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

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.

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.


1972 ◽  
Vol 69 (2) ◽  
pp. 359-368 ◽  
Author(s):  
Lars-Eric Tisell

ABSTRACT The weight and histology of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles were studied in castrated non-adrenalectomized male rats after sixteen days of daily injections of testosterone propionate and in castrated adrenalectomized rats after daily injections of testosterone propionate alone or in combination with cortisone. Testosterone propionate was given in daily doses of 0.020 mg and cortisone in daily doses of 1 mg, 3 mg or 9 mg. Testosterone alone induced a less pronounced growth of the dorsolateral prostate, the coagulating glands and the seminal vesicles in castrated non-adrenalectomized than in castrated adrenalectomized rats, suggesting an inhibitory effect of adrenal steroids on the action of testosterone. Cortisone which has a weak androgenic effect when given alone, partially counteracted the testosterone induced growth of the accessory reproductive organs in castrated adrenalectomized rats.


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


1969 ◽  
Vol 62 (4) ◽  
pp. 694-710 ◽  
Author(s):  
Lars-Eric Tisell ◽  
Lennart Angervall

ABSTRACT The growth of the ventral and the dorsolateral prostate, the coagulating glands, seminal vesicles and levator ani muscle was studied in castrated male rats after fifteen days of daily injections with ACTH or insulin alone, or in combination. ACTH was given in a dose of 8 IU daily. Insulin was administered in increasing daily doses, i. e. regular insulin up to 8 IU and protamine zinc insulin up to 10 IU. After ACTH treatment there were variable histological signs of stimulation of the dorsolateral prostate, while the other accessory reproductive organs showed no response. Regular insulin produced no quantitative or morphological changes in the accessory reproductive organs, and no morphological signs of increased secretion of the adrenal steroids. Administration of ACTH and regular insulin in combination stimulated the growth of all the accessory reproductive organs. Protamine zinc insulin produced prolonged hypoglycaemia and morphological signs of increase secretion of adrenal steroids, thus the adrenals became enlarged and the thymus atrophic. Protamine zinc insulin stimulated growth of all the accessory reproductive organs, a stimulation which was further accentuated after combination with ACTH. Possible mechanisms for the action of insulin on the male accessory reproductive organs are discussed. The varying response of the different parts of the prostate and the seminal vesicles emphasizes the importance of the simultaneous examination of these organs.


1970 ◽  
Vol 65 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Kjell J. Tveter ◽  
Asbjörn Aakvaag

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.


2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Pankaj K. Sharma ◽  
H. Rehwani ◽  
A. K. Rai ◽  
R. S. Gupta ◽  
Y. P. Singh

Triphenylantimony(V) derivative,Ph3Sb(OPri)[SC6H4N:C(CH3)CH2C(O)CH3],1b, and the corresponding benzothiazoline ligand [1, 2],HNC6H4SC︹(CH3)CH2C(O)CH3,1a, have been tested for their effects on the reproductive system of male albino rats. The oral administration of both1aand1bat the dose level of 10 mg/rat/day produced significant reduction in the weights of testes, epididymides, seminal vesicles, and ventral prostate. Significant decrease in sperm motility as well as in sperm density resulted in 100% sterility. Significant (P<.01) alterations were also found in biochemical parameters of reproductive organs in treated male rats as compared to the control group. Production of preleptotene, pachytene, and secondary spermatocytes was decreased by 42%, 43%, 39%, and by 44%, 49%, 55% in the ligand,1a, and organoantimony(V) derivative,1b, treated rats, respectively. These results indicate that both compounds1aand1bare antispermatogenic in nature and on oral administration in male rats, and finally caused sterility. A comparison indicates that the organoantimony(V) derivative1bis more effective pertaining to its antispermatogenic activity than the corresponding ligand1a.


1964 ◽  
Vol 47 (2) ◽  
pp. 200-208 ◽  
Author(s):  
Fred A. Kind ◽  
Manuel Maqueo ◽  
A. Folch Pi

ABSTRACT Groups of five day old rats were injected with 120 or 240 μg of oestradiol benzoate. When examined at the age of fifty days, the animal presented atrophied testes and marked decreases in the weights of ventral prostate, seminal vesicles and levator ani muscle. Treatment with pregnant mare's serum or with testosterone propionate given from day 20 through day 50 fully restored the gonadal activity. The dose of PMS needed to restore spermatogenesis was 10 IU which was given every third day. Testosterone propionate, 1 mg, given daily was equally effective.


