5α-Reductase as a Target Enzyme for Anti-Prostatic Drugs in Organ Culture

Kadohama, N.; Kirdani, Rashad Y.; Murphy, G.P.; Sandberg, Avery A.

doi:10.1159/000225204

Cited by 15 publications

(4 citation statements)

References 19 publications

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“…Organ culture of prostatic tissue was performed as described previously (Kadohama et al 1977). Explants (2 mm3) prepared from ventral and dorsolateral lobes of prostates were maintained in culture for 7 days in me¬ dium 199 containing varying concentrations of T (0-1.0 pM) and Oe2 (0-0.1 pM).…”

Section: B) In Vitro Experimentsmentioning

confidence: 99%

“…This is in agreement with a previous report on the influence of Oe2 treatment on 5a-reductase activity (Fencle & Villee 1973;Yamanaka et al 1975). Oe2 is a known strong inhibitor of 5ct-reduction of T in vitro (Lee et al 1973;Kadohama et al 1977), butin the castrated animal this type of inhibition may not be of importance. In contrast to the findings of Leav et al (1971) that Oe2 administration to dogs leads to a shift from reductive to oxidative meta¬ bolism of T, we observed some inhibition of I7ß-hydroxy oxidation of T in Oe2-treated rats.…”

Section: )mentioning

confidence: 99%

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A model for studies on the response of the ventral prostate to oestrogens

Corrales

Høisæter

Kadohama

et al. 1981

Acta Endocrinologica

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The effects of oestrogen administration on the weight of ventral and dorsolateral prostates were studied in castrated rats of Wistar-Furth and Copenhagen strains. Direct effect of oestradiol (Oe2) on prostatic tissue was also investigated in organ culture. Oe2\x=req-\ treated animals received daily injections of 50 \g=m\g for 7 days. Control animals were treated with the vehicle only (peanut oil). In 4 month old Copenhagen rats the mean weight of the ventral prostates (42.4 \ m=+-\ 9.4 mg/100 g body weight) was significantly higher than that in the control animals (19.9 \m=+-\4.6 mg/100 g body weight, P < 0.0001). No such differences were observed in older Copenhagen rats (9 months old) or Wistar-Furth rats (3 and 6 months old). Thus, this effect of Oe2 on ventral prostate seems both strain specific and age specific. Similar strain and age differences in the Oe2 effect were found in the dorsolateral prostate, but to a smaller extent. Direct interaction of Oe2 with target tissue was demonstrated in culture as evidenced by the ability of the steroid to prevent regression in explants derived from prostates of Copenhagen rats. The in vivo effects of Oe2 on the prostate weights could not be explained by differences in specific androgen or oestrogen receptor contents or in testosterone (T) metabolism. However, the prostates of younger Copenhagen rats differed from those of all other groups in three respects: 1) they contained high levels of oestramustine binding protein (OeBP), 2) they had the highest amount of uptake of radioactivity into the nuclear residue, and 3) their histological picture was characterized by diffuse stromal architecture having the appearance of oedematous tissue.

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Section: B) In Vitro Experimentsmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

A model for studies on the response of the ventral prostate to oestrogens

Corrales

Høisæter

Kadohama

et al. 1981

Acta Endocrinologica

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“…For more than a decade, the writing has been on the wall that human prostate cancer depends on DHT and not T for hormonal support (see, eg, Kadohama et al [49]). Unfortunately, this hypothesis could not be verified experimentally, as methods for eliminating or lowering DHT levels within the prostate were not available.…”

Section: The Dht Hypothesis Of Prostate Cancermentioning

confidence: 99%

The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications

Petrow

1986

The Prostate

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Data are presented showing that human prostatic adenocarcinoma depends on dihydrotestosterone (DHT) and not testosterone (T) for growth. It follows that androgen ablative therapy should be directed toward elimination of DHT with retention of circulating T. This can be achieved by using a 5 alpha-reductase inhibitor such as 6-methyleneprogesterone (6-MP) (VII). Arguments are presented showing that 6-MP (VII) is expected 1) to function as a prophylactic agent against prostate cancer, 2) to represent an attractive therapeutic modality for palliative treatment of the hormone-responsive disease, and 3) to be compatible with other therapeutic modalities when very low prostatic levels of DHT should be within reach.

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“…Apart from culture media and methodology, the design of an organ culture experiment is also multifaceted and, as yet, there is not a standardized procedure. In particular, the time of testosterone addition is variable as some investigators delay the introduction of testosterone for 24 hours to deplete the explants of endogenous androgens [26,27], while others only add testosterone on the first day of the culture [ 131. Yet Lasnitzki [ 11 concluded that testosterone should be renewed every second day to maintain effective hormone levels.…”

Section: Testosterone Concentrations Ranging From Lo-' Tomentioning

confidence: 99%

Proliferative responses of rat ventral prostate: Effects of variations in organ culture media and methodology

Buchanan¹,

Riches²

1986

The Prostate

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Effects of variations in organ culture media and methodology on the proliferative activity of rat ventral prostate and its response to testosterone were investigated quantitatively by using the incorporation of [125I]-iododeoxyuridine (125I-UdR) to monitor DNA synthesis. In serum-free medium, maximal increases in DNA synthesis occurred when testosterone was introduced during the first 48 hours of the culture. Supplementation of the medium with 5% fetal calf serum did not alter the responses in control or testosterone-treated cultures, whereas the addition of insulin (3 micrograms/ml) alone or in combination with serum promoted cell proliferation in testosterone-free cultures and enhanced the stimulatory effect of testosterone. Unlike grid-supported cultures, suspension cultures of rat ventral prostate exhibited increased proliferative activity both in the presence and absence of testosterone. Thus, variations in experimental procedure may account for differences in the proliferative activity of rat prostate between organ culture studies.

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5α-Reductase as a Target Enzyme for Anti-Prostatic Drugs in Organ Culture

Cited by 15 publications

References 19 publications

A model for studies on the response of the ventral prostate to oestrogens

A model for studies on the response of the ventral prostate to oestrogens

The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications

Proliferative responses of rat ventral prostate: Effects of variations in organ culture media and methodology

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