Lecture 25 03182024 Metabolic Hormones PDF

Outline Learning Objectives: Introduction: anabolism vs. catabolism ✔ Carbohydrate, lipid and protein metabolism ✔ Metabolic rate (MR) ✔ Factors affecting metabolic rate (e.g. size, activity, temperature, insulin, glucagon, other hormones) Metabolism ✔ ✔ ✔ ✔ ✔ 49 Metabolic rate Factors influencing m...

Outline Learning Objectives: Introduction: anabolism vs. catabolism ✔ Carbohydrate, lipid and protein metabolism ✔ Metabolic rate (MR) ✔ Factors affecting metabolic rate (e.g. size, activity, temperature, insulin, glucagon, other hormones) Metabolism ✔ ✔ ✔ ✔ ✔ 49 Metabolic rate Factors influencing metabolic rate 4) hormones - insulin - glucagon - epinephrine - glucocorticoids - thyroid hormone Metabolism 50 Metabolic hormones Epinephrine and Glucocorticoids – Adrenal Gland Adrenocorticotropic horomne (ACTH) Metabolism (e.g. glucocorticoids) 51 Metabolic hormones Epinephrine - also known as adrenaline - hormone secreted by the adrenal medulla in response to stress (e.g. “fight-or-flight” response) Functions: ↑ lipolysis and fatty acid release from adipose ↑ glycogenolysis in liver and muscle, and ↑ hepatic gluconeogenesis ↑ glycolysis in muscle ➥ overall effect: ↑ glucose production & fatty acid availability for fuel ↑ ATP production in muscle ⬇ insulin, ⬆ glucagon secretion to reinforce metabolic effects of epinephrine Metabolism 52 Metabolic hormones Glucocorticoids - Cortisol - steroid hormone secreted by the adrenal cortex mainly in response to stress Functions: - counterbalances insulin ↑ blood glucose concentration at the expense of protein and fat stores ↑ hepatic gluconeogenesis and ↑ glycogenolysis ↑ protein degradation to form free amino acids ↑ lipolysis in adipose tissue Metabolism 53 Metabolic hormones Glucocorticoids - Cortisol Cortisol Secretion from Hypothalamic-Pituitary-Adrenal (HPA) Axis: 1) corticotropin-releasing hormone (CRH) release from the hypothalamus is stimulated in response to stress (physical, chemical, physiological, and psychological) - CRH secretion also under circadian control (↑ secretion in morning, ↓ night) 2) CRH stimulates secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary 3) ACTH then stimulates cortisol secretion from the adrenal cortex Metabolism 4) cortisol exerts it metabolic effects and suppresses secretion of CRH and ACTH secretion (negative feedback) 54 Metabolic hormones Glucocorticoids - Cortisol Cortisol Secretion from Hypothalamic-Pituitary-Adrenal (HPA) Axis: Similar to Fig. 7-12, p289 Fig. 7-21, p307 Metabolism 55 Metabolic hormones Thyroid Hormone (TH) Two iodine-containing hormones: thyroxine (T4) and triiodothyronine (T3) - follicular cells of the thyroid synthesize and secrete thyroglobulin into the colloid where the thyroglobulin is iodinated Fig. 7-16, p298 Metabolism 56 Metabolic hormones Thyroid Hormone (TH) Steps in synthesis, storage and secretion of TH: 1. TH synthesis takes place on the thyroglobulin (Tg) produced by thyroid follicular cells and transported by exocytosis to the colloid 1 Na+ + Na NKA K+ K+ 2 TPO 2. Thyroid captures iodide (I-) from the blood and transfers it to the colloid via an iodide pump, involving NKA coupled with symporter Metabolism Häggström, Mikael. "Medical gallery of Mikael Häggström 2014". Wikiversity Journal of Medicine 1 (2). Similar to Fig. 7-17, p299 57 Metabolic hormones Thyroid Hormone (TH) Steps in synthesis, storage and secretion of TH: 3. At luminal membrane, Ienters colloid through a channel and, at the colloid/ thyroid follicle interface, thyroperoxidase (TPO) oxidizes I- to iodine (I0) Na+ + Na NKA K+ TPO 4. I0 is very reactive and iodinates Tg at tyrosine residues, forming mono(MIT) or di-iodotyrosine (DIT) K+ 3 4 Häggström, Mikael. "Medical gallery of Mikael Häggström 2014". Wikiversity Journal of Medicine 1 (2). Similar to Fig. 7-17, p299 Metabolism 58 Metabolic hormones Thyroid Hormone (TH) Steps in synthesis, storage and secretion of TH: 5. Conjugation process between iodinated tyrosine molecules to form TH (MIT+DIT = T3 and DIT+DIT = T4) Na+ + Na NKA K+ K+ TPO 6. Iodinated Tg re-enters follicular cell by endocytosis and T3 and T4 liberated by proteases and is then released into the blood Metabolism 6 5 Häggström, Mikael. "Medical gallery of Mikael Häggström 2014". Wikiversity Journal of Medicine 1 (2). Similar to Fig. 7-17, p299 59 Metabolic hormones Thyroid Hormone (TH) Two iodine-containing hormones: thyroxine (T4) and triiodothyronine (T3) - follicular cells of the thyroid synthesize and secrete thyroglobulin into the colloid where the thyroglobulin is iodinated ➥ iodinated thyroglobulin re-enters the follicular cells by endocytosis, and is cleaved by proteases into T3 and T4 and then released into the blood - secreted T4 : T3 ratio ~20:1 - T3 is ~10x more potent than T4 - T4 is converted to T3 at the liver, kidneys, heart Metabolism Fig. 7-16b, p298 60 Metabolic hormones Thyroid Hormone (TH) Functions: - primary determinant of MR ↑ basal metabolic rate (BMR), ↑ heart rate ➥ thermogenic - increases the rate of ATP breakdown and decreases the efficiency of ATP synthesis (energy lost as heat) - modulates the effects of other hormones (e.g. insulin, epinephrine, growth hormone) by permissiveness ➥ increases cell sensitivity to effects of other hormones by up-regulating number of receptors available on target cells - affects protein, carbohydrate and fat metabolism in a concentration-dependent manner Metabolism 61 Metabolic hormones Thyroid Hormone (TH) TH Secretion from Hypothalamic-Pituitary-Thyroid (HPT) Axis: 1) thyrotropin-releasing hormone (TRH) is tonically secreted from hypothalamus ➥ neuronal stimuli (e.g. stress, such as cold or starvation) can influence TRH release 2) TRH stimulates release of thyroid-stimulating hormone (TSH) from the anterior pituitary 3) TSH in turn stimulates the release of thyroid hormones (T4 and T3) from the thyroid gland 4) THs exert their metabolic effects and suppress secretion on TRH and TSH secretion (negative feedback) Metabolism 62 Metabolic hormones Thyroid Hormone (TH) TH Secretion from Hypothalamic-Pituitary-Thyroid (HPT) Axis: cold nutritional stress Similar to Fig. 7-19, p303 Metabolism 63