The complex role of telocytes in female prostate tumorigenesis in a rodent model.

The prostate is not an organ exclusive to the male. It is also found in females of several species, including humans, in which part of the Skene gland is homologous to the male prostate. Evidence is accumulating that changes in the stroma are central to tumorigenesis. Equally, telocytes, a recently discovered type of interstitial cell, are essential for the maintenance of stromal organization. However, it is still uncertain whether there are telocytes in the female prostate and if they play a role in tumorigenesis. The present study used ultrastructural and immunofluorescence techniques to investigate the presence of telocytes in the prostate of Mongolian gerbil females, a rodent model that often has a functional prostate in females, as well as to assess the impact of a combination of N-ethyl-N-nitrosourea, testosterone, and estradiol on telocytes. The results point to the presence of telocytes in the female prostate in the perialveolar and interalveolar regions, and reveal that these cells are absent in regions of benign and premalignant lesions in the gland, in which the perialveolar smooth muscle is altered. Additionally, telocytes are also closely associated with infiltrated immune cells in the stroma. Our data suggest that telocytes are important for both the maintenance of smooth muscle and prostatic epithelium integrity, which indicates a protective role against the advancement of tumorigenesis. But telocytes are also associated with immune cells and a proinflammatory/proangiogenic role for these cells cannot be ruled out, implying that telocytes have a complex role in prostatic tumorigenesis in females.

Postnatal exposure to finasteride causes different effects on the prostate of male and female gerbils.

The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α-reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 µg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three-dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.

Low-dose in utero exposure to finasteride promotes developmental changes in both male and female gerbil prostates.

The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.