Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca²⁺ signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling.

Compounds that trigger breast cancer onset and establishment are of great interest in biological research. Endocrine disruptors are relevant because they initiate carcinogenesis by changing endocrine pathways. Bisphenol A (BPA), as a ubiquitous xenoestrogen, is largely associated with dysfunctions in the female reproductive system and associated organs. This study proposes an investigation of the mammary gland (MG) in aged Mongolian gerbil (Meriones unguiculatus) mothers after their exposure to BPA in two windows of morphophysiological plasticity: pregnancy and lactation. A low dose (50 μg/kg), and a high dose (5000 μg/kg) were considered and results showed few differences between them. As expected, we observed contrasts among control and BPA-exposed MG. The control groups presented a regressive phase with high apoptotic activity and elastic stroma. However, BPA damaged mammary tissue and provoked multifocal carcinoma development supported by an apparent epithelial-mesenchymal transition (EMT) and reactive stroma establishment. BPA remodeled stromal fibers deposition and enhanced the recruitment of tumor-associated cells, contributing to a tumoral microenvironment. Overexpression of TGF-β1 was induced by BPA in the epithelial compartment of exposed MG and increased expression of metalloproteinases (MMP-2, MMP-3, MMP-9) was present in carcinoma cells. In conclusion, exposure of mothers to BPA during the gestational/lactational window of susceptibility leads to carcinogenic impacts with aging.

No abstract

Bisphenol A (BPA) and cadmium (Cd) are environmental pollutants that are implicated in potential reproductive effects, including damage to the prostate gland. Their action during puberty requires analysis to determine the relationship of these compounds with the testosterone peak that occurs during this phase. This study evaluated whether exposure to BPA and Cd during puberty can cause changes in the morphology, proliferation and cell death and androgen receptor (AR) immunostaining of the ventral prostates of normal and castrated male gerbils (Meriones unguiculatus), considering an acute exposure to the chemicals and evaluation after short (52d) and long (120d) periods. Generally, morphometric-stereological results demonstrated that administration of BPA and Cd (individually or in combination) increased epithelial height, smooth muscle layer (SML) thickness and nuclear area and perimeter, and that these parameters were reduced in castrated animals. In addition, these groups showed important inflammatory processes but not prostate lesions. The proliferation/death rates of prostatic cells obtained by PCNA and TUNEL immunostaining demonstrated increased cell death in the 52d groups; in contrast, the gland acquired a more proliferative nature in the 120d groups. AR immunostaining showed that BPA and Cd compounds interact with ARs in different ways depending on the evaluated period and the hormonal profile of the animal. We conclude that BPA and cadmium are important agents in changing the morphology, proliferation and death of prostatic cells, in addition to interacting with ARs in different patterns. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 48-61, 2017.

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.