Progesterone (PRG) is a key cyclical reproductive hormone that has a significant impact on female organs in vertebrates. It is mainly produced by the corpus luteum of the ovaries, but can also be generated from other sources such as the adrenal cortex, Leydig cells of the testes and neuronal and glial cells. PRG has wide-ranging physiological effects, including impacts on metabolic systems, central nervous systems and reproductive systems in both genders. It was first purified as an ovarian steroid with hormonal function for pregnancy, and is known to play a role in pro-gestational proliferation during pregnancy. The main function of PRG is exerted through its binding to progesterone receptors (nPRs, mPRs/PAQRs) to evoke cellular responses through genomic or non-genomic signaling cascades. Most of the existing research on PRG focuses on classic PRG-nPR-paired actions such as nuclear transcriptional factors, but new evidence suggests that PRG also exerts a wide range of PRG actions through non-classic membrane PRG receptors, which can be divided into two sub-classes: mPRs/PAQRs and PGRMCs. The review will concentrate on recently found non-classical membrane progesterone receptors (mainly mPRs/PAQRs) and speculate their connections, utilizing the present comprehension of progesterone receptors.
ABSTRACT Cerebral cavernous malformations (CCMs) are neurological disorders that make individuals more susceptible to hemorrhagic stroke. The Mexican-Hispanic population has a higher prevalence of both CCMs and metabolic syndrome (MetS), which is also associated with hemorrhagic stroke. A study was conducted with 184 Mexican-Hispanic CCM subjects and age- and sex-matched Hispanic and non-Hispanic white controls. The CCM cohort had a higher proportion of epilepsy and hemorrhagic stroke but a lower proportion of MetS. Higher blood pressure and fasting glucose levels were observed in the CCM cohort. MetS and epilepsy were associated with increased odds of hemorrhagic stroke among elderly CCM patients, and increased systolic blood pressure was significantly linked to increased odds of hemorrhagic stroke in the CCM cohort. To minimize the risk of hemorrhagic stroke, it is important to manage blood pressure and comorbidities like MetS and epilepsy in CCM patients, particularly those older than 50. SUMMARUY What is already known about this subject Metabolic Syndrome (MetS) is widely associated with cardiovascular conditions, including stroke, The association between MetS and ischemic stroke is well established The relationship between MetS and hemorrhagic stroke remains unclear Currently, one two studies explored the relationship between MetS and hemorrhagic stroke in CCM patients; one n sporadic CCM (sCCM) and one in familial CCM cases, with inconsistent results. What are the new findings In this study, a strong association was observed between systolic blood pressure (SBP) and hemorrhagic stroke in the CCM cohort, independent of obesity or fasting glucose levels. This study also suggests that MetS is associated with hemorrhagic stroke among CCM patients, specifically in the older age group. How might it impact on clinical practice in the foreseeable future This study demonstrates many of the unique characteristics of symptomatic CCMs within the Mexican-Hispanic population Our results suggests that of Mexican-Hispanic CCM subjects are at a greater risk for hemorrhagic stroke and epilepsy than other ethnic groups. This study highlights the importance of reducing blood pressure and managing comorbidities such as MetS and epilepsy in CCM patients, especially those who are older than 50 years to minimize the risk of hemorrhagic stroke among CCM subjects
Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood–brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood–brain barrier (BBB) permeability. Within the NVU, tight junctions (TJs) and adherens junctions (AJs) between endothelial cells play a critical role in regulating the permeability of the BBB. Disruptions to these junctions can compromise the BBB, potentially leading to a hemorrhagic stroke. Understanding the molecular signaling cascades that regulate BBB permeability through EC junctions is, therefore, essential. New research has demonstrated that steroids, including estrogens (ESTs), glucocorticoids (GCs), and metabolites/derivatives of progesterone (PRGs), have multifaceted effects on blood–brain barrier (BBB) permeability by regulating the expression of tight junctions (TJs) and adherens junctions (AJs). They also have anti-inflammatory effects on blood vessels. PRGs, in particular, have been found to play a significant role in maintaining BBB integrity. PRGs act through a combination of its classic and non-classic PRG receptors (nPR/mPR), which are part of a signaling network known as the CCM signaling complex (CSC). This network couples both nPR and mPR in the CmPn/CmP pathway in endothelial cells (ECs).
It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells. However, the mechanisms responsible for zinc accumulation and the consequences of zinc dysregulation are poorly understood. In this review, we detailed cellular zinc regulation/dysregulation under the influence of varying levels of sex steroids and breast cancer tumorigenesis to try to better understand the intricate relationship between these factors based on our current understanding of the CmPn/CmP signaling network. We also made some efforts to propose a relationship between zinc signaling and the CmPn/CmP signaling network.
