Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate

Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5alpha-reductase (5alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

Experimental endocrine therapies promote epithelial cytodifferentiation and ciliogenesis in the gerbil female prostate

The incidence of ciliated cells in the prostate gland of the female gerbil (Meriones unguiculatus) is uncommon and apparently becomes more frequent during androgen (testosterone cypionate) and anti-estrogen (letrozole) endocrine therapies. To evaluate the effects of such drug therapies on the induction of ciliogenesis in the glandular epithelium of female prostate glands, adult female gerbils aged 90 days were treated for 14 days with testosterone and letrozole after which their prostate glands were removed for histological, ultrastructural, and serological analyses. The cytodifferentiation of the ciliated phenotype in the alveolar epithelium became more frequent after both the testosterone and the letrozole treatments. The ciliogenesis phenomenon of the epithelial cells in the prostate gland of female gerbils thus appears to be induced by variations in the increase of androgen levels.

Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders

The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.

Exposure to ethinylestradiol during prenatal development and postnatal supplementation with testosterone causes morphophysiological alterations in the prostate of male and female adult gerbils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiestrogen therapies affect tissue homeostasis of the gerbil (Meriones unguiculatus) female prostate and ovaries

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Anatomy of smooth muscle cells in nonmalignant and malignant human prostate tissue

Differently graded areas of human prostate adenocarcinoma were examined after Masson's trichrome staining or immunohistochemistry for smooth muscle alpha-actin, type IV collagen and laminin. In addition, the ultrastructure of the prostatic smooth muscle cells (SMC) during glandular proliferation and epithelial invasion in selected tumors was studied. The SMC formed a thick layer below the epithelial structures in unaffected areas and were closely associated with each other in homotypic interactions. As the tumor grade increased, the SMC gradually lost interactions with each other and became atrophic. With the growth of the epithelial compartment, the SMC initially segregated to the tumor periphery and the intercellular spaces increased. In high grade tumors, the epithelial cancer cells invaded the spaces between the SMC. Immunohistochemical analysis of the basal membrane revealed increased disruption of the usually thick basal membrane, which became thinner and faintly stained with each of the antibodies used. We conclude that most SMC become atrophic following epithelial invasion in human tumors and that degradation of the basal membrane is an important factor in this process. At the ultrastructural level, different SMC phenotypes occur in prostatic tissues during epithelial invasion. Interconversion between these phenotypes is suggested and a probable relationship among them is proposed.

Prenatal testosterone exposure as a model for the study of endocrine-disrupting chemicals on the gerbil prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hormonal Oscillations During the Estrous Cycle Influence the Morphophysiology of the Gerbil (Meriones unguiculatus) Female Prostate (Skene Paraurethral Glands)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disorders related with ageing in the gerbil female prostate (Skene's paraurethral glands)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Microscopic evaluation of proliferative disorders in the gerbil female prostate: Evidence of aging and the influence of multiple pregnancies

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Short-term stromal alterations in the rat ventral prostate following alloxan-induced diabetes and the influence of insulin replacement

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Aging effects on the mongolian gerbil female prostate (Skene's paraurethral glands): Structural, ultrastructural, quantitative, and hormonal evaluations

Different from the classic view, the prostate is not a gland exclusive to the male, also being an organ of the female genital system presenting morphofunctional similarity between human and rodent. Thus structural, ultrastructural, morphometric-stereological features of the female prostate (Skene's paraurethral gland) and steroid serological levels were evaluated during young, adult, and senile ages in the Mongolian gerbil. The morphofunctional precocity of the female gland in comparison with the male gland occurring in young gland is probably associated with the female circulating steroid levels. The hormonal imbalance in senesce coincides with its susceptibility to histopathological lesions, such as epithelial hypertrophy, metaplasia, and intraepithelial neoplasia. Differently than that of males, the aging degeneration of the female gland involves the accumulation of lipofuscin granules. However, the alterations in senile prostate did not damage its functionality. These analyses reinforce the use of this experimental model for the comprehension of glandular morphofunctional aspects with special attention to senescence. Thus, the appreciation of this organ becomes relevant to avoid future discomfort to women's health.