Physiological functions of glucocorticoids in stress and their relation to pharmacological actions.
Almost any kind of threat to homeostasis or stress will cause plasma glucocorticoid levels to rise. The increased levels have traditionally been ascribed the physiological function of enhancing the organism’s resistance to stress, a role well recognized in glucocorticoid therapy. How the known physiological and pharmacological effects of glucocorticoids might accomplish this function, however, remains a mystery. A generalization that is beginning to emerge is that many of these effects may be secondary to modulation by glucocorticoids of the actions of numerous intercellular mediators, including established hormones, prostaglandins, and other arachidonic acid metabolites, certain secreted neutral proteinases, lymphokines, and a variety of bioactive peptides. These mediators participate in physiological mechanisms–endocrine, renal, immune, neural, etc.–that mount the first line of defense against such challenges to homeostasis as hemorrhage, metabolic disturbances, infection, anxiety, and others. Contrary to the traditional view that glucocorticoids enhance these defense mechanisms, however, it has become increasingly clear that glucocorticoids at moderate to high levels generally suppress them. This paradox, which first emerged when glucocorticoids were discovered to be anti-inflammatory agents, remains a major obstacle to a unified picture of glucocorticoid function. We propose that stress-induced increases in glucocorticoid levels protect not against the source of stress itself but rather against the body’s normal reactions to stress, preventing those reactions from overshooting and themselves threatening homeostasis. This hypothesis, the seeds of which are to be found in many discussions of particular glucocorticoid effects, immediately accounts for the paradox noted above. Furthermore, it provides glucocorticoid physiology with a unified conceptual framework that can accommodate such apparently unrelated physiological and pharmacological effects as those on carbohydrate metabolism, inflammatory processes, shock, and water balance. It also leads us to suggest that some of the enzymes rapidly induced by glucocorticoids, such as glutamine synthetase, detoxify mediators released during stress-induced activation of primary defense mechanisms. These mediators would themselves lead to tissue damage if left unchecked.
Chronic Stress- Surging Glucocorticoids
In some ways, we are not so different from a zebra on the Serengeti. If we are threatened with bodily harm, just like the zebra being chased by a lion, our adrenal glands kick into high gear and secrete adrenalin and glucocorticoid hormones. These hormones can keep us alive in an emergency. Blood rushes to our most needed organs (heart, lungs, muscles). Digestion shuts down and we stop salivating. Our attention gets very focused. We have no need to get an erection or urinate (save that for later if we live). These fight or flight hormones can keep us alive in an emergency. But they are meant to turn off quickly when the event has passed. Where humans differ from animals is that we can suffer from chronic worry and keep those hormones surging through our system for days on end. Heart disease, depression, diabetes, obesity, immune dysfunction, learning disorders, headaches, irritable bowel syndrome,… what do these diseases of modern man have in common? They have all been linked to chronic stress. And chronic stress means we have cortisone affecting our organs and cells when it should be turned off.
Robert Sapolsky, a brilliant Stanford neurobiologist and author of “Why Zebras Don’t Get Ulcers” and “A Primates Memoir” has studied baboons in Africa for decades. Doing elegant controlled studies of these social animals, he has come to some amazing conclusions that may explain how humans respond to chronic stress. He found low ranking baboons with fewer opportunities in baboon culture and less control of their lives had more stress hormones and more disease. He also found that bab