Inhibition of prostatic growth in rats by 6-methylene-4-pregnene-3,20-dione

1982 ◽  
Vol 95 (3) ◽  
pp. 311-313 ◽  
Author(s):  
Vladimir Petrow ◽  
G. M. Padilla ◽  
Keith Kendle ◽  
A. Tantawi
Keyword(s):  
Body Weight ◽  
Seminal Vesicles ◽  
Ventral Prostate ◽  
Irreversible Inhibitor ◽  
Immature Rats ◽  
Daily Dose ◽  
Prostatic Growth ◽  
Rat Prostate

6-Methylene-4-pregnene-3,20-dione, a potent irreversible inhibitor of rat prostate 5α-reductase in vitro, markedly inhibited the growth of the ventral prostate and seminal vesicles in immature rats when administered s.c. in a daily dose of 100 mg/kg body weight for 35 days. Kidney and testes weights were reduced, together with some reduction in body weight. In the mature rat treated with this steroid in a dose of 40 mg/kg body weight per day for 11 days, marked regression in ventral prostate and seminal vesicles was observed.

THE BINDING OF [1,2-3H]TESTOSTERONE WITHIN NUCLEI OF THE RAT PROSTATE

1969 ◽  
Vol 44 (3) ◽  
pp. 323-333 ◽  
Author(s):  
W. I. P. MAINWARING
Keyword(s):  
Molecular Weight ◽  
Equilibrium Dialysis ◽  
Prostate Gland ◽  
Ventral Prostate ◽  
Rat Tissues ◽  
Receptor Complex ◽  
Rat Prostate ◽  
Binding Component

SUMMARY The specificity of the binding of [1,2-3H]testosterone to nuclei of various rat tissues in vivo has been studied. A significant amount of radioactivity was retained in the nuclei of androgen-dependent tissues only, particularly the ventral prostate gland. The bound radioactivity was only partially recovered as [1,2-3H]testosterone; the remainder was identified as [3H]5α-dihydrotestosterone. Efforts were made to characterize the binding component, or 'receptor', in prostatic nuclei. On digestion of nuclei labelled in vivo with [1,2-3H]testosterone, with enzymes of narrow substrate specificity, only trypsin released tritium, suggesting that the receptor is a protein. On the basis of subfractionation studies of labelled nuclei, the receptor is an acidic protein. The androgen—receptor complex could be effectively extracted from the prostatic nuclei in 1 m-NaCl and from the results of fractionations on a calibrated agarose column, the complex has a molecular weight 100,000–120,000. The specificity of the binding of steroids to such 1 m-NaCl extracts in vitro was investigated by the equilibrium dialysis procedure. Under these conditions, the specificity of the binding of [1,2-3H]testosterone demonstrated in vivo could not be simulated. The receptor is probably part of the chromatin complex but its precise intranuclear localization cannot be determined by biochemical procedures alone.

scholarly journals Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

2006 ◽  
Vol 50 (6) ◽  
pp. 1989-1992 ◽  
Author(s):  
James E. Moon ◽  
Michael C. Ellis ◽  
Matthew E. Griffith ◽  
Joshua S. Hawley ◽  
Robert G. Rivard ◽  
...  
Keyword(s):  
Body Weight ◽  
Untreated Control ◽  
Antimicrobial Agents ◽  
Leptospira Interrogans ◽  
In Vitro Activity ◽  
Hamster Model ◽  
In Vivo Efficacy ◽  
Daily Dose

ABSTRACT Human studies support the use of β-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Ninety to 100% of doxycycline controls, treated for 5 days with 5 mg/kg of body weight of drug, survived to 21 days. Treatment with azithromycin (daily dose: 6.25, 12.5, 25, 50, 100, or 200 mg/kg) resulted in 100% survival at all evaluated doses. Animals receiving 20 mg/kg or more of clarithromycin (daily dose: 1, 5, 10, 15, 20, 40, 60, or 100 mg/kg) had improved survival. Ninety-eight percent of animals treated with telithromycin (daily dose: 1, 5, 10, 15, 20, or 40 mg/kg) survived. We conclude that all agents tested have demonstrated in vivo efficacy in treating acute leptospirosis. These results provide support for further evaluation of macrolide and ketolide antimicrobial agents in human trials.

