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.

MEASUREMENT OF FREE AND OCCUPIED CYTOPLASMIC AND NUCLEAR ANDROGEN RECEPTOR SITES IN RAT VENTRAL PROSTATE GLAND

1977 ◽  
Vol 74 (3) ◽  
pp. 393-404 ◽  
Author(s):  
PETER DAVIES ◽  
PHILIP THOMAS ◽  
KEITH GRIFFITHS
Keyword(s):  
Androgen Receptor ◽  
Specific Binding ◽  
Prostate Gland ◽  
Ventral Prostate ◽  
Reliable Estimate ◽  
Exchange Method ◽  
Receptor Proteins ◽  
Receptor Sites ◽  
Rat Ventral Prostate ◽  
Fold Excess

SUMMARY A method has been developed which allows the estimation of occupied and unoccupied androgen receptor sites in both cytoplasmic and nuclear fractions of rat ventral prostate. The procedure involves precipitation of receptor proteins and incubation of precipitates with labelled 5α-dihydrotestosterone. Uptake of 3H-labelled steroid at 0–4 °C gives an indication of free receptor, whereas binding at a raised temperature (15 °C) allows estimation of occupied receptor. Non-specific binding was measured in the presence of a 100-fold excess of unlabelled 5α-dihydrotestosterone. The exchange method was specific for androgens, and specific binding was detected only in fractions of androgen-dependent tissues. The method can be applied to cytosol, whole nuclei, chromatin and salt-extractable and salt-resistant protein preparations from nuclear fractions, and gives a reliable estimate of total receptor sites when occupied as compared with control measurements of unoccupied sites.

scholarly journals Solubilization of Testosterone 5α-Reductase from Nuclear Fraction of Rat Ventral Prostate

1973 ◽  
Vol 20 (5) ◽  
pp. 489-495 ◽  
Author(s):  
JUN SHIMAZAKI ◽  
YUMIKO OHKI ◽  
HIROSHI KURIHARA ◽  
NOBUO FURUYA ◽  
KEIZO SHIDA
Keyword(s):  
Ventral Prostate ◽  
Nuclear Fraction ◽  
Rat Ventral Prostate

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.

EFFECT OF 17α-METHYL-β-NORTESTOSTERONE (SK & F 7690) ON THE BINDING IN VITRO OF 5α-DIHYDROTESTOSTERONE TO MACROMOLECULAR COMPONENTS FROM THE RAT VENTRAL PROSTATE

1971 ◽  
Vol 66 (2) ◽  
pp. 352-356 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Tissue Culture ◽  
Protein Complex ◽  
Incubation Medium ◽  
Culture Medium ◽  
Tissue Culture Medium ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nuclear Fraction ◽  
Rat Ventral Prostate

ABSTRACT Slices from prostate glands of castrated male rats were incubated with [3H] 5α-dihydrotestosterone in Eagle's tissue culture medium. The labelled androgen was associated with androphilic macromolecules both in the prostatic cytosol and the nuclei. The addition of the anti-androgenic compound, 17α-methyl-β-nortestosterone (SK & F 7690) to the incubation medium inhibited the formation of the nuclear 5α-dihydrotestosterone-protein complex, and markedly reduced the cytosol 5α-dihydrotestosterone-protein complex. Likewise, the uptake of [3H] 5α-dihydrotestosterone by the prostatic nuclear fraction was reduced by about 40%.

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