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Lecture 2

Lecture 2 Hormones

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University of Toronto St. George
Michelle French

Lecture 2 Text Notes Classification of Hormones - classified according to different schemes – source, release controlled by brain/not by brain, bind to G protein-coupled receptors/tyrosine kinase-linked receptors/intracellular receptors, chemical classes, etc. - peptide hormones • peptide/protein hormones can range from small (three amino acids long) to large (proteins or glycoproteins) • if a hormone is not a steroid hormone nor an amino acid derivative, then it must be a peptide or a protein • all hormones in this class are called peptide hormones for the sake of simplicity • made in tissues all over the body - steroid hormones • all have a similar structure • derived from cholesterol • made in only a few organs • adrenal cortex makes several types of steroid hormones - amino acid-derived/amine hormones • small molecules made from either tryptophan or tyrosine Peptide Hormones - synthesis, storage, release • synthesis/packaging of peptide hormones into membrane-bound secretory vesicles is similar to other proteins • initial peptide comes off ribosome – large inactive protein called a preprohormone • preprohormone – contains one or more copies of a peptide hormone • peptide hormone – signal sequence that directs the protein into the lumen of the rough endoplasmic reticulum • inactive preprohormone moves through endoplasmic reticulum and the Golgi complex • signal sequence is removed and creates a prohormone • prohormone – smaller, inactive molecule, similar to preprohormone • in Golgi complex, prohormone is packed into secretory vesicles with the proteolytic enzymes • proteolytic enzymes – chop prohormone into active hormone and other fragments • process is called post-translational modification • secretory vesicles with the peptides are stored in the cytoplasm of the endocrine cell until cell receives a signal for secretion • secretion – vesicles move to cell membrane and release contents by calcium-dependent exocytosis • co-secretion – release of all the peptide fragments created by the prohormone, together, into the extracellulat fluid - modification of prohormones • some prohormones (TRH, thyrotropic-releasing hormone) contain multiple copies of the hormone • some prohormones (pro-opiomelanocortin) split into three active peptides plus an inactive fragment • fragments can be clinically useful • example – proinsulin is cleaved into active insulin and an inactive fragment (C-peptide) • meansurement of the C-peptide levels in the blood of diabetics is used to monitor the amount of insulin the pancreas is producing - transport and half-life • peptide hormones are water-soluble • dissolve easily in extracellular fluid for transport in body • half-life for peptide hormones is quite short (several minutes) • if response to a peptide hormone must be over a long period of time then the hormone must be continually secreted - cellular mechanism • peptide hormones are lipophobic – usually unable to enter target cell • bind to surface membrane receptors • hormone-receptor complex initiates cellular response through a signal transduction system • many peptide hormones work through cAMP second messenger systems • some peptide hormone receptors (insulin receptors) have tyrosine kinase activity or work through other signal transduction pathways • cell response to peptide hormones is usually quick because second messenger systems modify existing proteins • changes triggered by peptide hormones – opening/closing membrane channels, modulating metabolic enzymes/transport proteins • some peptide hormones have longer-lasting effects when second messenger system activates genes and directs synthesis of new proteins Steroid Hormones - adrenal cortex – outer portion of the adrenal glands, makes several types of steroid hormones - adrenal glands sit atop of the kidneys - gonads produce the sex steroids – estrogens, progesterone, androgens - pregnant women – placenta is also a source of steroid hormones - synthesis and release • cells that secrete steroid hormones have high amounts of smooth endoplasmic reticulum • steroids are synthesized in the smooth endoplasmic reticulum • steroids are lipophilic and diffuse easily across membranes – in parent cell and target cell • steroid-secreting cells cannot store hormones in secretory vesicles but synthesize the hormone as needed • stimulus activates endocrine cell and precursors in the cytoplasm are converted into active hormone • hormone concentration in cytoplasm rises and hormones move out by diffusion - transport and half-life • steroid hormones are not very soluble in plasma/body fluids • most steroid hormones found in blood are bound to protein-carrier molecules • some hormones have specific carriers (corticosteroid-binding globulin) and others bind to general plasma proteins (albumin) • binding to a carrier protects the steroid hormone from enzymatic degradation – results in extended half-life • example cortisol, hormone produced by the adrenal cortex, has half- life of 60-90 minutes • binding blocks entry into target cells however • carrier –steroid complex remains outside the cell • carrier proteins are lipophobic and cannot diffuse through the membrane • only unbound hormone can diffuse into the target cell • only a tiny amount of unbound steroid hormone necessary to produce a reaction - cellular mechanism • ultimate destination of steroid receptor-hormone complexes is the nucleus • complex acts as a transcription factor in the nucleus – binds to DNA and wither activates or represses one or more genes • genomic effect – alteration of gene activity (often by hormones) • time lag between hormone-receptor binding and first measurable biological effect – when steroid hormones activate genes to direct production of new proteins • steroid hormones do not mediate reflex pathways that require rapid responses • some steroids cause rapid nongenomic responses in addiction to slow genomic effects – several steroid hormones have been discovered to have cell membrane receptors linked to signal transduction pathways (the way peptide hormones do) Amine Hormones - thyroid hormones are made from two tyrosine molecules plus iodine atoms - two groups of tyrosine-based hormones – catecholamines and thyroid hormones - catecholamines – neurohormomes that bind to cell membrane receptors the way peptide hormomes do (example: epinephrine, norepinephrine, dopamine) - thyroid hormones – produced by butterfly-shaped thyroid gland beneath the Adam’s apple, behave more like steroid hormones with intracellular receptors that activate genes Control of Hormone Release - there are basic patterns of reflex pathways to the control pathways for hormones - classification of hormones by reflex pathways – pathways that regulate their secretion - reflex pathway components – stimulus, sensor, input signal, integration of input signal, output signal, one or more targets, response - endocrine/neuroendocrine reflex – output signal is a hormone or neurohormone - some hormones have clear stimuli that initiate release (insulin secretion to i
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