The hypothalamus–pituitary–adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in coordinating responses of this system to stressors. The cytokine interleukin-1β (IL-1β), mimicking infection, robustly activates these CRH neurons via a noradrenergic input arising from the nucleus tractus solitarii (NTS). In late pregnancy, HPA axis responses to stressors, including IL-1β, are attenuated by a central opioid mechanism that auto-inhibits noradrenaline release in the PVN. Here we show that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsiveness to IL-1β in pregnancy. In late pregnancy, inhibition of 5α-reductase (an allopregnanolone-synthesizing enzyme) with finasteride restored HPA axis responses (rapidly increased pPVN CRH mRNA expression, ACTH, and corticosterone secretion) to IL-1β. Conversely, allopregnanolone reduced HPA responses in virgin rats. In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5α-reductase and 3α-hydroxysteroid dehydrogenase) was increased in the hypothalamus as was mRNA expression in the NTS and PVN. Naloxone, an opioid antagonist, restores HPA axis responses to IL-1β in pregnancy but had no additional effect after finasteride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism. Indeed, allopregnanolone induced opioid inhibition over HPA responses to IL-1β in virgin rats. Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnant rats finasteride decreased proenkephalin-A mRNA expression in the NTS. Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis responses to immune challenge. This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other brain systems in pregnancy.

Ovarian cancer is one of the most common cancers in women and the most concerning issues in gynecological oncology in recent years. It is postulated that many factors may contribute to the development of ovarian cancer, including hormonal imbalance. Estrogens are a group of hormones that have an important role both in physiological and pathological processes. In ovarian cancer, they may regulate proliferation, invasiveness and epithelial to mesenchymal transition. Estrogen signaling also takes part in the regulation of the biology of the tumor microenvironment. This review summarizes the information connected with estrogen receptors, estrogens and their association with a tumor microenvironment. Moreover, this review also includes information about the changes in estrogen receptor expression upon exposition to various environmental chemicals.

The intestinal barrier is the main barrier against all of the substances that enter the body. Proper functioning of this barrier guarantees maintained balance in the organism. Mycotoxins are toxic, secondary fungi metabolites, that have a negative impact both on human and animal health. It was postulated that various mycotoxins may affect homeostasis by disturbing the intestinal barrier. Claudins are proteins that are involved in creating tight junctions between epithelial cells. A growing body of evidence underlines their role in molecular response to mycotoxin-induced cytotoxicity. This review summarizes the information connected with claudins, their association with an intestinal barrier, physiological conditions in general, and with gastrointestinal cancers. Moreover, this review also includes information about the changes in claudin expression upon exposition to various mycotoxins.

Zearalenone (ZEA), a mycotoxin produced in the genus Fusarium, binds to estrogen receptors (ER) and is therefore regarded as an endocrine disruptor. ZEA has also been found to modulate the proliferation and apoptosis of prostate cancer cells in a dose-dependent manner. This study evaluates whether the effect of a low dose of ZEA (0.1 and 0.001 nM) on the invasion and migration of prostate cancer cell line PC3 is associated with ERs expression. The invasion and migration was evaluated by modified Boyden chamber assay, scratch assay, gelatin zymography, Real Time qPCR (RTqPCR) and Western blot. The involvement of ERs was evaluated with the selective ER antagonists: estrogen receptor α (ERα) antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) and estrogen receptor β (ERβ) antagonist 4-[2–phenyl-5,7–bis (trifluoromethyl) pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP). ZEA was found to modulate cell motility dependent on estrogen receptors, particularly ERα. Increased cell migration and invasion were associated with increased MMP-2 and MMP-9 activity as well as the up-regulation of the EMT-associated genes vimentin (VIM), zinc finger E-box-binding homeobox 1/2 (ZEB1/2) and transforming growth factor β 1 (TGFβ1). In conclusion, ZEA might modulate the invasiveness of prostate cancer cells dependently on ERα expression.