORST ◽  
M.-L. STERBA

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.


1983 ◽  
Vol 96 (2) ◽  
pp. 321-327 ◽  
Author(s):  
N. M. Biswas ◽  
P. K. Ghosh ◽  
K. K. Ghosh ◽  
O. W. Neuhaus

Adult male rats were given injections of oestradiol-17β (50 μg/100 g body wt per day) for 7 days. When they were killed 14 days after the last injection, serum levels of gonadotrophins and testosterone and weights of accessory sex organs were less, testicular 17β-hydroxysteroid dehydrogenase 17β-HSD activity was suppressed and spermatogenesis was inhibited. Administration of α2u-globulin (1·5 mg/day) for 14 days to oestrogen-treated rats and for 10 days to control rats resulted in increased concentrations of gonadotrophins and testosterone in the serum. Accessory sex organ weight and spermatogenesis appeared to be normal while 17β-HSD activity increased in oestrogen-treated rats after treatment with α2u-globulin. It was concluded that α2u-globulin has an effect on testicular function in oestrogenized rats by inducing gonadotrophin and testosterone synthesis.


1974 ◽  
Vol 61 (2) ◽  
pp. 193-198 ◽  
Author(s):  
S. EL SAFOURY ◽  
A. BARTKE

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.


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.


1982 ◽  
Vol 16 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Ivo Kunstýř ◽  
Werner Küpper ◽  
Herwig Weisser ◽  
Susanne Naumann ◽  
Claus Messow

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.


1967 ◽  
Vol 56 (2) ◽  
pp. 221-224 ◽  
Author(s):  
A. P. Baker ◽  
F. Bergman ◽  
B. Josefsson ◽  
K. G. Paul

ABSTRACT Castrated, adult male rats were given a long-acting androgen in doses that caused a rapid growth of the anterior prostate lobes, the seminal vesicles, and the levator ani muscle. There was no decrease in the number of mast cells, and no increase in the number of eosinophils.


1978 ◽  
Vol 176 (3) ◽  
pp. 677-681 ◽  
Author(s):  
Peggy R. Borum

Diabetes, starvation and various hormonal treatments are known to alter drastically carnitine concentrations in the body. Before the mechanisms controlling carnitine metabolism could be determined, it was necessary to establish normal carnitine concentrations in both sexes at different ages. Carnitine was assayed in plasma, liver, heart and skeletal muscle of rats from birth to weaning. The plasma carnitine increased rapidly during the first 2 days after birth. Carnitine in both heart and skeletal muscle increased, whereas liver concentrations declined during the first week of life. A carnitine-free diet containing sufficient precursors for carnitine biosynthesis was fed to weanling rats. Groups of ten male and ten female rats were killed each week for 10 consecutive weeks. Carnitine was determined in plasma, liver, heart, skeletal muscle, urine and epididymis in the male. There was no difference in carnitine concentrations between the sexes at weaning. Plasma, heart and muscle concentrations were higher in adult male rats than in adult females. However, liver carnitine and urinary carnitine concentrations were higher in adult female than in adult male rats. The epididymal carnitine concentration increased very rapidly during 50 to 70 days of age and the differences in carnitine concentrations between the sexes also became apparent during this time. Thus both the age and the sex of the human subject or experimental animal must be considered when investigating carnitine metabolism.


1987 ◽  
Vol 113 (1) ◽  
pp. 51-55 ◽  
Author(s):  
F. T. A. Fitzpatrick ◽  
B. D. Greenstein

ABSTRACT The effects of several steroids on the regenerating thymus in ageing male rats have been studied. Rats aged from 12 to 15 months were orchidectomized and 7 days later implanted s.c. with silicone elastomer tubing containing 25 mg testosterone, 5α-dihydrotestosterone (DHT), oestradiol, progesterone or corticosterone. One group of rats received an empty implant. Thirty days later the rats were killed and the thymus, spleen, ventral prostate and seminal vesicles weighed and retained for histology. Whole blood was taken for total and differential white cell counts; plasma was prepared for radioimmunoassay of testosterone, oestradiol, progesterone and corticosterone. After orchidectomy only, a multilobular thymus was present, and histologically the tissue appeared healthy. In testosterone- and oestradiol-treated rats, thymus weight was reduced to about 50% of that in untreated animals. Histologically, much of the thymus taken at autopsy was fat and what remained was poorly organized and contained a much lower density of thymocytes. The total white cell count was significantly reduced in these animals, the effect appearing to be predominantly on lymphocytes. Although treatment with DHT also resulted in a lower mean thymus weight than that of orchidectomized animals, histologically the tissue appeared similar to that of the untreated castrated animals. In rats treated with DHT, the total white cell count was significantly higher than in testosterone-implanted rats. Both progesterone and corticosterone implants resulted in significantly smaller mean thymus weights, although these steroids were not as potent as testosterone or oestradiol. Corticosterone, but not progesterone, appeared to cause a significant reduction in circulating lymphocytes. Dihydrotestosterone possessed only half the potency of testosterone in restoring the weights of the accessory sex organs. Serum concentrations of testosterone in orchidectomized old rats were 0·33 ± 0·02 nmol/l and in testosterone-implanted rats 4·8 ± 0·4 nmol/l. These results raise the possibility that testosterone and oestradiol may have caused atrophy of the thymus, while DHT may have retarded regeneration of the thymus without any atrophic effect. It remains to be seen whether the different responses between testosterone and DHT, in both the thymus and accessory sex organs, are due to differences in intrinsic action or differences in the metabolism of the steroids. J. Endocr. (1987) 113, 51–55


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