Anti-androgens do not alter androgen-dependent characteristics of acid phosphatase in the rat ventral prostate

Tenniswood, Martin; Abrahams, Pamela P.; Bird, C. E.; Clark, A. F.

doi:10.1016/0303-7207(84)90047-9

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…We have recently demonstrated that antiandrogen therapy does not inhibit all of the androgen-dependent functions of the rat prostate [7]. There are also reports in the literature that suggest that antiandrogens do not effectively control the androgendependent spread of prostatic carcinoma [29,30].…”

Section: Discussionmentioning

confidence: 67%

“…Even though these marker proteins are androgendependent, antiandrogens such as flutamide and cyproterone acetate do not suppress the secretory acid phosphatase activity [7]. While this inability of antiandrogens to mimic the effects of castration may not extend to all androgen-dependent processes [ S ] , it is important in the light of some of the current treatments for prostatic cancer.…”

Section: Introductionmentioning

confidence: 99%

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Androgen‐repressed messages in the rat ventral prostate

1986

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Poly (A)+ RNA from the prostates of both intact and castrated rats was translated in a message-dependent reticulocyte lysate, and the translation products were electrophoresed on SDS/polyacrylamide gels. Fluorography of these gels showed the expected disappearance, after castration, of the prostate steroid-binding proteins as well as a number of other androgen-dependent proteins. Two major (Mr 40,000 and 45,000) and several minor proteins appeared in the translation products of the castrated rat prostate RNA. Criss-cross liquid hybridization analysis between prostate poly (A+) RNA from intact and castrated rats also showed the disappearance of the abundant prostate steroid-binding protein sequences after castration and the synthesis of several new low to medium abundance sequences. Northern hybridization experiments demonstrated the presence of at least two, and possibly four androgen-repressed poly (A)+ RNA sequences. The most prominent of these, an RNA of 2,000 nucleotides, appeared within 2 days of castration, reaching a maximum on day 4 at a level approximately 400 times greater than the normal level. The other major sequence (a sequence of 1,000 nucleotides) appears after 4 days, reaching a peak between days 8 and 11. Sequences similar to these new RNAs could play an important role in the long-term resistance of prostatic cancer to hormone therapy in humans.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Androgen‐repressed messages in the rat ventral prostate

1986

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“…Both cyproterone acetate (10 mg/day) and flutamide (15 mg/day) reduced OW/BW ratios to 0.5 0.05, respectively, when administered to castrated rats supplemented with 250 pg 5a-DHT/day.The OW/BW ratios of the cyproterone acetate-and flutamide-treated animals decreased to the castrate control levels after 20 days of treatment (results not shown). The doses of cyproterone acetate and flutamide used in these experiments have previously been shown to induce substantial regression in the rat ventral prostate in a manner similar to castration [ 18,. There is a concomitant reduction in the amount of total RNA per prostate 0.2 and 0.3…”

Section: Effect Of Antiandrogens On Organ Weight/body Weight Ratios Amentioning

confidence: 73%

“…The effectiveness of the antiandrogens has usually been monitored by following the decrease or elimination of androgen-dependent functions in the prostate, such as secretory acid phosphatase (SAP), and prostatic steroid-binding protein (PSBP) [58,59]. In the case of cyproterone acetate and flutamide, it has already been demonstrated that antiandrogen therapy does not affect SAP [18], possibly because of the inability of the antiandrogens to totally eliminate the nuclear accumulation of 5a-DHT [60]. The results reported here demonstrate that neither flutamide nor cyproterone acetate is able to fully eliminate C3-PSBP mRNA, presumably for the same reason.…”

Section: Discussionmentioning

confidence: 99%

Treatment with antiandrogens induces an androgen‐repressed gene in the rat ventral prostate

1988

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We have recently described an androgen-repressed gene in the rat ventral prostate, termed TRPM-2, that appears to be involved in the processes of cell regression and programmed cell death. We have analyzed the effect of two antiandrogens currently used in the treatment of prostatic carcinoma on the induction of this gene. Cyproterone acetate (10 mg/day) and flutamide (15 mg/day), when administered to castrated rats receiving a maintenance dose of 5 alpha-dihydrotestosterone proprionate (250 micrograms/day), induce the expression of TRPM-2. Northern hybridization and dot blot analysis demonstrate that TRPM-2 steady-state levels reach a maximum on day 4 of treatment with cyproterone acetate (520 ppm) and on day 6 of treatment with flutamide (190 ppm). During this time the steady-state levels of the androgen-dependent prostate steroid-binding protein mRNA are reduced dramatically (from approximately 75,000 to 10,000 ppm), but are not eliminated even after extended treatment. Treatment with the two antiandrogens produces a substantial reduction in the organ weight/body weight ratio and RNA content of the prostate when compared to rats receiving the maintenance dose alone. These results suggest that while neither cyproterone acetate nor flutamide fully repress the androgen-dependent functions of the prostate, they do induce some of the androgen-repressed sequences in the prostate that have been implicated in the process of cell death.

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“…Androgen-induced changes in citrate levels have not correlated well with morphological changes [26]. We previously reported that quantitation of acid phosphatase activity can provide a more specific marker of androgenicity than incorporation of ['HI-thymidine, but the prostate contains a number of isoenzymes of acid phosphatase and only some of them are stimulated by androgen [6,27]. Moreover, we observed considerable inter-experiment variability in the sensitivity of this parameter.…”

Section: Discussionmentioning

confidence: 84%

Prostatein C₃‐mRNA: A sensitive marker of androgen‐responsiveness in prostate explant cultures

et al. 1990

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Prostatein is an androgen-dependent protein which is secreted by the rat ventral prostate. To determine if prostatein or its mRNA were responsive to androgen in vitro, prostate explants were cultured in media containing 0 or 25 nM dihydrotestosterone (DHT), estradiol (E2), or cortisol (F). Prostatein concentrations in medium were measured by radioimmunoassay at 2 and 4 days and in homogenates at 4 days. They were not changed significantly by any of these steroids. The concentration of the mRNA for the C3-subunit of prostatein was determined by dot hybridization at 0, 2, 4, 6, and 8 days. It was decreased significantly by 2 days when compared with explants cultured in the presence of DHT and significant differences persisted through 8 days. In conclusion, quantitation of the mRNA for the C3-subunit of prostatein in short-term cultures of ventral prostate explants appears to be more sensitive to changes in androgen concentration than does measurement of prostatein, per se. Prostatein C3-mRNA may be a useful marker for in vitro studies of androgen agonists and antagonists.

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Anti-androgens do not alter androgen-dependent characteristics of acid phosphatase in the rat ventral prostate

Cited by 8 publications

References 26 publications

Androgen‐repressed messages in the rat ventral prostate

Androgen‐repressed messages in the rat ventral prostate

Treatment with antiandrogens induces an androgen‐repressed gene in the rat ventral prostate

Prostatein C₃‐mRNA: A sensitive marker of androgen‐responsiveness in prostate explant cultures

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Anti-androgens do not alter androgen-dependent characteristics of acid phosphatase in the rat ventral prostate

Cited by 8 publications

References 26 publications

Androgen‐repressed messages in the rat ventral prostate

Androgen‐repressed messages in the rat ventral prostate

Treatment with antiandrogens induces an androgen‐repressed gene in the rat ventral prostate

Prostatein C3‐mRNA: A sensitive marker of androgen‐responsiveness in prostate explant cultures

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Prostatein C₃‐mRNA: A sensitive marker of androgen‐responsiveness in prostate explant cultures