The effect of some stilboestrol compounds on DNA polymerase from human prostatic tissue

Harper, M. E.; Fahmy, A. R.; Pierrepoint, C. G.; Griffiths, K.

doi:10.1016/s0039-128x(70)80006-x

Cited by 25 publications

(9 citation statements)

References 20 publications

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“…and DES have been shown to affect several steps concerned with the regulation of prostatic growth, inhibition of testosterone metabolism (Farnsworth, 1969;Groom et al 1971), nucleic acid synthesis and metabolism (Mangan, Neal & Williams, 1967) and decreased uptake and retention of 5a-dihydrotestosterone by prostatic cell nuclei (Fang & Liao, 1969). The activity of DNA polymerase was shown to be inhibited by stilboestrol and some of its derivatives including DHBS (Fahmy & Griffiths, 1968;Harper et al 1970). DHBS was as effective as DES and oestradiol-17/?…”

Section: Plasma Testosterone and Androstenedionementioning

confidence: 99%

“…and diethylstilboestrol affects testosterone meta¬ bolism by prostatic tissue in vitro (Farnsworth, 1969;Farnsworth, 1970;Groom, Harper, Fahmy, Pierrepoint & Griffiths, 1971). Furthermore, following the report (Fahmy & Griffiths, 1968) that diethylstilboestrol and some of its analogues inhibited the activity in vitro of calf thymus DNA polymerase (DNA nucleotidyl-transferase EC 2.7.7.7), it was shown that these compounds had a similar inhibitory effect on the enzyme in human neoplastic prostatic tissue (Harper, Fahmy, Pierrepoint & Griffiths, 1970). Alkyl substitution in the eux' position of stilboestrol appeared to increase the inhibitory effect on DNA polymerase while both diethylstilboestrol and dihydrodibutylstilboestrol, which contains a saturated '-ethylenic linkage, con¬ sistently inhibited enzymic activity.…”

Section: Introductionmentioning

confidence: 98%

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The Effect of Certain Stilboestrol Analogues on Plasma Prolactin and Testosterone in the Rat

Danutra¹,

Harper²,

Boyns³

et al. 1973

Journal of Endocrinology

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Oestradiol-17\g=b\,diethylstilboestrol (DES), dl-dihydrodibutylstilboestrol (dl-DHBS) and meso-dihydrodibutylstilboestrol (meso-DHBS) were injected intramuscularly into male Sprague-Dawley rats in a daily dose of 100 \ g=m\ g for a period of 10 days. Oestradiol-17\g=b\ and DES decreased the weight of the prostate and seminal vesicles to the same extent, whereas meso\x=req-\ DHBS was less effective. dl-DHBS was almost inactive. Only oestradiol\x=req-\ 17\g=b\ and DES caused a decrease in the weight of the testes. The adrenal glands increased in weight after administration of either oestradiol-17\g=b\, DES or meso-DHBS.Four hormones in the plasma were measured: testosterone, androstenedi\x=req-\ one, prolactin and interstitial cell-stimulating hormone (ICSH). DES decreased the plasma concentration of both ICSH and testosterone. Oestradiol-17\g=b\ and meso-DHBS administration resulted in a lowering of the plasma testosterone concentration with no effect on ICSH. Oestradiol-17\g=b\, DES and meso-DHBS markedly increased plasma prolactin concentrations. dl-DHBS appeared to have little biological effect causing only very small changes in all the parameters investigated.

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Section: Plasma Testosterone and Androstenedionementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

The Effect of Certain Stilboestrol Analogues on Plasma Prolactin and Testosterone in the Rat

Danutra¹,

Harper²,

Boyns³

et al. 1973

Journal of Endocrinology

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“…Evidence also indicates that estrogens directly inhibit testosterone synthesis by the testes [23] and increase the pituitary production of prolactin. In high concentrations, they also inhibit DNA synthesis by the prostatic cells [24].…”

Section: Estrogen Therapymentioning

confidence: 99%

Hormonal Therapy for Advanced Prostatic Carcinoma

1989

J. Surg. Oncol.

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Since the work of Huggins and Hodges, hormonal therapy, i.e., orchiectomy or estrogens, has been the gold standard of treatment for patients with advanced adenocarcinoma of the prostate. Recently, many new drugs have been introduced in the hope of achieving a beneficial response as compared with hormonal therapy, while avoiding some of the adverse effects. Various newer agents are reviewed. It appears that while these agents may be attractive secondary to specific effects, they do not appear to offer any survival advantage over diethylstilbestrol or orchiectomy .Finally, the theory of total androgen blockade is reviewed. Institution of total blockade does not appear to offer a survival advantage over standard androgen blockade.

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“…This can be achieved by castration or by estrogen therapy which, by depressing LH secretion from the pituitary gland, reduces serum androgen almost to castration levels. Reports that estrogen therapy acts directly on the prostate cell (30,34) remains a matter of debate (58).…”

Section: Background For Endocrine Therapymentioning

confidence: 99%

Steroid Receptors in Urological Malignancies

Ekman¹

1981

Acta Obstet Gynecol Scand

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Within urological practice, three important types of cancer seem to be under endocrine influence or develop in endocrine-dependent organs: prostate cancer, hypernephroma and testicular tumors. Endocrine therapy is not used in testicular cancer, its value in renal cell carcinoma is limited, whereas it is a dominant form of therapy for prostate cancer. There seems to be a definite relation between androgen receptor content in primary prostatic carcinoma and response to hormonal manipulations. The presence of estrogen receptors is not well documented and probably the major effect of estrogen therapy is indirect, being exerted via the hypothalamo-pituitary axis. Progestin receptors are present in hyperplastic prostate as well as in prostate cancer and may indicate cases sensitive to progestin therapy. The assay method still needs considerable refinement before it can be introduced into clinical practice.

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The effect of some stilboestrol compounds on DNA polymerase from human prostatic tissue

Cited by 25 publications

References 20 publications

The Effect of Certain Stilboestrol Analogues on Plasma Prolactin and Testosterone in the Rat

The Effect of Certain Stilboestrol Analogues on Plasma Prolactin and Testosterone in the Rat

Hormonal Therapy for Advanced Prostatic Carcinoma

Steroid Receptors in Urological Malignancies

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