Chapter 23 Hormonal Regulation and Integration of Mammalian Metabolism 23 1 Hormones Diverse Structures for Diverse Functions Processes regulated by hormones o Maintenance of blood pressure blood volume and electrolyte balance o Embryogenesis o Sexual differentiation development and reproduction o Hunger eating behavior digestion and fuel allocation Neuroendocrine system the system that coordinates metabolism in mammals The 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 used to study hormone action RIA a sensitive assay for peptide hormones that is Hormones 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 interactions a process by which you can quantify hormone receptor o 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 hormone o Cytosolic o 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 enzymes o A receptor tyrosine kinase is activated by the extracellular hormone o A receptor guanylyl cyclase is activated and produces the second messenger cGMP o A change in membrane potential results from the opening or closing of a hormone gated ion channel o An adhesion receptor on the cell surface interacts with molecules in the extracellular matrix and conveys information to the cytoskeleton o 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 responses o 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 days o Alter gene expression Hormones Are Chemically Diverse Chemical structures and modes of action o peptide amine and eicosanoid hormones act from outside the target o steroid vitamin D retinoid and thyroid hormones enter the cell and cell via surface receptors act through nuclear receptors cyclase o nitric oxide enters the cell and activates a cytosolic enzyme guanylyl 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 body and diffuse to neighboring target cells binding to receptors on the surface o paracrine hormones that are released into the extracellular space o autocrine hormones that effect the same cell that releases them Peptide Hormones o May have from 3 to 200 or more amino acid residues o Include Somatostatin Insulin Glucagon Calcitonin All the hormones of the hypothalamus and pituitary o Synthesized on ribosomes in the form of longer precursor proteins then packaged into secretory vesicles and proteolytically cleaved to form the active peptides disulfide bonds a small protein with two polypeptide chains joined by two o Insulin Synthesized in the pancreas as preproinsulin o 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 Norepinephrine adrenaline noradrenaline o Water soluble o Synthesized from tyrosine o Produced in the brain o Function as neurotransmitters but epinephrine and norepinephrine are also hormones synthesized and secreted by the adrenal glands o Act through surface receptors to generate intracellular second messengers Eicosanoid Hormones o Prostaglandins thromboxanes and leukotrienes o Derived from arachidonate o Are produced when needed o Most cells can produce them and many can respond to them through specific plasma membrane receptors o Paracrine hormones that are secreted into the interstitial fluid and act on nearby cells o Prostaglandins Promote the contraction of smooth muscle Mediate pain and inflammation in all tissues Steroid Hormones o Adrenocortical hormones and sex hormones o Synthesized from cholesterol in several endocrine tissues o Travel through bloodstream bound to carrier proteins o Formation usually involves cytochrome P 450 enzymes o Two general types Glucocorticoids primarily affect the metabolism of Mineralocorticoids regulate the concentrations of electrolytes carbohydrates in the blood o Androgens and estrogens are synthesized in the testes and ovaries Affect sexual development behaviour and a variety of other reproductive and nonreproductive functions o 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 sunlight o Calcitrol is produced from vitamin D in the liver and kidneys Retinoid Hormones retinoid receptors o Regulate the growth survival and differentiation of cells via nuclear o Retinol is synthesized from carotene in the liver o All tissues are retinoid targets o Retinoic acid regulates the synthesis of proteins essential for growth or differentiation Thyroid Hormones metabolism Nitric Oxide NO o T4 and T3 are synthesized from thryoglobulin o Act through nuclear receptors to stimulate energy yielding o A relatively stable free radical synthesized from molecular oxygen and the guanidinium nitrogen of arginine Catalyzed by NO synthase o Found in many tissues and cell types Neurons Macrophages Hepatocytes Myocytes of smooth muscle Endothelial cells of the blood vessels Epithelial cells of the kidney o Acts near its point of release o Activates guanylyl cyclase which
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