The EFFECT OF OESTRADIOL-3N-BIS-(2-CHLOROETHYL)CARBAMATE-17β-PHOSPHATE (ESTRACYT®) ON THE 5α-Reductase IN THE RAT VENTRAL PROSTATE

Abstract

The ventral prostate of the rat both after in vitro incubation and in vivo experiments was found to contain appreciable 5\g=a\-reductaseactivity, whilst a very low activity was registered in the diaphragm and liver. Neither Estracyt\s=r\ nor LEO275 (Estracyt\s=r\ without the phosphate group in position 17 of the oestradiol moiety) had an inhibitory effect on the enzyme activity after in vitro incubation but equivalent amounts of oestradiol-17\g=b\ and oestradiol-17\g=b\-phosphatesignificantly reduced 5\ g=a\ \ x=r eq-\ reductase activity. When Estracyt\s=r\ was injected in vivo no influence on activity was registered in "short term" experiments while a significant inhibition was found after "long term" treatment in vivo. Possible explanations for this "long term" effect of Estracyt\s=r\ on 5\g=a\-reductase activity are discussed.

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

“…The dorsolateral lobe of the rat prostate displays unique sensitivity to estrogenic action in other respects not seen in the ventral lobe. Thus, estrogen induced uptake of 65Zn by the rat dorsolateral prostate in a highly tissue-specific manner [15], Zinc is a potent inhibitor of 5a-RA, at least in nuclei of rat ventral prostate [7], Whether this relationship of estrogens, zinc and 5a-reduction is signi ficant to the mechanism of the anti-androgen action of estro gens remains to be determined. Synthetically modified steroids and steroid-cytostatic com plexes are being increasingly utilized in chemotherapy.…”

“…It has been shown that one of the properties in its anti-androgenic action is an influence on 5 a-R A [7,8,19]. In vivo administration of estracyt to dogs and rats resulted in diminished 5a-RA of their prostates [8], H isaeter [7] reported no effect by estracyt on the rat ventral prostate after in vitro incubation or short-term (half-hour) in vivo adminis tration of the drug. Marked inhibitory effect was observed only after long-term (3 days) administration of estracyt.…”

Effects of Tamoxifen on the Binding and Metabolism of Testosterone by Human Prostatic Tissue and Plasma in Vitro

“…Some may suppress the interstitial cell stimulating hormone with consequent reduction in testosterone secretion (Alder, Burger, Davis, Dulmanis, Hudson, Sarfaty & Straffon, 1968;Kirschner & Schneider, 1972). Other workers have also demonstrated a direct influence by these agents on the andro¬ genic activity of the prostate (Farnsworth, 1969;Albin, Vittek, Gordon, Altman, Olivo & Southren, 1973;Jenkins & McCaffery, 1974;Hoisaeter, 1975).…”