Separation of multiple dihydrotestosterone receptors in rat ventral prostate by a novel micromethod of electro-focusing Blocking action of cyproterone acetate and uptake by nuclear chromatin

1974 ◽  
Vol 359 (1) ◽  
pp. 112-129 ◽  
Author(s):  
Masuyuki Katsumata ◽  
Allen S. Goldman
Keyword(s):  
Cyproterone Acetate ◽  
Ventral Prostate ◽  
Nuclear Chromatin ◽  
Rat Ventral Prostate

BINDING OF ANDROGEN TO COMPONENTS OF RAT VENTRAL PROSTATE NUCLEI IN VITRO

1970 ◽  
Vol 63 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Olav Unhjem
Keyword(s):  
Sodium Chloride ◽  
Radioactive Material ◽  
Ventral Prostate ◽  
Major Portion ◽  
Nuclear Chromatin ◽  
Rat Ventral Prostate

ABSTRACT Following incubation of rat ventral prostate slices with [1,2-3H]testosterone in vitro, radioactive material is found to be associated with the nuclei. Sodium chloride extraction of the nuclei removes macromolecules which might at least partially be responsible for this association. These macromolecules are probably components of the nuclear chromatin. Analyses of the radioactive material indicate that the major portion consists of dihydrotestosterone* and to a lesser extent of testosterone. All the radioactive material is linked non-covalently to the nuclear components responsible for the association.

EFFECT OF PROLACTIN, GROWTH HORMONE AND INSULIN ON THE UPTAKE AND BINDING OF DIHYDROTESTOSTERONE TO THE CULTURED RAT VENTRAL PROSTATE

1976 ◽  
Vol 81 (4) ◽  
pp. 854-864 ◽  
Author(s):  
Risto Johansson
Keyword(s):  
Growth Hormone ◽  
Cyproterone Acetate ◽  
Specific Binding ◽  
Ventral Prostate ◽  
Free Form ◽  
Nuclear Fraction ◽  
Total Uptake ◽  
Rat Ventral Prostate ◽  
Cell Components ◽  
Specific Uptake

ABSTRACT The effects of prolactin, growth hormone and insulin on the total uptake and specific binding of tritiated dihydrotestosterone in the cultured rat ventral prostate were examined. In similar conditions prolactin and insulin act synergistically with testosterone on the macromolecule synthesis of the prostate, but have no effect on the conversion of testosterone to dihydrotestosterone. The total uptake of tritiated dihydrotestosterone to the tissues was slightly, but not statistically significantly, increased by prolactin, insulin and growth hormone. The majority of the radioactive dihydrotestosterone in the tissue was in free form or very loosely bound. None of these three hormones altered the binding of tritiated dihydrotestosterone to the cytoplasmic receptors. Non-radioactive dihydrotestosterone, cyproterone and cyproterone acetate in 1000 foid excess strongly decreased the binding of tritiated dihydrotestosterone to the cytoplasmic reseptors and to the nuclei. That part of the binding, which was inhibited by the hormones was considered to represent the specific binding to the receptors. Insulin stimulated both the specific and the unspecific uptake of dihydrotestosterone to the nuclei. Prolactin only stimulated the specific uptake to the nuclei while growth hormone had no effect. Autoradiography of the nuclear fraction indicated a firm binding of tritiated dihydrotestosterone to the nuclei. The radioactivity of the other contaminating cell components in this fraction appeared to be negligible.

scholarly journals Testosterone action in the rat ventral prostate. The effects of diethylstilboestrol and cyproterone acetate on the metabolism of [3H]testosterone and the retention of labelled metabolites by rat ventral prostate in vivo and in vitro

1971 ◽  
Vol 125 (1) ◽  
pp. 81-91 ◽  
Author(s):  
J. E. Belham ◽  
G. E. Neal
Keyword(s):  
Cyproterone Acetate ◽  
Prostatic Carcinoma ◽  
Prostate Gland ◽  
Target Organ ◽  
Ventral Prostate ◽  
Nuclear Retention ◽  
Rat Ventral Prostate ◽  
Androgenic Effect

Recent reports have indicated that the prior metabolism of testosterone by the secondary sexual tissues may be necessary for its androgenic effect. The effects of two anti-androgens, diethylstilboestrol and cyproterone acetate (17α-acetoxy-6-chloro-1,2α-methylenepregna-4,6-diene-3,20-dione) used in the chemotherapy of human prostatic carcinoma, have been examined on both the metabolism of testosterone and the retention of its metabolites by the rat ventral prostate gland. Cyproterone acetate was found to inhibit the retention of labelled metabolites of [3H]-testosterone by prostatic nuclei, both in vivo and in vitro. This inhibition appeared to be competitive. In contrast with its effect on nuclear retention of metabolites of testosterone, cyproterone acetate had no significant effect on the metabolism of [3H]testosterone by rat ventral prostate tissue. Diethylstilboestrol similarly had little effect on the metabolism of [3H]testosterone by prostatic tissue, although it did appear partially to inhibit its initial metabolism in all the incubation systems used. Diethylstilboestrol inhibited the nuclear retention of dihydrotestosterone when both [3H]testosterone and diethylstilboestrol were injected intraperitoneally in vivo, but had no effect on dihydrotestosterone retention when both testosterone and diethylstilboestrol were supplied directly to the prostate either in vivo or in vitro. It was concluded that if diethylstilboestrol has an anti-androgenic effect at the level of the target organ as distinct from its effect on androgen production by the testes, then it is probably due to a mechanism differing from that of cyproterone acetate.