SOME EFFECTS OF SIMULTANEOUS ADMINISTRATION OF NORETHANDROLONE AND CORTISONE IN THE RAT

1959 ◽  
Vol XXXII (IV) ◽  
pp. 536-544 ◽  
Author(s):  
J. G. Llaurado ◽  
J. B. Trunnell ◽  
J. L. Claus
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Opposite Effect ◽  
Levator Ani ◽  
Seminal Vesicles ◽  
Ventral Prostate ◽  
Simultaneous Administration ◽  
Concurrent Administration ◽  
Consistent Effect ◽  
Delayed Growth

ABSTRACT An investigation was undertaken in an attempt to determine whether norethandrolone (NEA) antagonizes all or some of the catabolic effects of 17-hydroxycorticoids. Fourteen groups of eight male young rats (intact, gonadectomized, adrenalectomized and adrenalectomized-gonadectomized) were given subcutaneously either the solvent, NEA (1 mg/day), cortisone (1 mg/day) or a combination of both for 21 days. Results show that administration of NEA has a moderate but consistent effect in increasing body weight of rats receiving no other steroid as well as in preventing the delayed growth rate of those receiving cortisone. In both intact and gonadectomized animals, NEA largely prevented the intense atrophy of the adrenals induced by cortisone. An increase in levator ani weight was promoted by NEA regardless of concurrent administration of cortisone. The latter induced a diminution in the size of seminal vesicles, coagulating glands and ventral prostate, whereas NEA had the opposite effect; when given together the effect of NEA was potentiated. Treatment with NEA alone was shown to have a marked thymolytic effect and also to potentiate the thymolytic effect of cortisone when given together. These results suggest that in some tissues NEA antagonizes, and in others augments, some of the catabolic actions of 17-hydroxycorticoids

FORMATION OF 5α-REDUCED PRODUCTS FROM TESTOSTERONE IN VITRO BY GERM CELLS FROM IMMATURE RATS

1972 ◽  
Vol 71 (2) ◽  
pp. 393-408 ◽  
Author(s):  
Morio Yamada ◽  
Shunji Yasue ◽  
Keishi Matsumoto
Keyword(s):  
Germ Cells ◽  
Ventral Prostate ◽  
Seminiferous Tubules ◽  
Immature Rat ◽  
Collagenase Treatment ◽  
Incubation Study ◽  
Reduced Products ◽  
Immature Rats ◽  
Tissue Homogenates

ABSTRACT In the incubation study of [3H] testosterone with tissue homogenates in the presence of NADPH, it was shown that the rate of production of the sum of all 5α-reduced products by 30-day-old rat testes (50 to 100 nmoles/g tissue or 100 mg protein/h) was of the order of twenty times that by the ventral prostate (2 to 4 nmoles/g tissue/h). The activities of the C19-steroid Δ4-5α-reductase of the seminiferous tubules, germ cells and tubular non-germ cells isolated from immature rats (7 to 10, 11 to 13 and 5 to 7 nmoles/100 mg protein/h, respectively) were of similar order to those of the prostate, while much less activity was found in the spleen and muscle. It was also noted that the activity of the 5α-androstane-3α-, and -3β-hydroxysteroid dehydrogenase seemed to be higher in each tissue of immature rat testes than in the prostate tissue. The seminiferous tubules were isolated by collagenase treatment and germ cells were separated from non-germ cells by tubular cell culture at 34°C for 2 days. Thus, germ cells of immature rat testes seem to have the characteristics of androgen responsive tissue.

