Effect of perphenazine on growth and zinc‐65 uptake of the rat prostatic adenocarcinoma, R 3327

Abstract

Prolactin affects the growth and function of both normal and carcinatomous prostate tissue. Therefore, the effect of modifying prolactin secretion on the growth of the adenocarcinoma of the rat prostate (R3327) was studied, utilizing chronic administration of the dopamine antagonist perphenazine. At 4 and 8 weeks after tumor inoculation, perphenazine (0.5 and 1.0 mg per dose) was injected for 12-16 weeks. Tumors weighed at autopsy showed that the 0.5 mg dose resulted in significantly smaller and the 1.0 mg dose, in significantly larger tumors than the controls. Perphenazine at both doses increased serum prolactin, but the increase was greater when 0.5 mg was administered. There was a higher uptake of 65Zn when the tumor growth was inhibited as in the animal receiving 0.5 mg of perphenazine. Several possible explanations are offered for the results, including the fact that prolactin might follow a bell-shaped curve in its effect on the tumor and that perphenazine might have other mechanisms of action besides dopamine antagonism.

LY207320 (6‐methylene‐4‐pregnene‐3,20‐dione) inhibits testosterone biosynthesis, androgen uptake, 5α‐reductase, and produces prostatic regression in male rats

“…PRL appears to regulate the proliferation and function of prostatic cells in a biphasic fashion. In the rat, low to intermediate PRL levels augment the agonistic actions of T, while high PRL levels inhibit normal [32] and neoplastic [33] prostatic growth. LY207320 had no effect on serum PRL levels in reserpinized rats.…”

Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer

“…Consequently, the development of a natural or synthetic recombinant human prolactin preparation or an animal source of prolactin compatible for human use is required. An alternative but less desirable approach would be to enhance the pituitary release of prolactin by agents such as estrogen or perphenazine [45], provided that such agents do not have direct effects on inhibiting zinc uptake by the malignant cells and are not contraindicated by other adverse effects.…”

Letter to the editor

“…Such a mechanism might explain early observations associating hyperprolactinemia or exogeneous PRL administration with impaired growth of transplantable R3327 prostate adenocarcinomas in rats [5,6]. Members of the PRL family may play an integral part in the regulation of angiogenesis.…”