Hormones

Explain the role of glucocorticoids on fuel metabolism:

"Counterregulatory" hormones that protect the body from insulin-induced hypoglycemia. Cortisol is the major GC. - GCs have diverse actions that promote survival in times of stress. - GCs inhibit DNA, RNA and protein synthesis and stimulate the degradation of these macromolecules (thereby making fuel available in preparation for "fight or flight" actions) - GCs stimulate lipolysis in adipose tissue and the release of amino acids from muscle protein. - In liver, GCs stimulate gluconeogenesis and the synthesis of glycogen. The breakdown of liver glycogen is stimulated by epinephrine.

Describe the role of GH and the effects of GH on target tissues:

- GH effects are mediated by insulin-like growth factors (IGFs) - Rise in IGF-I levels contributes to cell multiplication and differentiation - IGF-I inhibits GHRH release and stimulates somatostatin release. On target tissues: - increases lipolysis in adipose tissue, which increases the availability of fatty acids for oxidation - decreases the oxidation of glucose and amino acids - increases amino acid uptake into muscle cells, thereby increasing muscle protein synthesis - stimulates gluconeogenesis and glycogen production in the liver

Describe the effect of excess production of GH:

- Gigantism if GH is secreted in excess before the closure of the growth centers of the ends of long bones - acromegaly if excess GH is chronically secreted after the closer of these centers.

Define IGFs and their role in GH signaling:

- The hypothalamus produces GHRH, which stimulates somatotrophs in the anterior pituitary to release GH - GH binds to cell surface receptors and stimulates IGF production and release by liver and other tissue. - IGF binds cell surface receptors and stimulates the phosphorylation of proteins that lead to cell division and growth

Explain the physiological role of somatostatin:

- inhibits insulin secretion - suppresses secretion of growth hormone (GH) - Suppresses secretion of thyroid-stimulating hormone (TSH). - Mechanism is to inhibit adenylate cyclase, reducing cAMP and inhibition of PKA activation

Describe the physiological effects of thyroid hormone:

Effects on the Liver-increases glycolysis and cholesterol synthesis, increase in the synthesis of bile salts and triglycerides. Effect on the Adipocyte-Increased lipolysis and glycerol release Effects on Muscle-increases glucose uptake by muscle cells, stimulates protein synthesis and growth of muscle, increases glycolysis in muscle cells Effects on Pancreas-increases the sensitivity of the b-cells of the pancreas to stimuli that normally promote insulin release Effects on the Sympathetic Nervous-increases the release of norepinephrine. Norepinephrine stimulates the uncoupling protein thermogenin in brown adipose tissue, resulting in increased heat

Explain the effects of Epinephrine on fuel metabolism and pancreatic function:

Fuel metabolism is directly influenced by the actions of epinephrine and norepinephrine in the liver, the adipocyte and the skeletal muscle. - counterregulatory hormones that have metabolic effects directed toward mobilization of fuels from their storage sites for oxidation by cells to meet the increased energy requirements of acute and chronic stress. - As long as stress persists, they suppress insulin secretion ensuring that fuel fluxes will continue in the direction of fuel use rather than storage. - Epinephrine (Epi) increases the secretion of glucagon through pancreatic a-cells. - inhibits insulin release through pancreatic b-cells Epi stimulates glycogen breakdown in muscle and liver, gluconeogenesis in liver and lipolysis in adipose tissue.

Describe the physiologic effects of insulin and glucagon on metabolism?

Insulin: •stimulates the storage of glycogen in liver and muscle •stimulates the synthesis of fatty acids and triacylglycerol and their storage in adipose tissue. •insulin stimulates the synthesis in various tissue of >50 proteins, some of which contribute to the growth of the organism. •insulin released from b-cells suppresses glucagon release from the a-cells of the pancreas. Glucagon: •Glucagon is one of several counterregulatory (contrainsular) hormones •synthesized as a large precursor protein call proglucagon •Proglucagon is produced in the a-cells of the islets of Langerhans in the pancreas and in the L-cells of the intestines. •Glucagon is cleaved from proglucagon in the blood. •Pancreatic glucagon has a half-life of 3-6 minutes •Promotes glycogenolysis, gluconeogenesis, and ketogenesis by stimulating the generation of cAMP in target cells

Briefly describe the synthesis of thyroid hormone:

Iodide is transported out of the blood and into thyroid acinar cells where it is oxidized to form an iodinating species -thyroid peroxidase Iodination of tyrosyl residues on the protein thyroglobulin (Tgb) forming iodotyrosines. Coupling of residues of monoiodotyrosine and diiodotyrosin in TgB form residues of T3 and T4. Proteolytic cleavage of Tgb releases free hormone. Tgb is synthesized in thyroid follicular cells and secreted into the colloid. Ionization and coupling of tyrosine residues in Tgb produce T3 and T4 T3 and T4 are released from Tgb via pinocytosis and lysosomal action (cleavage)

Describe the regulation of thyroid hormone:

TRH from the hypothalamus stimulates the release of TSH from the anterior pituitary, which stimulates the release of T3 and T4 from the thyroid. T4 is converted to T3 in the liver and other cells. T3 inhibits the release of TSH from the anterior pituitary and of TRH from the hypothalamus