Corticosteroids: the ‘floating switches’ that ‘ignites’ the physiological ‘engine’

 Nature has quaint ways of  doing its job. The nervous system of an organism takes cues from the environment and initiates a well crafted, precisely timed sequence of events (See someone nudging the ball and set it rolling down the hill) to adjust to the surroundings. The environment is a bountiful of stressors. In addition to the promptly generated neuronal response, a slow and sustained adaptive mechanism drives the forces of ‘struggle and survival’ in the living organism. The Hypothalamus-Pituitary takes the ‘lead and first role’ in ‘pushing the ball down the hill’ and a relay run begins. The corticotropin releasing hormone from the hypothalamus ‘runs’ to the pituitary; the pituitary in turn continues the relay run by releasing corticotropin (also commonly known as ACTH); ACTH ‘runs’ to the adrenal cortex which releases the adrenal corticosteroids. Adrenal corticosteroids are of two types- the glucocorticoids and the mineralocorticoid. The most well known endogenous glucocorticoid and mineralocorticoid are cortisol and aldosterone respectively. The ‘run’ ‘stops’ at the adrenal cortex from where the adrenal cortisol hormones are disseminated to every nook and corner of the body. The actions of corticosteroids are widespread but tissue dependent. The corticosteroids act as ‘floating switches’ ready to ‘ignite’ the ‘flames’ of cellular processes in the cells which have the ‘matching switches’ in the respective cells. The ‘matching switches’ are the glucocorticoid receptors (GR) and the mineralocorticoid receptors (MR). Both the GRs and MRs are intracellular cytoplasmic receptors. The GRs are ubiquitous and are responsible for translation of most of the actions of the glucocorticoids through the glucocorticoid response elements (GRE). The MRs are present in kidneys, hippocampus and colon. The glucocorticoids can also bind with MRs, in fact, with much greater affinity than the mineralocorticoid and can result in manyfold higher activation of mineralocorticoid response elements (MRE). Fortunately, nature has bestowed a mechanism to prevent the excessive action of glucocorticoids in such cells. The glucocorticoids are selectively inactivated by the enzyme 11 hydroxysteroid dehydrogenase and only the mineralocorticoid are available for action.