Hello everyone. Welcome back to my Coursera class. This is session two, the second session of week seven. So, this session is about stress response, some metabolic adaptation in response to stress. Many types of stress can influence our systems, like many aspect of human physiology, mainly those stress responses are relayed and regulated through the brain circuits. So, in particular, the hypothalamus sense stress, and then they release a hormone like corticotrophin-releasing hormone, or factor called CRF, and from hypothalamic region to pituitary region, another area for stress processing inside the brain. Adrenocorticotrophic hormones ultimately released from the pituitary into blood flow. So finally, in particular, the kidney tissues sense those ACTH and then activated, and stress hormones indeed are released from adrenal gland, either cortex or medulla regions to trigger the production of a series of hormones in particular, adrenal gland medulla region dependent hormones like two catecholamines like norepinephrine and epinephrine. The epinephrine is another word like adrenaline. And those hormones are released and then they mediate physiologic stress responses. So, this is structure of epinephrine. And when those hormones are released from a stressful condition by the adrenal medulla regions of your kidney, and those epinephrine binds to specific receptor, localizing the target cell plasma membrane, and then activated epinephrine receptors trigger the elevation of cyclic AMP, which is the ATP are derived signaling metabolites, and cyclic AMP further activate protein kinase A called PKA, and cyclic AMP dependent protein kinase. And this cyclic AMP protein kinase A signaling cascade ultimately regulate many types of enzymes and transcription factors to regulate metabolic reactions and gene expression profiles. So finally, to change, to adapt the target cell physiology and metabolic processes against stressful queues and stressful environment. All right. This is the signalling action of epinephrine. So, when epinephrine level is increased and those epinephrine affect influence, influences many peripheral tissues, the physiological metabolic reactions are quite changed and then adapted in response to stress. So, for example, epinephrine can drive the degradation of glycogen and glycogenolysis, so glycogen concentration increased and then glycogen synthesis those anabolic reactions are quite inhibited. And the pancreas, epinephrine can prevent the secretion of insulin, and rather increase the glucagon hormone, and muscular tissues, glycolytic rate is going to be increased, and then fat molecules, triacylglycerols will be mobilized from adipose tissues into peripheral tissues like liver. So, ultimately, those biochemical changes can lead to the increase of blood glucose level, and the liver, the glucose output will be increased. So, one sentence summary is very clear. Blood glucose level will be promoted by the actions of epinephrine stress hormone in response to stressful condition. So, in addition to epinephrine, there is another stress hormone called corticosteroid. Again, ACTH hormones from pituitary stimulate adrenal regence of kidney, and then those hydrophobic corticosteroid like cortisol levels will be increased. And this hydrophobic corticosteroid, they can just pass, diffused into the target cells, these molecules are very hydrophobic. So, their receptors, those corticosteroid receptors, just exist inside the cells and inside the nucleus, so like corticosteroid receptor or a glucocorticoid receptor, those steroid hormone receptors actually in many cases, they are just transcription factors, which means the interaction between corticosteroid and hormone receptors can drive the specific target gene expression, and those gene expression affect cellular physiology in response to stress. So, again, so when glucocorticoid level is going up, another stress hormone, in that case, the best known function for glucocorticoid is the promotion of gluconeogenesis in the liver, and then glucose uptake will be decreased. And again, is like epinephrine, triacylglycerol mobilization will be promoted, and then protein degradation will be accelerated. So, again, the ultimate physiologic action of glucocorticoid is very clear, blood glucose level will be increased, and on top of this, even amino acid level will be increased because protein degradation will be facilitated by glucocorticoid stress hormone. So, when you think about the physiologic outcome and metabolic situation after the stress induced hormone release and their signaling actions, very clear, glucose level will be increased. And those stress induced physiologic metabolic changes and metabolic adaptations finally help and favors the survival of host under the acute life-threatening situation, because glucose is very, very important nutrient for neural functions as well as the cardiac functions, right? The problem is this one. However, the modern lifestyle, many types of stressors become very, very chronic, not that acute. So, there are many issues of stress: financial issues, a lot of pressures, family issues and social pressures, whatever. The thing is when these stressors cause timely and chronically affect a host, I mean the human that is a chronic stress responses is not that beneficial but rather becomes very harmful. And predisposing, metabolically predisposing people to obesity and many metabolic syndromes. So, I think as you can understand right now epinephrine or those glucocorticoids, overall, they are trying to release blood glucose concentration, and they drive adiposity, and also they trigger the onset of insulin resistance, and collectively, finally, metabolic deregulation situation will be developed. This is the biochemical and the metabolic principles of how chronic stress can influence a human physiology.