BIOLOGIC AND BIOCHEMICAL EFFECTS OF ANTI-ANDROGENS ON RAT VENTRAL PROSTATE

1974 ◽  
Vol 75 (2) ◽  
pp. 385-397 ◽  
Author(s):  
Jack Geller ◽  
Kevin McCoy
Keyword(s):  
Complex Formation ◽  
Protein Complex ◽  
Ventral Prostate ◽  
Common Denominator ◽  
Biochemical Effects ◽  
Protein Complex Formation ◽  
Biologic Effects ◽  
Rat Prostate

ABSTRACT To determine whether the similarity of biologic effects of two antiandrogens, cyproterone acetate (Cyp A) and edogesterone (PH-218), could be related to one or more common biochemical effects, we have compared the effects of both drugs on 3H testosterone (3HT) entry into cells, binding to specific cytosol and nuclear androphiles, and conversion to dihydrotestosterone (DHT). In chronic in vivo studies, both Cyp A and PH-218 reduced rat prostate weights by approximately 50% and specific cytosol steroid-protein complex formation by approximately 60 %. At the same time, Cyp A decreased the formation of nuclear steroid-protein complex to 10% of control values, compared with 40% for PH-218. In addition, Cyp A, but not PH-218, significantly decreased total 3HT uptake by the prostate. Similar effects of Cyp A on 3HT uptake, binding, and metabolism were noted in acute in vivo and in vitro experiments. PH-218 effects on these same parameters were reduced in acute, compared to chronic, studies. Neither drug significantly affected the conversion of T to DHT. Despite quantitative differences between Cyp A and PH-218, these studies support the concept that the biochemical common denominator for the biologic effects of anti-androgens is inhibition of specific steroid-protein complex formation in both cytosol and nucleus.

Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats

1987 ◽  
Vol 116 (2) ◽  
pp. 193-199 ◽  
Author(s):  
Santosh K. Varma ◽  
Eric Bloch
Keyword(s):  
Body Weight ◽  
Seminal Vesicle ◽  
Medroxyprogesterone Acetate ◽  
Placental Tissue ◽  
Endocrine Function ◽  
Male Rats ◽  
Ventral Prostate ◽  
Pregnant Rats ◽  
Testosterone Synthesis

Abstract. The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P < 0.01). Foetal body weights (P < 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P < 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. The results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus. The diminished activity of adult testes indicates a permanent effect of in utero mestranol exposure on testes function.

The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor progestagen, on the rat prostate

1987 ◽  
Vol 115 (4) ◽  
pp. 544-550 ◽  
Author(s):  
Jacqueline Botella ◽  
Jacques Paris ◽  
Brahim Lahlou
Keyword(s):  
Androgen Receptor ◽  
Cyproterone Acetate ◽  
Megestrol Acetate ◽  
Ventral Prostate ◽  
Chlormadinone Acetate ◽  
Rat Ventral Prostate ◽  
Nomegestrol Acetate ◽  
Nuclear Location ◽  
Rat Prostate

Abstract. Nomegestrol acetate, like other synthetic progestins such as medroxyprogesterone acetate (MPA), chlormadinone acetate, megestrol acetate and cyproterone acetate, is able to modify the physiological actions of androgens. In the present study, the effects of nomegestrol acetate and other antiandrogens on the binding of androgen to the androgen receptor (AR) and on the 'activation' of this receptor were investigated, using rat ventral prostate as target model. Relative binding affinities (RBA) for AR were first estimated in vitro with respect to [3H]testosterone for a series of structurally-related compounds. The values obtained ranged as follows: dihydrotestosterone (DHT) » megestrol acetate ≥ testosterone (T) > nomegestrol acetate > 19-nor progesterone (19NP) > progesterone (P). An assay was established, using two different incubation times (3 h and 24 h) to further investigate relationships between binding affinity and androgenic, or antiandrogenic, activity. The following order (as %) was obtained for progestins as against [3H]mibolerone (DMNT): 1) DMNT (100) » acetate (42) > megestrol acetate (29) > chlormadinone acetate (9) > MPA (8) > cyproterone acetate (6) after 3 h and 2) DMNT (100) » MPA (53) » nomegestrol acetate (19) > megestrol acetate (12) > chlormadinone acetate (14) and cyproterone acetate (8) after 24 h. Since the RBA of nomegestrol acetate declined with time, these results indicate that this substance may act like an antiandrogen rather than an androgen, while the contrary prevails concerning MPA. The effects of these progestins, administered either alone or in combination with DHT to the animals, on the location (nuclear or cytosolic) of AR were also analyzed. DHT (0.05 or 4 mg/kg) produced maximal nuclear location of AR. Of the progestins tested, only MPA and norethisterone acetate reproduced this effect, while other steroids were ineffective. Furthermore, cyproterone acetate, megestrol acetate and nomegestrol acetate were able to inhibit to a large extent the DHT-elicited effect. The evidence from these studies suggests that the new compound nomegestrol acetate may oppose the actions of androgens on ventral prostate by directly interacting with the androgen receptor.