1976 ◽  
Vol 160 (1) ◽  
pp. 43-48 ◽  
Author(s):  
S J Higgins ◽  
J M Burchell ◽  
W I Mainwaring

Tissue wet weight, nucleic acid content and epithelial and stromal cell numbers were measured in the seminal vesicles of sexually mature male rats. After castration, tissue weight and RNA decreased rapidly and in aprallel to reach, after 14 days, values only 15-20% of those in control (not castrated) animals. During this period, DNA decreased to a much lesser extent (by about 40%), but this change in DNA correlates well with the observed loss of cells from the epithelium. Testosterone in vivo promoted an immediate resynthesis of RNA, the value characteristic of control animals being reached within 80h. Delays occurred in the hormone-induced regain of tissue weight (30h) and DNA (40h), each of which preceded proliferation of the epithelium (40-50h). The cells of the stroma were unaffected by these changes in the androgenic statls of the animal. It is suggested that these proliferative changes in the epithelium cannot account for the previously reported induction by testosterone of basic secretory proteins in this tissue.


2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
D. Shanker ◽  
A. K. Rai ◽  
Y. P. Singh ◽  
H. Rehwani ◽  
V. Khushalani ◽  
...  

BenzothiazolineHNC6H4SC︹(C6H5)CH:C(OH)COOCH3 1prepared by the condensation reaction of aroyl pyruvate and 2-aminothiophenol has been treated withPh3Sb(OPri)2to yieldPh3Sb[SC6H4NC(C6H5)CH:CO︹COOCH3] 2. These compounds have been characterized by elemental analyses and molecular weight determinations. The probable structures of the ligand as well as antimony complex have been tentatively proposed on the basis of IR and NMR (H1andC13) spectral evidences. Both compounds have been tested for their antifertility activity in male albino rats. The oral administration of compounds1and2at the dose level of 10 mg/rat/day significantly reduced the weights of testes, epididymides, ventral prostate, and seminal vesicles. The production of preleptotene spermatocytes was decreased by36.57%;57.23%, pachytene spermatocytes by40.06%;62.01%, and secondary spermatocytes by52.45%;63.22%, following the treatment of compounds1and2, respectively. The marked reduction in sperm motility and density resulted in infertility by100%. Significant (P<.01) alterations were found in biochemical parameters of reproductive organs in treated animals as compared to control group. It is concluded that all these effects may finally impair the fertility of male rats.


1971 ◽  
Vol 68 (3) ◽  
pp. 485-501 ◽  
Author(s):  
Lars-Eric Tisell

ABSTRACT The growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated adrenalectomized male rats following daily injections for sixteen days of oestradiol benzoate or cortisone acetate alone, or in combination. Oestradiol was given in daily doses of 0.001 mg or 0.010 mg. Cortisone was administered in daily doses of 1 mg or 3 mg. After oestradiol alone the histological examination revealed an increase in the amount of fibromuscular tissue especially in the coagulating glands and the seminal vesicles but no signs of secretory activity in the epithelium. Cortisone alone induced a moderate stimulation of the epithelium in all the accessory reproductive organs but no signs of secretory activity were observed in the ventral prostate. Oestradiol and cortisone given in combination induced pronounced proliferation of the epithelium in all the accessory reproductive organs. After this treatment the epithelium of the ventral prostate also showed signs of secretory activity. The response of the epithelium in all the accessory reproductive organs was dependent on the size of the dose of both oestradiol and cortisone. Cortisone counteracted the fibromuscular overgrowth especially observed in the coagulating glands and the seminal vesicles after oestradiol given alone. The individual smooth muscle cells, however, were better developed after the combined treatment. The effects of the combined treatment are discussed in the light of the present knowledge of the individual effects of oestradiol and cortisone on the accessory reproductive organs. The importance of including a histological examination in experiments on hormonal dependent growth of the accessory reproductive organs of male rats is emphasized.


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