08 07 2012 8 7 12 Survey of Hormones clock Melatonin amine oxytocin Pineal Gland melatonin secretion In response to darkness to reset biological Hypothalamus cluster of neurons Peptide hormones Vasopressin ADH and Pituitary gland posterior extensions of the hypothalamic neurons o Anterior peptides Master gland Secretes several hormones that regulate other glands including gonads thyroid adrenal Trophic hormones Thyroid TH development of embryo and regulates metabolism Iodinated amines Parathyroid produce PH essential for Ca homeostasis Thymus cytokines Immune regulation Heart both ventricles and atria secrete peptides that effect kidneys Liver transport hormones that help hydrophobic signals Insulin like growth factors Stomach peptides that regulate its own function Pancreas peptide hormones insulin glucagon etc Intestines secrete hormones that can target the pancreas or stomach Kidneys peptide and steroid hormones Adrenal gland adrenal medulla steroids amines The medulla develop from neurons but don t connect directly with axons o Cortex androgens glucocorticoids cortisol o Medulla NE E Skin steroid hormones Testes steroids and peptides Ovaries Adipose tissue peptide hormones that regulate metabolism and stimulate puberty Placenta steroids and peptides Neurotransmitter signaling very fast and has a high Km turnover rate is very high The NT receptor has low affinity with the NT that allows it to be controlled such that its present for only short amount of time It s very Endocrine signaling relies on the cardiovascular system so takes time to find the target organ The blood makes the signal diluted so receptors must have high affinity to the signal and low Km very generalized and not as Autocrine signaling when the ligand released comes back to regulated the specific specific organ itself Paracrine signaling affects only nearby cells because farther away the signal is too dilute to have an effect Ex prostaglandins Vasodilators constrictors Histamine released locally causes vasodilation K on H R HR K off K rate constants at which the reaction occurs K on Limited by diffusion and happens very fast K off is dependent on the association of the complex and at equilibrium H R HR k off k on K D equilibrium lies to the right if high affinity then low ligand is enough to make the complex and if have higher affinity then need less hormone to reach V max High K off and Affinity HR Low affinity and low K off H MM plot Scatchard plot linearize the MM plot with y axis as HR H and HR on the x page 6 Tyrosine derived amine hormones Tyrosine is a precursor for catecholamines and thyroid hormones Catecholamines DA NE Epi Made by a second hydroxylation of tyrosine o Ex dopamine normally inhibitory NT But as a hormone it s secreted by hypothalamus and inhibits secretion of prolactin o NE made from dopamine Sympathetic nerve terminals have enzymes that hydroxylates dopamine to make NE as a hormone secreted by adrenal medulla to increase sympathetic symptoms Adrenal medulla also secretes Epinephrine which is derived from NE Thyroid hormones synthesized on a protein that couple tyrosines and iodinates them Thyroxin 4 I T4 And Triiodothyronine T3 more active form of thyroid hormone Steroid hormones all derived from sterols Parent cholesterol compound In adrenal cortex Cortisol glucocorticoids Aldosterone mineralocorticoids Increase absorption of Ca in kidneys and increase excretion of potassium Estradiol an estrogens cholesterol under UV light can be made into Vitamin D which is a precursor for the active hormone that increases reabsorption of Ca in the kidneys and bone Its also important heart disease metabolism immunity and many other metabolic functions related to Ca Lipid messengers are mostly derived from Arachidonic Acid And are paracrine PLA 2 cleaves fatty acids to make arachidonic acid which serves as a precursor to many lipid soluble paracrines o Include thromboxanes and prostaglandins vasoconstriction dilation mucus fever o Aspirine and NSAID s inhibit prostaglandins to reduce the symptoms Cortisol also has a similar effect General Protein trafficking pre prohormone prohormone hormone Cytoplasm ER golgi The ss on the protein is recognized by SRP to pause the ER and then release the translated protein into the rough ER The rough ER translocates the preprohormone into the lumen and cleaves the ss to make the prohormone which is sent to the golgi via COPII vesicles Insulin precursor folded with disulfide bridges Proinsulin areas are8 cleaved to make active insulin and C peptide HR s 7TM receptors serpentine type with 7 hydrophobic domains The amino terminus is extracellular and the C terminus is intracellular Binds hydrophilic ligands All associated with G proteins so aka GPCR s also serve as NT receptors such as muscarinic Ach receptors and Alpha beta gamma subunit of G protein The subunit is photoreceptors phosphorylated R H G GDP R H G GTP GDP activated G protein diffuses to activate other enzymes in the membrane G alpha s AC cAMP PKA P ed various proteins either for a positive or inhibitory effect o cAMP binds to the regulatory subunit on the PKA causing it to dissociate off PKA to increase its activity The catalytic subunit of PKA can be transported into nucleus and P ate tf s G alpa i AC cAMP PKA G alpha q PLC beta IP3 DAG stays in membrane Ca PKC Ca to Cam CamK Turning signal off Remove the hormone to stop the signal from being cascaded G proteins also have enzymatic activity to hydrolyze GTP GDP to turn the protein off with the help of GAP cAMP can activate inhibitory proteins cAMP PDE that inactivate cAMP Cholera toxin inhibits G alpha s enzymatic activity so it is constitutively on This stimulates large amounts of adenylate cyclase In intestinal cells this leads to the opening of Cl channels which dehydrates the cells G alpha i the same sequence as G alpha s but it s inhibitory to AC Seen in intestinal and adrenergic cells alpha 2 G alpha q PLC beta head group PIP 2 on the PM PIP2 becomes IP3 8 9 12 Regulation of GPCRs Arrestin protein that blocks the receptor s interaction with G proteins Arrestin is activated from beta ARK from cAMP GRK needs to P ed the GPCR in order for arrestin to attach to the in the receptor receptors can also be endocytosed to decrease the cell s responsiveness to the ligand With a decreased number of receptors a higher number of desired ligand is needed to get the same effect seen in G alpha s Growth Factors ex Insulin GF I NGF EGF Use RTK s only have 1 TMD