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BIOL 245 Endocrine System 1 I. Hormones A. From endocrine glands B. Target tissues C. Classes 1. protein based a. glycoproteins: b. polypeptides 2. biogenic amines (monoamines) - amino acid-based: - tyrosine derived: 3. steroids (cholesterol-based) a. cortisol b. sex steroids D. Synthesis and transport 1. steroids a. bound to hydrophilic transport proteins b. unbound form taken up by target cells 2. thyroid - thyroxine-binding globulin (TBG) E. Inactive forms (long) 1. preprohormone --> prohormones --> active hormone - preproinsulin ---> proinsulin ---> insulin 2. some forms not activated until inside target cells F. Requirements for proper activity 1. receptors on/in target cells 2. binding of hormone to receptor causes change in the activity of target cell G. Interactions 1. synergistic a. additive or complementary b. examples: 2. permissive: enhances effect of another hormone a. ↑ responsiveness of target organ to another hormone b. ↑ activity of another hormone 3. antagonistic a. lactation (via prolactin) inhibited by ↑ E2 b. insulin vs. glucagon II. Mechanisms of Hormone Action A. Interaction with receptors on/in target cells 1. high specificity 2. high affinity 3. low capacity 4. types of interactions vary depending on hormone class a. nuclear receptors: b. cytoplasmic receptors: c. membrane receptors: B. Steroid/Thyroid mechanisms 1. each type is nonpolar 2. transported by plasma carrier proteins 3. nuclear: (steroids) a. binding of hormone changes conformation of receptor b. hormone-receptor complex binds to acceptor sites (usually on DNA) c. activates gene transcription 4. thyroxine a. only about 0.04% of T4 is “free” in plasma b. converted to T3 in cell (small amount of free T3 in plasma) c. T3 receptor is bound to chromatin C. Second-messenger activation 1. hormone is first messenger 2. cAMP a. catechols and some protein-derived b. ATP ---> cAMP c. cAMP activates protein kinases ----> protein phosphorylation 3. Ca++ a. intracellular [Ca++] normally very low b. example: α-adrenergic stimulation via epi - activates phospholipase (enzyme) - phospholipase breaks down phospholipids ---> IP3 - IP3 triggers ↑ in intracellular [Ca++] - Ca++ binds to and activates calmodulin - activation of protein kinases D. Receptor regulation - up or down-regulation