Inhibitory effects of estrogens on the testosterone-dependent process of sex accessory fructose secretion.

The simultaneous injections (sc) of testosterone (50 or 400 »g /mouse /day X10) and various estrogens (estradiol benzoate, ethynyl estradiol or diethylstilbestrol) generally resulted in a lowering of both seminal vesicle and anterior prostate fructose levels. Low dose schedules (25 ng daily X10) of estradiol benzoate, ethynyl estradiol, estrone or estriol in the presence of testosterone (50 Mg daily X10) exhibited similar antagonistic activities on fructose levels of mouse sex accessory organs. Intermediate or higher dose schedules (100 or 200 ng daily X10) of ethynyl estradiol plus testosterone (50 ng series) were more effective in reducing fructose levels than were comparable amounts of estradiol benzoate, estriol or estrone. Estradiol benzoate (25 Mg) plus testosterone (400 Mg series) was more effective in lowering fructose than was ethynyl estradiol, estrone or estriol. In the 400 ng testosterone series, intermediate or higher dosages (100 and 200 fig, respectively) of estrogens revealed ethynyl estradiol > estradiol benzoate > estradiol > estrone in antagonizing sex accessory fructose levels in the castrate mouse. Diethylstilbestrol (5,10, 25, 50 or 100 Mg daily X10) caused a lowering of fructose levels in testosterone-treated (50 or 400 ng series) castrate mice. (Endocrinology 78:1084,1966) A NUMBER of earlier investigations have -£*concerned themselves with the effects of injected estrogens on the prostate gland in a variety of species. The action of estrogens on sex accessory organs of castrated laboratory animals treated with testosterone has been briefly reviewed by Huggins and Clark (1). Most earlier investigations have utilized reduced gravimetric responses in male sex hormone target organs as an index for studying androgen-estrogen antagonism. Other studies have examined the histologic alterations produced by the combined administration of these hormones. Although fructose formation by sex accessory organs is known to be andro gendependent (2), few studies have used this "chemical indicator test" to study the interaction of injected amounts of estrogens and Received October 25,1965. This investigation was supported in part by Research Grant RO1 AM 09011-02 MET from the NIH. testosterone. Furthermore, the available information in this regard is not without conflicting results. Simultaneous implants of testosterone and diethylstilbestrol in the castrate rabbit result in a diminution of fructose levels in sex accessory glands (3). Small doses of estradiol in combination with testosterone may actually enhance the stimulatory actions of testosterone and lead to increased amounts of seminal plasma fructose in castrate bulls (4). Deoxycorticosterone, but not estrone, augments fructose contents in the dorsolateral lobes of the prostate of the castrate rat injected with testosterone (5). Recently, it has been shown that the simultaneous implantation of testosterone and estradiol in castrate rats causes increases in fructose contents of the lateral lobes of the prostate. This synergistic effect of the combined hormones is not evident in the dorsal or the anterior lobes of this organ (6). These studies were undertaken to study the interaction of simultaneously injected testosterone and a number of estrogens. Steroid and May 1966 NOTES AND COMMENTS 1085 nonsteroid estrogens were investigated for their ability to influence the androgen-dependent process of fructose formation in sex accessory organs of the castrate mouse. Materials and Methods Castrate mature male albino mice averaging 35.7 g maintained on an ad lib. diet of pellet laboratory chow and water were used in these investigations. Steroids were suspended in peanut oil and administered subcutaneously in a volume of 0.2 ml or less. Simultaneous injections of testosterone and estrogen were initiated 7 days post castration and were continued daily for a period of 10 days. Control groups received daily injections of testosterone (50 or 400 Mg), while experimental groups received both testosterone and estrogen (estradiol benzoate, estriol, estrone, ethynyl estradiol or diethylstilbestrol). All agents were obtained commercially (General Biochemicals, Chagrin Falls, Ohio). Estradiol benzoate, estriol and estrone were injected in dosages of 25, 50, 100 or 200 ng daily X10. Ethynyl estradiol was administered in amounts of 25, 50, 100, 200, 400 or 800 Mg daily X10. Diethylstilbestrol was injected in dosages of 5, 10, 25, 50 or