Ovariectomy increases the phenotypic plasticity of the female prostate epithelium in the Mongolian gerbil (Meriones unguiculatus).

The female prostate is a reproductive gland that typically presents a morphology similar to that of the male gland and is highly developed in female Mongolian gerbils. Two main cell populations compose the epithelium gland: basal and secretory luminal cells. However, during postnatal development, diverse secretory cell phenotypes are distributed among the typical ones. Prostate homeostasis is under the control of sexual hormones, such as oestrogen and progesterone. After hormonal deprivation the female gland undergoes several morphophysiological changes. The objective of this study was to identify and characterise, structurally and ultrastructurally, the cellular heterogeneity of the female prostate epithelium in normal conditions and after ovariectomy. Histological routine stains, such as haematoxylin-eosin, periodic acid-Schiff and silver impregnation, as well as immunocytochemical techniques were used to enable identification of the different cell types. Some secretory cells types were identified and characterised as mucinous, basophil, clear, ciliated, droplet, spumous and neuroendocrine cells. Population tally data showed that the hormonal suppression caused by ovariectomy resulted in a decrease in the proportions of basophil and clear cells and an increase in spumous cells. Thus, the secretory epithelial cells of the female gerbil prostate are not morphologically and functionally uniform, presenting a phenotypical plasticity according to the hormonal environment in which they operate.

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

The present study examined the response of the prostate epithelium of senescent gerbils submitted to orchiectomy and with or without steroidal blockade. Animals were divided into five groups, all surgically castrated except the control group composed of intact animals. In the experimental groups, doses of flutamide and/or tamoxifen were applied for 1, 3, 7 and 30 days postcastration. The structural methods applied reveal that castration, whether associated or not with anti-steroidal drugs, promoted short- and long-term decrease in wet and relative weights of the prostate. The quantitative decline of epithelial compartment proportion observed at the end of treatment was due to the sum of slight changes in the epithelium and lumen. The apoptotic index had risen significantly at 1 day and declined at 7 days postcastration. Androgen receptor (AR) expression decreased after 3 days of hormonal ablation, coinciding with the highest levels of apoptosis and cell proliferation observed in all treated groups. The majority of cells remained differentiated in all groups due to CK 8/18 expression. Some animals remained with injuries such as carcinomas and adenocarcinomas after hormonal ablation. In the latter a mixture of AR-positive and AR-negative cells was identified. Microinvasive carcinomas found in the group treated for 30 days consisted of PCNA-positive, inflammatory and non-proliferating cells. Low apoptosis incidence and bcl-2 positive cells were observed in these lesions. The treatments promoted a reduction of lesions in older gerbils, but treatment-resistant tumours will improve understanding of the events that lead to hormone resistance.

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

The female organs, which are regulated by steroid hormones, are targets of studies especially those related to senescence. However, although the female prostate is an organ influenced by hormones and susceptible to lesions, there is still little information about its histopathology. Thus, given the morphophysiological similarity between the prostate in women and female gerbils, the present study aimed to identify the spontaneous histopathological changes in this rodent to provide contributions to the understanding of lesions that also affect the human female prostate. The structural, ultrastructural, immunohistochemical, morphometric-stereological and serological aspects, as well as the quantification of the incidence, multiplicity and percentage of acini affected by different lesions were analyzed. Benign prostate lesions including hyperplasia, prostatitis, microcalculi and calculi; preneoplastic lesions like dysplasias; premalignant lesions, such as high grade prostatic intraepithelial neoplasia as well as malignant ones, specifically adenocarcinoma, were identified in the adult gland, but they were intensified during senescence, which is possibly due to the imbalance among steroid hormone levels. Although clinical attention focuses on other urogenital organs, the real condition of the histopathological injuries in the human female prostate should be considered. A serious preventive work regarding the female prostate could be applied in the gynaecological context in order to monitor the gland and avoid possible disturbances to women's health and consequently provide better quality of life.

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

The present work aims to evaluate the response of the adult gerbil female prostate (paraurethral glands) and ovaries to short-term exposure to antiestrogenic agents, consisting of daily oral doses of letrozole (1 mg kg(-1) day(-1)) or intradermal doses of tamoxifen (1 mg/kg) every other day for 21 days. The serum levels of testosterone and estradiol were monitored, and the prostates and ovaries collected for structural, ultrastructural, and immunocytochemical analyses. The letrozole treatment resulted in increases of serum testosterone levels and secretory activity as well as in glandular hyperplasia and dysplastic growth, simulating the effects caused by the exogenous androgens. The effects caused by tamoxifen indicate that this endocrine agent acted as an estrogenic agonist on the prostate, causing glandular hypertrophy, secretory activity decrease, and the development of prostatic lesions. Therefore, it is possible to conclude that the letrozole and tamoxifen therapies result in a series of complex effects that endanger the physiology of hormone-dependent organs, including the female prostate and ovaries. The hormonal imbalance caused by administration of these drugs resulted in considerable changes in prostatic morphology, in a manner very similar to what occurs during the development of prostatic lesions in aged postmenopausal women. Thus, these therapies must be chosen carefully since long-term treatments can result in female prostate dysplasic lesions.

Testosterone stimulates growth and secretory activity of the female prostate in the adult gerbil (Meriones unguiculatus).

The prostate of the female gerbil (Meriones unguiculatus) is similar to the human female prostate (Skene gland) and, despite its reduced size, it is functional and shows secretory activity. However, virtually nothing is known about its physiological regulation. This study was thus undertaken to evaluate the behavior of the gerbil female prostate in a hyperandrogenic condition. Adult females received subcutaneous injections of testosterone cypionate (1 mg/kg body weight every 48 h) up to 21 days. Circulating levels of testosterone and estradiol were monitored, and the prostate and ovaries subjected to structural and immunocytochemical analyses. The treatment resulted in sustained high levels of circulating testosterone, and caused a transient increase in estradiol. There was an increase in epithelial cell proliferation accompanied by significant reorganization of the epithelium and an apparent reduction in secretory activity, followed by a progressive increase in luminal volume density and accumulation of secretory products. Immunocytochemistry identified the expression of androgen receptor and a prostate-specific antigen (PSA)-related antigen in prostatic epithelial cells. A circulating PSA-related antigen was also found, and its concentration showed strong negative correlation with circulating estrogen. Epithelial dysplasia was detected in the prostate of treated females. Analysis of the ovaries showed the occurrence of a polycystic condition and stromal cell hyperplasia. The results indicate that testosterone has a stimulatory effect on the female prostate, inducing epithelial cell proliferation, differentiation, secretory activity, and dysplasia. The results also suggest that prostatic growth and activity, polycystic ovaries, and ovarian stromal cell hyperplasia are related to a hyperandrogenic condition in females.