Beruflich Dokumente
Kultur Dokumente
Mariusz Mydlarczyk
Hormones
Substances, that are secreted into the circulation and act as chemical effectors in other tissues
Chemistry of hormones
Peptides
Small peptides Polypeptides Glycopeptides
Submits:
derived from single precursor derived from separate precursors
The same peptide cam be formed from different prohormone encoded by distinct genes (TSH) Individual prohormone can be metabolized into different hormones (POMC)
Release mechanisms
Conversion of insoluble to soluble derivatives (proteolysis of thyroglobulin) Exocytosis of storage granules (insulin, glucagon, prolactin, GH) Passive diffusion of newly synthesized molecules (steroids)
Pulsatile administration of LHRH stimulates the release of LH by the pituitary, whereas the constant infusion of the same amount of hormone per unit time has the opposite effects
Transport of Hormones
Blood Lymph Extracellular fluid
Total hormone
Free fraction
Degradation of hormones
Small fraction is excreted intact in urine or bile (free hormones) Degradation takes place in:
target tissues (peptide hormones) nontarget tissues (liver, kidneys)
Hormone receptors
Cell surface receptors Intracellular receptors
Cytoplasmatic Nuclear Mitochondrial
Hormone
G protein
Binding domain Class II of protein receptor Tyrosine kinase domain Binding domain Class III of protein receptor Accessory protein with tyrosine kinase domain
Nuclear receptors
Nuclear receptors are ligand-regulated transcription factor that control gene expression by binding to target genes usually in the region near their promoters. Class I: steroid hormone. Unliganted receptors are associated with heat shock proteins and are present in either the cytosol or the nucleus. Ligand binding promotes dissociation of the heat shock proteins and formation of receptor homodimers that bind to specific DNA elements (HREs hormone response elements) Class II: thyroid hormone, retinoid, vitamin D, peroxisimal proliferator-activated receptors (PPR). Receptors already present in the nucleus in the uliganted state. They are commonly active in the absence of hormone
Classification of ligands
Inactive compounds Agonists Antagonists Partial agonist, partial antagonists Mixed agonists-antagonists
Hormone Receptor (Beta adrenergic, D1, V2, H2, GHRH, glucagon, TSH, ACTH, FSH, LH) GTP Gs protein Adenylyl cyclase ATP Protein kinases A (PKA) Protein phosphorylation Phosphoprotein phosphatases (PP) Biological effects cAMP GDP
Hormone Receptor (Alpha2 adrenergic, D2) GTP Gi protein Adenylyl cyclase ATP Protein kinases A (PKA) Protein phosphorylation Phosphoprotein phosphatases (PP) Biological effects cAMP GDP
Hormone Receptor (ANP) Guanylyl cyclase GTP Protein kinases G (PKG) Protein phosphorylation Phosphoprotein phosphatases (PP) Biological effects cGMP
Hormone Receptor (alpha1 adrenergic, H1, GnRH, TRH, V1, AT1) GTP Gq protein Phospholipase C (PLC) Phosphatidylinositol Inositoltriphosphate (IP3) Ca++ Phospholipase A2 (PLA2) Arachidonic acid cascade Diacylglycerol (DAG) Protein kinases C (PKC) Protein phosphorylation Protein dephosphorylation Phosphoprotein phosphatases (PP) GDP
Calmoduline
Arachidonic acid cascade Cell membrane phospholypides Phospholipase A2 Arachidonic acid (AA) Cyclooxygenase PGG2 PGH2 PGs TxA2 PGI2 Lipooxygenase 5HPETE LTX
Hypothalamus
(-)
(-)
Target hormone
(+)
Endocrine hypofunction
Destruction of gland: autoimmune disease, neoplasm, infection, hemorrhage, injury The absence of stimulation by trophic hormone Defects in hormone synthesis Defects in sensitivity to hormones Damage to tissues that produce active forms of hormones Increased hormone metabolism
Endocrine hyperfunction
Tumors Ectopic production of peptide hormones Hyperplasia Autoimmune stimulation Stimulation by trophic hormone Diminished hormone metabolism
Hypofunction
Destruction Block Block Stimulation Degraded Antibodies Defect Receptor Effector Response Hormone Gland Prohormone
Hyperfunction
Tumor Hyperplasia Ectopic production Iatrogenic Block Degraded Antibodies Stimulation
Hypothalamus
Portal pituitary circulation
Hypothalamus Portal pituitary circulation Anterior pituitary lobe Trophic hormone Target endocrine organ Target hormone
Hypothalamus Portal pituitary circulation Anterior pituitary lobe Trophic hormone Target hormone
Hypothalamus
Portal pituitary circulation
Target hormone
Hormonal resistance
Hypothalamus
Portal pituitary circulation
Normal Low
Secondary target endocrine organ failure
Low
High