ERMNotes - Transport Protein Receptor Type Example...

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Endocrine Basics Major Functions of the Endocrine System Reproduction Growth and Development Energy production, utilization, and storage Immunity Homeostasis Endocrine Paracrine Autocrine Intracrine Molecule enters circulation and acts on a distant target cell Molecule acts on neighboring cell Molecule acts on receptors from the cell that produced it Intracellular signaling molecules Growth hormone Retinoic acid Insulin-like growth factor Oxysterol Hormone Type Transport Protein Water-soluble None Water-insoluble General (e.g. albumin) Specific (e.g. thyroxine- binding globullin) edback xample Receptor Type Example Mechanism Tyrosine Kinases Insulin IGF-1 Ligand binding induces autophosphorylation, which generates docking sites for intracellular signal transduction molecules (e.g. IRS and Shc) that lead to signaling cascades. Kinase-linked Growth hormone Leptin Ligand binding causes activation of downstream kinases. G-Protein- Linked cAMP/PKA (ACTH, LH) Ca 2+ /PKC (GnRH, PGF2a) Ligand binding causes activation of heterotrimeric G proteins, which dissociate and lead to downstream transcriptional and nontranscriptional events. Steroid Hormone Receptor Steroid hormone receptors are bound to heat shock protein complexes, which prevent them from binding DNA. Ligand binding allows dissociation from HSPC and binding to the hormone response element to regulate responses of target genes. Heterodimeric Nuclear Interaction with the Retinoid X Receptor allows DNA binding with some basal transcriptional effect. Ligand binding switches state of activity from off to on by recruiting co-activator complexes. Monomeric Nuclear Receptors are not activated by ligands, but by other signals like phosphorylation Location Factors Affecting Hormone Activity Hormone Activity Endocrine Hormone deficiency due to: Molecule Indications Thyroid Hormone (HRT) Hypothyroidism Peptide and Amino Acid Derived Complex polypeptides Intermediate-sized polypeptides Small peptides Dipeptides Amino acid derivatives Non-Peptide, Steroid Androgen Estrogen Glucocorticoid Mineralocorticoid Progestin Non-Peptide, Non-Steroid Vitamin D Retinoids Fatty acid derivatives Feedback Example Negative feedback Anterior pituitary makes TSH, which regulates thyroid production of thyroid hormone. Thyroid hormone suppresses anterior pituitary gland. Positive feedback Ovary produces estradiol, which stimulates the hypothalamus to release LH. LH increases ovarian production of estradiol. Product regulation Parathyroid gland makes PTH, which acts to increase bone resorption and liberate calcium. Serum calcium suppresses PTH production by the parathyroid gland. cell 1. Gland defect 2. Gland destruction Hormone excess due to: 1. Hyperplasia 2. Tumor Blood Vessel Increased hormone-binding protein Reduced hormone-binding protein Target Cell Tissue resistance due to: 1. Receptor defect 2. Receptor signaling defect Excessive response due to: 1. Activating receptor mutation Estrogens, Progestins, Androgens (HRT)
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ERMNotes - Transport Protein Receptor Type Example...

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