Chapter 23 - Hormonal Regulation and Integration of Mammalian Metabolism23.1 Hormones: Diverse Structures for Diverse Functions- Processes regulated by hormones:o Maintenance of blood pressure, blood volume, and electrolyte balanceo Embryogenesiso Sexual differentiation, development, and reproductiono Hunger, eating behavior, digestion, and fuel allocation- Neuroendocrine system – the system that coordinates metabolism in mammalsThe Detection and Purification of Hormones Requires a Bioassay- Once a physiological effect of a hormone is discovered, a quantitative bioassay for the hormone can be developed- radioimmunoassay (RIA) – a sensitive assay for peptide hormones that is used to study hormone actionHormones Act through Specific High-Affinity Cellular Receptors- the specificity of hormone action results from structural complementarity between the hormone and its receptor- the high affinity of receptor-signal interaction allows cells to respond to very low concentrations of hormone- Statchard analysis – a process by which you can quantify hormone-receptor interactionso Yields a quantitative measure of affinity and the number of hormone-binding sites in a preparation of receptor- Three loci for the encounter between hormone and receptor:o Extracellular – water-soluble peptide and amine hormones Receptor undergoes a conformational change that triggers the downstream effects of the hormoneo Cytosolico Nuclear – water-insoluble hormones The hormone-receptor complex itself carries the message and interacts with DNA to alter the expression of specific genes- The intracellular consequences of hormone-receptor interaction are of six general types:o A second messenger generated inside the cell acts as an allosteric regulator of one or more enzymeso A receptor tyrosine kinase is activated by the extracellular hormoneo A receptor guanylyl cyclase is activated and produces the second messenger cGMPo A change in membrane potential results from the opening or closing of a hormone-gated ion channelo An adhesion receptor on the cell surface interacts with molecules in the extracellular matrix and conveys information to the cytoskeletono A steroid or steroidlike molecule causes a change in the level of expression of one or more genes, mediated by a nuclear hormone receptor protein- Hormones that act through plasma membrane receptors generally trigger very rapid physiological or biochemical responseso Lead to a change in the activity of a preexisting enzyme in the cell by allosteric mechanisms or covalent modification- The thyroid hormones and the sex hormones promote maximal responses in their target tissues only after hours or even dayso Alter gene expressionHormones Are Chemically Diverse- Chemical structures and modes of action:o peptide, amine, and eicosanoid hormones act from outside the target cell via surface receptorso steroid, vitamin D, retinoid, and thyroid hormones enter the cell and act through nuclear receptorso nitric oxide enters the cell and activates a cytosolic enzyme, guanylyl cyclase- They way they get from their point of release to their target tissue:o endocrine – hormones that are released into the blood and carried to target cells throughout the bodyo paracrine – hormones that are released into the extracellular space and diffuse to neighboring target cellso autocrine – hormones that effect the same cell that releases them, binding to receptors on the surface- Peptide Hormones o May have from 3 to 200 or more amino acid residueso Include: Insulin Glucagon Somatostatin Calcitonin All the hormones of the hypothalamus and pituitaryo Synthesized on ribosomes in the form of longer precursor proteins, then packaged into secretory vesicles and proteolytically cleaved to form the active peptideso Insulin – a small protein with two polypeptide chains joined by two disulfide bonds Synthesized in the pancreas as preproinsulino All peptide hormones act by binding to receptors in the plasma membrane and causing the formation of a second messenger in the cytosol, which changes the activity of an intracellular enzyme- Chatecholamine Hormones o Catecholamines : Epinephrine (adrenaline) Norepinephrine (noradrenaline)o Water-solubleo Synthesized from tyrosineo Produced in the brain o Function as neurotransmitters, but epinephrine and norepinephrine are also hormones, synthesized and secreted by the adrenal glandso Act through surface receptors to generate intracellular second messengers- Eicosanoid Hormones o Prostaglandins, thromboxanes, and leukotrieneso Derived from arachidonateo Are produced when needed o Most cells can produce them and many can respond to them through specific plasma membrane receptorso Paracrine hormones that are secreted into the interstitial fluid and acton nearby cellso Prostaglandins Promote the contraction of smooth muscle Mediate pain and inflammation in all tissues- Steroid Hormones o Adrenocortical hormones and sex hormoneso Synthesized from cholesterol in several endocrine tissueso Travel through bloodstream bound to carrier proteinso Formation usually involves cytochrome P-450 enzymeso Two general types: Glucocorticoids primarily affect the metabolism of carbohydrates Mineralocorticoids regulate the concentrations of electrolytes in the bloodo Androgens and estrogens are synthesized in the testes and ovaries Affect sexual development, behaviour, and a variety of other reproductive and nonreproductive functionso All steroid hormones act through nuclear receptors to change the level of expression of specific genes- Vitamin D Hormone o Obtained in the diet or by photolysis of 7-dehydroxholesterol in skin exposed to sunlighto Calcitrol is produced from vitamin D in the liver and kidneys- Retinoid Hormones o Regulate the growth, survival, and differentiation of cells via nuclear retinoid receptorso Retinol is synthesized from -carotene in the livero All tissues are retinoid targetso Retinoic acid regulates the synthesis of proteins essential for growth or differentiation- Thyroid Hormones o T4 and T3 are synthesized from thryoglobulino Act through nuclear receptors to stimulate energy-yielding metabolism- Nitric Oxide (NO)o A relatively stable free radical synthesized from molecular oxygen andthe guanidinium nitrogen of arginine Catalyzed by NO synthaseo Found in many tissues and cell types: Neurons Macrophages Hepatocytes Myocytes
View Full Document
Unlocking...