Ch1 introduction

• The endocrine system connects the brain and the body.
• In the brain, neurons signal to each other by releasing neurotransmitters and neuromodulators across synaptic cleft, which is a local signal.
• Endocrine and neuroendocrine cells release hormones into bloodstream or body fluids, which is a regional or global signal.
• Molecular mechanisms of bioregulators are similar and sometimes involve identical molecules and receptors.
• Water-soluble hormones/transmitters include amino acids, amines, peptides, and proteins, which act mostly through transmembrane receptors.
• Lipid-soluble hormones/factors include steroids, eicosanoids, retinoids, and thyroid hormones, which act mostly through nuclear receptors.
• There are different types of bioregulators.
• Gq activates phospholipase C, leading to the synthesis of IP3 and DAG.
• Associates with plasma membrane through lipid tail of γ subunit.
• Receptor stimulation dissociates α from β + γ; α exchanges GTP for GDP.
• Stimulatory and inhibitory G proteins (Gs & Gi) include forskolin, pertussis toxin, and cholera toxin.
• Phosphorylation of the receptor inactivates the receptor, even if the ligand is bound.
• Degradation of 2nd messengers cAMP and calcium have short half-lives and require continuous production.
• Activated α interacts with downstream effectors: Gq stimulates phospholipase C, Gs stimulates adenylyl cyclase, Gi inhibits adenylyl cyclase.
• α and β adrenergic receptors activate different G proteins, leading to different responses.
• The gain of the hormonal signal can be regulated through the process of endocytosis, where fewer receptors are present at the cell surface.
• Receptor downregulation and recycling are important processes in the regulation of G protein-coupled receptors.
• Removal of the extracellular ligand terminates the signal.
• Steroids have a complex ring structure with 27 carbon atoms, while other lipid hormones have 18, 19, or 21 carbon atoms.
• Lipid bioregulators are fat-soluble and can cross the plasma membrane to bind nuclear receptors that shuttle between the cytoplasm and nucleus.
• Steroids use different plasma-binding proteins, including corticosteroid binding globulin and sex hormone binding globulin.
• Vitamin D (calcitriol) is a secosteroid derived from cholesterol, synthesized or taken up in diet, and its conversion to vitamin D3 in skin involves UV light.
• Prostaglandins are involved in pain and fever.
• Steroid synthesis involves the conversion of cholesterol to various steroids, which can be obtained from diet or synthesized endogenously from mevalonate.
• Steroids and other lipid hormones are synthesized in the mitochondria and smooth endoplasmic reticulum (SER) and produced enzymatically from acetyl-CoA.
• Lipid bioregulators are usually not stored in endomembrane vesicles and are produced de novo, except for thyroid hormones which are a special case.
• Retinoic acid is an isoprenoid derived from vitamin A, produced in plants from farnesyl pyrophosphate, the same precursor as steroids, and converted to retinoic acid in animal cells.
• The rate of production controls the rate of release for lipid hormones.
• Eicosanoids are lipid hormones derived from arachidonic acid, a fatty acid, and there are diverse families of eicosanoid molecules involved in inflammatory responses, clotting, modulation of muscle and neurons.
• Melatonin is a pineal neurohormone, secreted primarily in the dark and important in the regulation of biorhythms
• Serotonin or 5 - hydroxytryptamine is a neurotransmitter in the brain (Raphe nuclei)
• Amines are stored in vesicles, loaded by vesicular transporter, and released by calcium-triggered exocytosis.
• Peptide hormones are synthesized in the endoplasmic reticulum, packaged into secretory vesicles, and released into the bloodstream through exocytosis.
• Amines, peptides and proteins: synthesis and release
• Peripheral catecholamines are metabolized by liver monoamine oxidase
• Trace amines (including tyramine) play less defined roles in mammals; important in invertebrates
• Glycoprotein hormones LH, FSH and TSH each have unique β subunits and α subunits.
• Dopamine, norepinephrine & epinephrine are neurotransmitters as well as (neuro)hormones
• Serotonin is also released from enterochromaffin (EC) cells to control gut motility and secretion (90% of all serotonin in human)
• Synthesis & action of bioregulators 4