Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration.

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

Gestational and lactational xenoestrogen exposure disrupts morphology and inflammatory aspects in mammary gland of gerbil mothers during involution.

In the mammary gland (MG), the developmental window for gestational/lactational differentiation and growth is highly vulnerable to hormonal disruption. Here we describe that the MG involution process in female gerbil mothers is delayed by bisphenol A (BPA) exposure during gestation and lactation. The process is directly influenced by changes in expression of extracellular matrix proteases MMP-2, MMP-9, and FAP, and the incidence of collagen and elastin is reduced after 7 and 14 days of weaning. A pro-inflammatory environment in the late involution process was confirmed by higher expression of TNF-α, COX-2 and phospho-STAT3 n the MG stroma, allied to increases in the incidence of macrophages and mast cells. These aspects impacted the proliferative pattern of epithelial cells, which decreased on the 14th post-weaning day. These data confirm that the milk production window of susceptibility is vulnerable to the impact of BPA, which promotes a suggestive pro-tumoral microenvironment during mammary involution.

Hormone receptor expression in aging mammary tissue and carcinoma from a rodent model after xenoestrogen disruption.

AIMS: Hormone receptors are the main markers applied for prognosis of breast cancer subtypes. Among modulators, exogenous chemical agents known as endocrine disruptors interact with certain receptors, triggering molecular pathways or increasing their expression. Bisphenol A (BPA), a xenoestrogen, interacts with several hormone receptors. Thus, our aim was to characterize the hormone receptor status in the mammary gland (MG) of aged female Mongolian gerbils exposed to BPA in pregnancy and lactation. METHODS: We evaluated the expression of receptors for estrogens (ERα and ERß), progesterone (PR), prolactin (PRL-R), HER2/ErbB2, and androgen (AR) in normal and hyperplastic mammary tissue and in carcinomas developed after BPA exposure. KEY FINDINGS: BPA-exposed MG presented increased ERα, whereas ERß, PR, and PRL-R showed lower expression. AR and HER2/ErbB2 showed similar expression in normal and hyperplastic tissue from control, vehicle, and BPA groups. Both receptors were found in cytoplasm and nucleus in BPA-induced carcinoma. We demonstrate the presence of EZH2 expression, an epigenetic and epithelial-mesenchymal transition (EMT) marker, with a high H-score in BPA-exposed MG, which was associated with poor prognosis of cancer. Co-localization of ERα and EZH2 was present in normal and carcinoma features, corroborating the installation of ERα-positive mammary cancer associated with the EMT process. Enhanced EZH2 in BPA-exposed mammary tissue could decrease ERß expression and promote tumorigenesis progress through HER2/ErbB2. SIGNIFICANCE: The present study proposes the Mongolian gerbil as an experimental model for mammary carcinogenesis studies, based on BPA disruption that triggers a phenotype of increased ERα/HER2 positivity and depletion of ERß/PR expression.