STUDIES ON THE SUBACUTE AND CHRONIC ADMINISTRATION OF STILBESTROL IN THE MALE RAT

1954 ◽  
Vol 32 (1) ◽  
pp. 41-49 ◽  
Author(s):  
D. W. Snair ◽  
Sybil E. Jaffray ◽  
H. C. Grice ◽  
L. I. Pugsley
Keyword(s):  
Body Weight ◽  
Chronic Administration ◽  
Seminal Vesicles ◽  
Reproductive Capacity ◽  
Male Rat ◽  
Breeding Experiment ◽  
Percentage Decrease ◽  
The Third ◽  
Accessory Sex Organs ◽  
Daily Dose

The temporary effects of the administration of stilbestrol upon body weight, weight of the accessory sex organs, and the reproductive capacity of the male white rat have been studied. A linear relationship was obtained when the logarithm of the dose of stilbestrol administered (0.0125 to 5.0 mgm.) was plotted against the percentage decrease in testes weight. This same relationship was also found when the log of the dose was plotted against the percentage decrease in body weight although this line had a much more gradual slope.When the administration of stilbestrol was discontinued, the seminal vesicles coagulating glands, and ventral prostrates regained their weight by the third to fourth week but the weights of the testes remained below the control values until the sixth to ninth week. In a breeding experiment it was shown that a daily dose of 7.5 μgm. of stilbestrol causes sterility in the male. This does also slightly affected the weight of the accessory sex organs and their cellular structure.

TESTOSTERONE AND THE GROWTH OF MAMMARY GLANDS AND OTHER TISSUES OF HYPOPHYSECTOMIZED RATS TREATED WITH THYROXINE, INSULIN AND CORTISONE

1960 ◽  
Vol XXXIII (II) ◽  
pp. 214-229 ◽  
Author(s):  
B. T. Donovan ◽  
Dora Jacobsohn
Keyword(s):  
Body Weight ◽  
Growth Response ◽  
Adrenal Glands ◽  
Testosterone Propionate ◽  
Ovarian Hormones ◽  
Mammary Glands ◽  
Seminal Vesicles ◽  
The Body ◽  
Ventral Prostate ◽  
Hypophysectomized Rats

ABSTRACT The reaction of the mammary glands to testosterone propionate was studied in gonadectomized, hypophysectomized rats treated with thyroxine, insulin and cortisone in various combinations. The weight and length of the body and the weight of the liver, heart ventricles, adrenal glands, seminal vesicles and ventral prostate was also recorded. Growth of alveolar lobules, such as produced by injections of testosterone into rats with intact pituitary gland did not occur in any of the 3 groups of hypophysectomized rats studied, that is, neither after treatment with testosterone and 1) thyroxine and cortisone, 2) insulin and cortisone, nor 3) thyroxine, insulin and cortisone. An abnormal elongation of side buds and a hyperplasia and proliferation of ductal epithelium did occur and was most prominent in the group receiving insulin and cortisone. A marked increase in body length, as well as in body weight, was observed in the group treated with testosterone, thyroxine, insulin and cortisone. The results are discussed with regard to the enhanced growth response to ovarian hormones observed in this laboratory under similar conditions.

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