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.

Alterations in polyamines and nucleic acids in the rat ventral prostate during cyproterone acetate treatment and subsequent withdrawal

1978 ◽  
Vol 56 (5) ◽  
pp. 785-791 ◽  
Author(s):  
B. K. Tsang ◽  
R. L. Singhal
Keyword(s):  
Nucleic Acid ◽  
Cyproterone Acetate ◽  
Prostate Gland ◽  
Total Content ◽  
Ventral Prostate ◽  
Adult Rats ◽  
Rat Ventral Prostate ◽  
Treatment Changes ◽  
Rna:Dna Ratio ◽  
Subsequent Withdrawal

The effect of cyproterone acetate (CA) was examined on polyamines and nucleic acid levels of the ventral prostate at various time intervals after daily administration of this antiandrogen (1.25 mg/100 g, sc) to adult rats. While CA markedly reduced prostatic spermine, spermidine, and putrescine levels after 10 days of treatment, changes in the latter two polyamines appeared to be biphasic with significant elevations being observed at day 1, followed by marked decreases that were evident as early as the 3rd day. Cessation of antiandrogen treatment for 10 days in rats that had been pretreated with CA significantly elevated prostatic spermine levels, while the concentration of spermidine and putrescine remained slightly lower than controls. In contrast, CA failed to exert any marked effect on prostatic spermine and putrescine levels when animals were treated concomitantly with testosterone (5 mg/100 g per day, sc; 10 days). Like prostatic spermidine and putrescine, RNA levels and the RNA:DNA ratio were significantly elevated 24 h after CA administration, but decreased thereafter to levels markedly lower than controls by the 10th day of treatment. DNA concentration was increased slightly during CA administration, although the total content of this nucleic acid remained unaltered. While cessation of CA administration restored RNA and the RNA:DNA ratio to control values, these were significantly increased in rats given both CA and testosterone. Results of the present investigation support the hypothesis that changes in cellular polyamines may be related to alterations in RNA metabolism, and thus cellular differentiation of the prostate gland following androgenic deprivation and (or) depletion.

scholarly journals Intracellular inactivation, reactivation and dynamic status of prostate androgen receptors

1982 ◽  
Vol 208 (2) ◽  
pp. 383-392 ◽  
Author(s):  
Gian Paolo Rossini ◽  
Shutsung Liao
Keyword(s):  
Protein Synthesis ◽  
Androgen Receptor ◽  
Half Life ◽  
Ventral Prostate ◽  
Receptor Complex ◽  
Nuclear Chromatin ◽  
Cytosol Fraction ◽  
Receptor Complexes ◽  
Rat Ventral Prostate ◽  
Energy Dependent

The dynamic status of the androgen receptor in prostate cells was studied by incubation of rat ventral prostate with radioactive 17β-hydroxy-5α-androstan-3-one (5α-dihydrotestosterone) in the presence and absence of respiratory poisons and inhibitors of protein and RNA synthesis and also by isotope chasing of the radioactive androgen–receptor complexes. The androgen receptor in the prostate appears to go through a dynamic process of recycling between the cytoplasm and the nucleus as well as an inactivation process. The radioactive androgen–receptor complex, however, is maintained at a constant level for at least 2h during incubation at 37°C, even in the absence of new protein synthesis, suggesting that early androgen actions may not require a depletion of a major portion of cellular receptor. In the presence of 2,4-dinitrophenol, the androgen receptor is rapidly deactivated (half life, 2min). The inactive receptor can be reactivated efficiently by an energy-dependent process, even in the absence of protein synthesis. Receptor binding of androgen and nuclear chromatin binding of the androgen–receptor complex are fast processes; half-maximum binding can be achieved within 1 and 10min respectively. On the contrary, the overall process of the release of the receptor complex from nuclear chromatin and its reappearance in the cytosol fraction has a long half life of about 70min. This slow process may reflect the involvement of the steroid–receptor complex in a time-consuming mechanism that is essential for hormone responses. Actinomycin D can increase the nuclear receptor level by 50% or more. This increase is not due to a decrease in the rate of receptor release from nuclei or to inhibition of DNA degradation by the antibiotic.

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