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The Journal of Experimental Medicine, Vol 72, 747-762, Copyright, 1940, by The Rockefeller Institute for Medical Research New York


ARTICLE

QUANTITATIVE STUDIES OF PROSTATIC SECRETION : II. THE EFFECT OF CASTRATION AND OF ESTROGEN INJECTION ON THE NORMAL AND ON THE HYPERPLASTIC PROSTATE GLANDS OF DOGS



Charles Huggins M.D.1 and Philip Johnson Clark M.D.1

1 From the Department of Surgery of the University of Chicago, Chicago

Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts.

Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state.

In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios.

In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to depression of male hormone production.

Overdosage of estrogen causes the prostate gland of dogs to enlarge, and structures of the posterior lobe and utriculus respond first and most markedly with metaplasia caused by this material. The prostatic enlargement does not resemble the common cystic hyperplasia of senile dogs. Metaplasia rapidly disappears from the prostate, and the epithelial structures quickly return to normal when estrogen is discontinued and androgen is administered.

Submitted on August 15, 1940


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