Hormones and Target Tissues

Transcription

1 Hormones and Target Tissues

2 The hypothalamus is the coordination center of the endocrine system Hypothalamus is a small region of the forebrain in animals with skulls It receives and integrates nerve signals from the central nervous system It synthesizes small peptide hormones oxytocin and vasopressin It synthesizes several factors that regulate the function of anterior pituitary

3 Pituitary release of hormones target other glands Posterior pituitary (neurohypophysis) contains the end of axons from the hypothalmus produces short peptide hormones made in the hypothalmus (vasopressin, oxytocin) Anterior pituitary (adenohypophysis) is endocrine organ that receives releasing factors from hypothalamus via blood vessels Produces long peptide hormones called tropins Activates second targets: adrenal cortex, thyroid, ovaries/testes

4 More About the Hypothalmus- Pituitary System

5 Posterior Pituitary Hormones Oxytocin and Vasopressin Oxytocin promotes: contraction of smooth muscle of the uterus during labor milk release from the mammary gland Vasopressin promotes: water reabsorption in kidneys to maintain salt balance constriction of blood vessels; increases blood pressure Both hormones: play roles in social behavior such as pair bonding; these CNS effects do not involve pituitary secretion

6 Two Hormones of the Posterior Pituitary Gland: Oxytocin and Vasopressin

7 Cortisol cascade illustrates amplification and feedback inhibition Fear, infection, hypoglycemia, etc. send electric signal to hypothalmus ~ng of corticotropin-releasing hormone Anterior pituitary releases g corticotropin Adrenal gland releases mg cortisol Cortisol end-product can inhibit these steps

8 Cortisol Cascade

9 2. Metabolism:Division of Labor of Tissues

10 Pathways of Carbohydrate, Amino Acid, and Fat Metabolism Illustrated in Earlier Chapters

11

12 insulin

13 Overview of metaboilsm 단백질합성 Glycogenesis Glycogenolysis S70S6K mtor Glu Insulin Glucagon Epinephrine F-1,6-bisphosphatase Phosphofructokinase Glut4 IR IRS GProtein F-6-P Glu PI 3 K GSK3β Akt Phosphoenolpyruvate kinase((pepck) FOXO1,HNF-4 GS SREBP-1,2 Glycogen 합성 camp PKA PGC1 α PPAR α/β Pyr dehydrogenase Chol synthesis HMG-CoA reductase Cholesterol

14 Glucokinase Hexokinase Metabolic pathways for glucose 6-phosphate in the liver

15 식간 glu level 조절 Metabolism of amino acids in the liver

16 -albumin 공복시심장 (1/3), 뇌 (2/3) E 원 Metabolism of fatty acids in the liver

17 The liver adapts to changing metabolic conditions Portal vein carries nutrients to liver Hepatocytes turn nutrients into fuel Hepatocyte enzymes turn over quickly Enzymes increase or decrease with changes in diet and needs of other tissues

18 Liver cells have unique features Hepatocytes have GLUT2 transporter Allows passive diffusion of glucose in and out Hepatocytes have glucokinase (hexokinase IV) Has higher K m than other hexokinases 10 mm vs. 4 mm So glucose-6-phosphate (g6p) isn t made when glucose low (other tissues need it) Not inhibited by g6p So g6p can be made continually ** GLUT4: muscle, adipose tissue; GLUT1:RBC, Brain

19 Other Sugars Processed by Liver Fructose, galactose, mannose convert to g6p G6p is the transfer station in the liver Can be made by multiple pathways Can have multiple fates Fates depend on the needs of other tissues!

20 Fates Available to G6p in the Liver 1) Dephosphorylate to yield free glucose to send to other tissues 2) Make into liver glycogen 3) Enter glycolysis, make acetyl CoA then ATP for hepatocytes themselves 4) Enter glycolysis, make acetyl CoA to be made into fatty acids then TAGs 5) Enter pentose phosphate pathway to yield NADPH and ribose-5-phosphate

21 Fates for Glucose 6- Phosphate in the Liver

22 Fates Available to Amino Acids in the Liver 1) Make into proteins for liver and other tissues 2) Make into hormones, nucleotides 3) Make into CAC intermediates or pyruvate: a. for gluconeogenesis b. convert pyruvate to acetyl-coa for: i. liver cell energy ii. conversion to lipids

