In mammals, antiandrogens affect sexual differentiation and development, causing feminization and demasculinization of male offspring dosed in utero during sensitive developmental stages [17,18].
It is generally known that estrogens are synthesized and act on the testis of mammals including humans. The site of estradiol synthesis in the testis switches to Leydig cells during neonatal development, where the aromatase enzyme is present .
The effect on body weight found in this study was in agreement with the result obtained by Bonkhoff and Remberger , who found that flutamide led to reduced weight gain in their experimental animals compared with the control group. The development and activity of the prostate were dependent on stimulation by the testicular hormones. In the absence of the testis, the prostate failed to develop . In our study, early changes in acini were represented by folding of some areas of acini whereas other acini were rudimentary when treated for 2 weeks. Cystic dilatation of acini with a decrease in the epithelial height was observed in acini treated for 4 weeks. Highly dilated and irregular acini with no stroma in between were observed after 6 weeks of treatment and there was an apparent decrease in the cell number with dilated and congested blood vessels because of the separation of the extracellular matrix element.
Some investigators have studied the process of tissue atrophy in the prostates of mice. They found that the height of the epithelium was reduced to one-half after castrations and that the diameter of the glandular acini also increased rapidly . They concluded that the prostatic epithelium was very sensitive to androgen deprivation. Similar results have been obtained by other researchers [22,23].
Another histological finding obtained in this work in subgroup IIb was the increased amount of interacinar fibromuscular tissue; actually, this increase might have been because of the atrophy of the prostatic acini. This reaction of the interacinar tissue was explained by other researcher in which the stromal remodeling following androgen ablation is also variable [3,24]. They observed that the thickness of the interacinar was almost doubled during castration. The same finding was also obtained by Horn and colleagues [25,26].
A weak PAS reaction was observed in the basal laminae of the acinar epithelium and the secretory material with an irregular apparent thick basement membrane, especially in the folded area. This weak reaction in the apical parts of the cells probably resulted from the decreased supranuclear secretory granules, secondary to the antiandrogenic action of flutamide. A similar result was obtained by Ekman , who found that castration resulted in loss of cell polarity accompanied by alterations in all cell organoids. It has been suggested previously that changes in the composition of the basement membrane and other components of connective tissue markedly influence cell proliferation and differentiation in the prostate, and that these alterations may be of fundamental importance in the etiology and progression of pathological processes .
In this study, the prostates of the rats of subgroup IIb and IIc showed the same histological changes as those in subgroup IIa, but the changes in subgroup IIb and IIc were much more exaggerated and much more diffuse in their distribution. The prostatic acini showed cystic changes with a decrease in epithelial height and some acini were in the form of solid cords and rudimentary.
There are no conflicts of interest.
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