Glucocorticoids: exemplars of multi‐tasking

Abstract

Well over 80 years ago Philip Smith described the beneficial clinical effects of adrenocortical extracts in animal models of adrenal insufficiency. In the ensuing years, scientists across the globe have sought to understand the mechanisms by which adrenal hormones and their synthetic analogues produce their complex and varied actions. Particular attention has focused on the glucocorticoids, partly because they have a vital place in the treatment of inflammatory and autoimmune disorders but also because dysregulation of the secretion and/or activity of endogenous glucocorticoids is increasingly implicated in a number of common disorders that pose a growing clinical burden, such as obesity, type II diabetes, the metabolic syndrome, hypertension and depression. This review considers some of the key advances that have been made in our understanding of the physiology, pathology and pharmacology of the glucocorticoids. Emphasis is placed on the molecular mechanisms of glucocorticoid signalling and the complex mechanisms that regulate the access of steroids in the systemic circulation to their receptors in their various target cells and tissues. In addition, consideration is given to the irreversible 'organisational' actions of glucocorticoids in perinatal life and to the potential role of the steroids in the aetiology of disease.

Adrenal peripheral clock controls the autonomous circadian rhythm of glucocorticoid by causing rhythmic steroid production

“…Moreover, there exist 2 types of GC receptors with distinctive affinities and capacities, and these are believed to be differentially activated at the circadian peak and nadir of circulating ligand levels (2). The observations that the expression of at least 10% of all genes is influenced by GC (2), and that the cyclicities of some hepatic genes can be affected by an intact adrenal gland and/or GC signaling (43,44), strongly support this notion. Also, the circadian rhythm of certain discrete brain regions is dependent on GC signaling, implying that even higher brain functions can be directly influenced by the adrenal rhythm (40,45).…”

“…It modulates gluconeogenesis, lipid metabolism, cardiovascular tone, inflammation, and immune functions. Importantly, GC mediates behavioral adaptations to external cues, because its level responds sensitively to stress and to circadian rhythm (1,2).…”

Blockade of nitric oxide synthesis stimulates the activity of adrenal cortex

“…Glukokortikoidni hormoni deluju na skoro sve ćelije u organizmu preko: mineralokortikoidnih (tip 1) receptora visokog afiniteta i široko rasprostranjenih glukokortikoidnih (tip 2) receptora (GR) slabijeg afiniteta, koji selektivno vezuju glukokortikoidne hormone (7). Oba tipa receptora funkcionišu kao transkripcioni faktori, zavisni od liganda.…”

Koçlara deksametazon uygulamasının kan oksidatif durum ve prostaglandin F2? metaboliti düzeyine etkisi

“…İnsanlarda kortizol dominant olarak bulunurken, koyunlarda her ikisi de dominant olarak salgılanır. Canlıda hemen hemen bütün organ ve doku üzerinde etkileri bulunmaktadır (Buckingham 2006, Srinivasan ve ark 2013. Kan basıncı, sı-vı-elektrolit denge, hücresel enerji metabolizması ve immun fonksiyon üzerine etkisi bulunur (Macfarlane ve ark 2008, Gensler 2012.…”