How Hormones Influence Composition and Physiological Function of the Brain-Blood Barrier

Abstract

Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord

“…It is reported that sex hormones exert a neuroprotective role that influences the permeability of the BBB. BBB cells play a complex role, ensuring the separation of circulating substances within the blood from nerve tissue, thus providing a well-balanced microenvironment in the brain [3]. In addition to endothelial cells, this role is also provided by other associated cells, including astroglia and pericytes [59].…”

“…Chronic stress is frequently related to chronic pain conditions, such as fibromyalgia, irritable bowel syndrome, or neuropathic pain [1,2]. Pain conditions are neuroplastic alternations of the electrical properties that can cause increased excitability of neurons, as well as substantial changes in the permeability of the blood-brain barrier (BBB) [3][4][5]. Epidemiological studies and systematic reviews have pointed out a higher incidence of chronic pain conditions in women, but there is not enough information about the mechanisms underlying these sex-specific differences [6][7][8].…”

“…Oestrogen influences the propagation of stress-associated visceral Life 2021, 11, 1330 2 of 23 hypersensitivity and has been proposed as a basis for various chronic pain conditions [9,10], while testosterone inhibits the hypothalamic-pituitary-adrenal axis response [11] providing a possible explanation for a lower prevalence of some pathological conditions related to chronic stress in men [1]. In addition, sex hormones modulate the permeability of the BBB [3]. The BBB is a highly selective and dynamic physical divider of the circulatory system and neural tissue, heavily susceptible to local changes [12].…”

The microbiota and gut-brain axis

“…There are several more peptide hormone that are interacting with the BBB, for example ghrelin and leptin, which are among others responsible for hunger and homeostasis. The permeability of the BBB can be also influenced by cytokines, which are not crossing the BBB from the circulation, but are also expressed in the endothelial cells of the BBB and control the homeostasis of energy transfer(21). Thus the microbiome is able to change permeability.…”