UBC Theses and Dissertations
Local glucocorticoid production by the mouse immune and nervous systems Hamden, Jordan E.
Glucocorticoids are steroid hormones primarily produced by the adrenal glands and released into the bloodstream to coordinate animal development and a myriad of physiological processes. Adrenal glucocorticoid production greatly increases in response to stressors, except during a period in early development in altricial species, termed the stress hyporesponsive period. During the stress hyporesponsive period, blood glucocorticoid levels are very low and have a blunted response to some stressors. Glucocorticoids are also locally produced by organs such as the bone marrow, thymus, spleen, and brain. Within such organs, glucocorticoids can be synthesized from precursors or regenerated from the inactive metabolite; however, it is not known which route is more important. Local glucocorticoid production allows organs to independently regulate glucocorticoid levels based on demand and this may be of particular importance during the stress hyporesponsive period when blood glucocorticoid levels are low. In this dissertation, I present a series of studies examining production of glucocorticoids in lymphoid organs and brain across development and in response to an acute stressor. Briefly, I report that 1) glucocorticoids are locally elevated in lymphoid organs and specific brain regions in neonatal mice, but not adolescent or adult mice, 2) within the brain, glucocorticoid levels are more modular during early development and more coupled between regions during adulthood, 3) local glucocorticoid production increases greatly in response to a stressor during the stress hyporesponsive period, but less afterwards. Altogether, lymphoid organs and specific brain regions produce glucocorticoids. Local glucocorticoid production is of increased importance during the stress hyporesponsive period as it allows tissues to independently regulate local levels, provides benefits of high glucocorticoid levels where needed, and helps avoid the deleterious effects of glucocorticoids where they are not required.
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