23 Metabolism of Amino Acids in the Liver

24 Fates Available to Fatty Acids (FA) in the Liver 1) Use FA to synthesize liver lipids 2) Oxidize FA to acetyl-coa and NADH a. CAC and oxphos ATP - FA are primary fuel for liver b. Excess acetyl-coa ketone bodies for brain, heart, etc. in carbohydrate restriction, fasting c. Some acetyl-coa cholesterol 3) Convert FA to phospholipids 4) Convert FA to TAGs for storage 5) Carry FA to heart and muscle for oxidation

25 Ketone bodies are made from acetyl-coa Include -hydroxybutyrate, aceteoacetate, and acetone Made when oxaloacetate pools are insufficient to condense with acetyl-coa Can enter brain (unlike most FA, which are bound to serum albumin) Are oxidized for energy in the place of or to supplement glucose Can provide up to 70% of energy for heart during prolonged fasting

26 Metabolism of Fatty Acids in the Liver

27 Review of Liver Functions Provide glucose and ketones for other organs Process amino acids into urea, etc. Store nutrients (Fe ion, fat-soluble vitamins) Detoxify and solubilize organic compounds via cytochrome P450 system

28 Composition of Two Types of Fat Tissue White adipose tissue (WAT) Made of large spherical cells (30 70 m) filled with one lipid droplet Mitochondria and nucleus are squeezed to a layer near membrane Brown adipose tissue (BAT) Smaller (20 40 m), not round Have several lipid droplets Have more mitochondria More cytochrome content gives it a brown color

29 Adipocytes of WAT and BAT

30 Two Types of Fat Function WAT serves as fuel storage BAT expresses uncoupling protein UCP1 (thermogenin) Enables H + gradient in mitochondrial to be dissipated Energy is released as heat process is called thermogenesis Keeps organs warm in low-temp environments BAT is primarily in newborns, around kidneys, spine, etc.

31 Functions of Adipocytes Carry out glycolysis through oxphos Convert acetyl-coa into fatty acids But in humans, the liver is the preferred place for FA synthesis Use FA to make TAGs From intestinal lipids via chylomicrons From the liver via VLDL Release FA when other tissues need them Skeletal muscle, heart

32 Hormones work quickly on adipocytes Lipases hydrolyze TAGs to release FA Accelerated by epinephrine camp-dependent cascade phosphorylation of perilipin Gives hormone-sensitive lipase (HSL) access to lipid droplet Insulin decreases activity of HSL Glyceroneogenesis(PEPCK)

33 Hormones trigger mobilization of stored triacylglycerols Epinephrine

34 Brown adipose tissue can be synthesized even in adults At birth, BAT is abundant Surrounds organs, provides warmth during adaptation to ambient temperature BAT declines in childhood But preadipocytes even in adults can be induced to become BAT Via cold exposure See Fig 성인남자 : 3% 로여자 7% 로감소 * Beige fat

35 FGF21 and browning mitochondria - Browning is to stimulate the development of 'brown-like' adipocytes (so called beige cells) in white adipose tissue (WAT) uni-locular browning FGF21 & adiponectin multi-locular - Browning is a novel promising therapeutic target for metabolic diseases such as type 2 diabetes and dyslipidemia - FGF21 has been suggested as an important regulator of browning by increasing UCP1, PGC-1α, and thermogenic markers - Some studies have reported that adiponectin also induces browning

36 Distribution of BAT

37 Muscle (Myocytes) Two Types Slow-twitch (red muscle, Type 1): 장거리 Fed by many blood vessels Rich in mitochondria to provide energy via slow and steady oxphos Fast-twitch (white muscle, Type 2): 단거리 Fewer mitochondria and lower O 2 delivery Uses ATP faster and fatigues faster due to greater demands (more tension, etc.) combined with reduced O 2 delivery Endurance training can increase mitochondria

38 Fuels that Skeletal Muscle Uses Can use glucose, fatty acids or ketone bodies. Resting muscle relies on fatty acids Active muscles use glucose and ketone bodies

39 Sources of Glucose and ATP for Skeletal Muscle Muscle glycogen glucose 6-phosphate Yields 3 ATPs, not 4 (as in glycolysis) Glycogen breakdown skips ATP-dependent hexokinase rx Then pyruvate lactate to create NAD + to enable glycolysis to continue Phosphocreatine Acted on by creatine kinase to release ATP

40 Energy Sources for Muscle Contraction