ANTIANDROGENIC EFFECTS OF THE PINEAL GLAND AND MELATONIN IN CASTRATED AND INTACT PREPUBERTAL MALE RATS

1978 ◽  
Vol 79 (1) ◽  
pp. 77-83 ◽  
Author(s):  
R. ALONSO ◽  
L. PRIETO ◽  
C. HERNANDEZ ◽  
M. MAS

In castrated prepubertal rats, pinealectomy enhanced the testosterone-induced growth response of the seminal vesicles and melatonin inhibited this effect in a dose-related manner. In entire animals, the serum concentration of LH was increased after pinealectomy with no significant changes in other parameters. Administration of melatonin to intact, pinealectomized rats did not affect the serum concentrations of LH or testosterone but caused a doserelated decrease in the weight of the seminal vesicles. The highest dose of melatonin tested reduced the weight of the ventral prostate gland and the uptake of radioactivity by both the ventral prostate gland and the testes after injection of [5-3H]uridine. It is suggested that the pineal gland and melatonin may exert an antagonistic effect on the biological activity of androgens administered to castrated rats and that melatonin can reduce the growth of the accessory sex organs of intact, pinealectomized rats, in spite of a high concentration of LH in the serum. The well-known inhibitory influence of systemically administered melatonin on the accessory sex organs in male rats may be due to its antagonistic effect at a peripheral level.

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


1979 ◽  
Vol 81 (2) ◽  
pp. 209-220 ◽  
Author(s):  
LIDIA WEI LIU KAO ◽  
JUDITH WEISZ

An inhibitor of 5α-reductase, the 17β-carboxylic acid derivative of testosterone (testosterone-17βCA), has been used to evaluate the importance of the 5α-reduction of testosterone in its action on the suppression of LH secretion in male rats. The potential of testosterone-17βCA to inhibit the formation of 5α-dihydrotestosterone (DHT) was first demonstrated in vitro. When homogenates of hypothalami or anterior pituitary glands were incubated with [3H]testosterone in the presence of a 50-fold excess of testosterone-17βCA, the formation of labelled DHT was inhibited by more than 80%. Adult male rats that had been castrated for 1–2 months were fitted with chronic intravenous catheters and implanted with silicone elastomer sheets: one group received one sheet, 0·5–2·0 cm2 in size containing 1·6% testosterone, a second group received one 50 cm2 sheet containing 1·6% testosterone-17βCA and a third group received two sheets, one sheet 50 cm2 in size containing 1·6% testosterone-17βCA and the second ranging in size from 0·5 to 2·0 cm2 and containing 1·6% testosterone. Blood was withdrawn daily from each rat over a 4–5 day period after implantation of the steroids and the level of LH in the plasma was measured by radioimmunoassay. The seminal vesicles and the ventral prostate gland were removed at autopsy on day 4 or 5; the weights of these organs were shown to have increased progressively as the size of the implant of testosterone increased. In contrast, the level of LH in the plasma was suppressed to a comparable extent by implants of testosterone between 0·6 and 2 cm2, whereas a 0·5 cm2 implant of testosterone had no effect. Implants of testosterone-17βCA alone did not influence the weight of the accessory organs or the level of LH. When testosterone-17βCA and testosterone were implanted together, the growth-promoting effect of the latter on the accessory sex organs was significantly reduced. The effectiveness of testosterone in suppressing the level of LH in the plasma of these animals was not influenced by the presence of testosterone-17βCA and in certain instances the level was raised.


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.


1991 ◽  
Vol 3 (3) ◽  
pp. 313 ◽  
Author(s):  
S Sujarit ◽  
RC Jones

The uptake of [3H]thymidine by the epididymis, ventral prostate gland and seminal vesicles was determined in vivo for rats aged 15, 20, 25, 30, 35, 45 and 55 days. The pattern of uptake varied considerably between organs and generally was different from patterns of growth measured as mass or ratio of mass of DNA:tissue. The 'initial segment' of the epididymis and caput and corpus epididymidis showed a similar pattern of [3H]thymidine uptake, being greatest in 15-day-old animals and declining thereafter. On Day 15 the cauda epididymidis had a lower uptake than more proximal regions of the epididymis, but it subsequently showed two significant peaks of increased uptake on Days 25-30 and Day 45. The uptake by the seminal vesicles was high on Day 15, fell to low levels on Day 20, increased considerably from Days 20 to 35, then gradually decreased from Day 35 to 55. The uptake by the prostate gland was a little lower than by the seminal vesicles on Days 15 and 20, then reduced to about the same level as non-reproductive tissues.


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.


1979 ◽  
Vol 3 (1) ◽  
pp. 31-35 ◽  
Author(s):  
P. S. Cook ◽  
M. Notelovitz ◽  
P. S. Kalra ◽  
S. P. Kalra

1970 ◽  
Vol 63 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Kjell J. Tveter

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.


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.


1987 ◽  
Vol 113 (3) ◽  
pp. R7-R9 ◽  
Author(s):  
B.J.A. Furr ◽  
B. Valcaccia ◽  
B. Curry ◽  
J.R. Woodburn ◽  
G. Chesterson ◽  
...  

ABSTRACT Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic–pituitary axis, which leads to an increase in LH and testosterone secretion. A new non–steroidal antiandrogen ICI 176,334 ((2RS)4′-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3′-trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200μg/kg) for 7 days to immature castrated rats, ICI 176,334 (10mg/kg) significantly (P<0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25mg/kg for 14 days to adult rats caused a dose–related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen–responsive benign and malignant diseases.


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