8/7/12- Survey of Hormones:Pineal Gland: melatonin secretion. In response to darkness to reset biological clock. Melatonin=amineHypothalamus: cluster of neurons. Peptide hormones. Vasopressin/ADH and oxytocin.Pituitary gland: posterior: extensions of the hypothalamic neuronsAnterior: 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 aminesParathyroid: produce PH essential for Ca homeostasis.Thymus: cytokines. Immune regulationHeart: both ventricles and atria secrete peptides that effect kidneys.Liver: transport hormones that help hydrophobic signals. Insulin like growth factorsStomach: peptides that regulate its own functionPancreas: peptide hormones, insulin, glucagon etc.Intestines: secrete hormones that can target the pancreas or stomach.Kidneys: peptide and steroid hormonesAdrenal gland/adrenal medulla: steroids/amines. The medulla develop from neurons but don’t connect directly with axons.Cortex: androgens, glucocorticoids, cortisol.Medulla: NE/ESkin: steroid hormonesTestes: steroids and peptidesOvaries: “”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 specific.-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 specific.- Autocrine signaling: when the ligand released comes back to regulated the 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 fastK_off is dependent on the association of the complex and at equilibrium([H][R])/[HR]=k_off/k_on= K_D- if high affinity, then low [ligand] is enough to make the complex and equilibrium lies to the right.- 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 hormonesCatecholamines: DA, NE/Epi. Made by a second hydroxylation of tyrosine.Ex. dopamine: normally inhibitory NT. But as a hormone, it’s secreted by hypothalamus and inhibits secretion of prolactin.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: glucocorticoidsAldosterone: 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.Include thromboxanes and prostaglandins (vasoconstriction/dilation, mucus, fever).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’salso serve as NT receptors such as muscarinic Ach receptors and photoreceptors.Alpha/beta/gamma subunit: of G protein. The subunit is 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)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 -PKAG_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