Effects of Cortisol 1 Stimulates gluconeogenesis from AAs in liver 2 Stimulates glycogen synthesis in liver long term effects a 3 Stimulates protein catabolism especially in muscle 4 Inhibits protein synthesis in most cells a Breaks down prt primarily in SM aa s release are targeted towards the liver Cortisol will aslo inhibit aa uptake in other cells besides the liver 5 But increases protein synthesis in liver 6 Stimulates lipolysis in adipose tissue liberates free FAs for energy metabolism or can be converted into glucose 7 Directly opposes the action of insulin Generally hyperglycemic lipolytic ketogenic Indirect effects via glucagon GH epi Especially lipolytic actions of GH and epi Cortisol Defends against hypoglycemia Builds up long term stores of glycogen so that catecholamines can cause short term release Epi from adrenal medulla and norepi from sympathetic nerves Mobilizes energy from stores during fasting starvation Other Cortisol Actions Anti inflammatory o synthesis of arachidonic acid o synthesis of eicosanoid paracrines Immunosuppression o cytokine release o Ab production o leukocyte activity Ca2 loss from body o Bone demineralization osteoporosis evolutionary trade off o renal Ca2 excretion o intestinal Ca2 absorption Effects on brain o Mood changes o Memory and learning o Enhances memory of traumatic events Cortisol Pathologies Hypercortisolism Cushing s Syndrome 1 Primary pversecreting in Adrenal gland o Oversecreting adrenal tumor not under control of ACTH 2 Secondary resides in Ant Pituitary o Oversecreting pituitary tumor ACTH no negative feedback o control Cushing s Disease 3 Iatrogenic o Physician caused due to glucocorticoid therapy Hypocortisolism 1 Primary a Undersecretion of all adrenal steroids often due to autoimmune attack Addison s Disease Also inherited defects in specific synthetic enzymes cause various symptoms 2 Secondary a Impairment of anterior pituitary or hypothalamus 3 Acute a Abrupt withdrawal of therapeutic glucocorticoids 4 Ectopic ACTH syndrome Small cell carcinoma of lung involves ACTH and ADH secreting neuroendocrine cells Thyroglobulin molecules are rich in tyrosine rich Iodine comes from blood diffuses out to EC pumped in through Na dependent I symporter Iodide builds up in cell o Comes out through apical membrane through Pendrin Iodide Cl exchanger o Iodide is very reactive spontaneously reacts with tyrosine to form Iodine atoms attach to Tyrosine When both of C are iodinated becomes diiodotyrosine Monoiodotyrosine when one escapes o T4 weak thyroid activity mainly a precursor for T3 o T3 comes from random chance of 1 double iodinated and one single iodinated thyroglobulin Free T3 T4 would immediately diffuse out cannot be stored in aqueous membrane Stored as part of structure or protein to not diffuse When TSH signals to thyroid cell to endocytose cell degridative enzymes break down thyroglobulin T3 and T4 are released from protein backbone 90 T4 9 is T3 1 is rT3 diffuse out of cell via MCT enter plasma and bind to specific Thyroid Binding Globulin renders the hormone capable of being soluble or non specific proteins albumin most abundant o Lipophylic hormones steroid hormones and thyroid hormones T3 Thyroid hormone receptor stimulates metabolism slow to develop long lasting widespread o T4 prohormone ring on right next to r group in inter ring other is called outer ring o T3 3 Iodines singly iodinated outer ring o rT3 inner ring is singly iodinated Inactive isomer Target cell can adjust production of final active hormone according to its needs at the time Deiodinase D membrane bound enzymes in target cells that takes I off T4 o D1 3 inside plasma membrane D3 inactivates thyroid hormones in target cells T4 rT3 T3 T2 D1 can deiodonate both rings outer ring T3 inner ring rT3 o D2 outside of smooth ER membrane Turns on T3 production makes cell more responsive to thyroid hormone Activator of prohormone Regulated enzyme by ubiqutination attaching ubiquinone targets enzyme for destruction in the proteasome D2 can also remove iodine from outer ring of rT3 or create T2 also inactive o These enzymes Thyroid Hormone Effects 1 Stimulate a Na K ATPase b oxidative phosphorylation c protein synthesis d lipolysis 2 Increased O2 consumption and heat production because of metabolic activity 3 Increased respiration heart rate stroke volume cardiac output 4 Stimulate appetite 5 Required for bone brain in utero development a Mother thyroid hormone stimulates fetus growth for first 10 weeks Maternal TH does not cross palcenta well so requires fetus to make its own hormone Necessary for body growth cannot grow without thyroid hormones o Thyrotropin Releasing Hormone TRH Ant Pit TSH circulates and stims thyroid follicle cell Iodide necessary in thyroid gland for feedback o Primary Hypothyroidism lethargic cold sleepy children permanent retardation of phys mental growth High TSH with no suppression so thyroid gland grows to large proportions goiter o Most common thyroid disease Hashimotos Disease cytotoxic T cells attack thyroid follicle cells so have symptoms of hypothyroidism Lack of native feedback so TSH stims growth of thyroid gland o Treat with thyroid hormone supplementation o Graves disease hyperthyroid condition autoimmune circulating autoantibodies that mimic TSH stimulates TSH receptor which activates thyroid follicle and pumps out a lot of thyroid hormone o Causes excessive heat production sweat lose weight with high metabolism but eat a lot might gain weight irritable CARDIOVASCULAR heart beats too fast Exophthalmos fat in back of eye grows too much and pushes eyes forward o Goiter in Graves Disease Not easily treated Gamma ray