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Target Tissue Specificity and Response
Hormones exert actions by binding to proteins called receptors and can only stimualte cells that have the receptor for that hormone (receptor site) - creates specificity; only small concentraion of given hormone is needed to activate a significant # of its receptors due to a high affinity for the hormones that bind to them
Regulation of Receptor Numbers
target tissues' sensitivity to hormone levels can change; changing the receptor number at target ensures an optimal target tissue response to hormone; Down-regulation and Up-regulation
Decrease in Receptor Numbers
the response of some target tissues rapidly decrases through time through desensitization; this happens because cells' nutrient and energy supplies become depleted, causing cells to lose the ability to respond to hormone; Down regulation of hormones
Down-Regulation of Receptor Numbers
desensitization occurs when the number of receptors rapidly decreases after exposure to certain hormones; often, target cells internalize the receptors and destroy them
Up-Regulation of Receptor Numbers
increase in sensitivity of hormone; results from increase in rate of receptor molecule synthesis in target cells; a tissues exposure to one hormone can increase sensitivity to a second hormone; ex - increased # of receptors for LH in ovary cells during menstrual cycle, FSH secreated by pituitary increases rate of LH recetor cynthesis in ovary cells to release egg. T3 also another example
Nuclear Receptors (Lipid Soluble)
hormones are lipid soluble and relatively small molecules; pass through plasma membrane; react either with enzymes in cytoplasm (and move to nucleus) or with DNA (in nucleus) to cause transcription and translation; Ex - steroids (testosterone, estrogen, progesterone, aldosterone), cortisol
Membrane Bound Receptors (Water Soluble)
integral proteins with receptor site at extracellular surfgace; interact with hormones that cannot pass through plasma membrane; Hormones are water soluble or large molecular weight, attachment causes intracellular reaction; Ex - large proteins, glycoproteins, polypeptides, smaller molecules like epinephrine and norepinephrine
Nuclear Receptor Actions
proteins are in cytoplasm or nucleus; hormones bind with intracelluar receptor and receptor-hormone complex activates certain genes, causes transcription of mRNA and translation which make a protein; these proteins (enzymes) produce the response of the target cell to the hormone; process limited by breakdown of receptor-hormone complex
How long does it take for a Nuclear Receptor to take effect?
latent period of several hours because time is required to produce mRNA and protein (enzyme)
Nuclear Receptor Examples
Estrogen and testosterone produce different proteins in cells that cause the differing secondary sexual characteristics of females and males; Aldosteron (steroid hormone) affects target cell sin kidneys by stimulating synthesis of proteins that increase the rate of Na+ & K+ transport,resulting in reduction of of Na+ & increase of K+ lost in urine
have peptide chains that are anchored in lipid bilayer of plasma membrane for transport of water soluble or large molecules; regulate intracellular enzyme activities
2 Ways Membrane-Bound Receptors Active Responses
1) directly alter activity of intracellular enzymes; these intracellular pathways elicit specific responses in cells, including intracellular mediators; 2) alter activity of G proteins at inner surface of plasma membrane
Intracellular Mediators of Membrane-Bound Receptors
ions or molecules (chemical) that enter cell or are produced in cell once a hormone or another chemical messenger binds to certain membrane-bound receptors; some are called second messengers
Secondary-Messenger System of Membrane-Bound Receptors
intracellular mediator activates specific ellular processes inside cell in response to hormone or other chemical messenger that binds to membrane-bound receptors
Receptors that Directly Alter Activity of Intracellular Enzymes
some hormones bind to membrane bound receptors (MBR) and directly change activity of intracellular enzymes (IE); altered enzyme activity regulates synthesis of intracellular mediators (IM) or result in phosphorylation of intracellular proteins which activate processes that produce cell's response to chemical signals; IE's can be controlled by MBR or can be separate molecules; IM act as chem signal to move from enzymes that produce them into cytoplasm of cell, where they activate processes that produce cells response; EX - hormone glucagon activates enzymes that release glucose into circulation from liver cells
Receptors that Directly Activate Intracellular Mediators
Cyclic guanine monophosphate (cGMP-intracellular mediator), is synthesized in response to hormone binding to membrane bound receptor; hormone binds to receptor and combo activates enzyme guanylate cyclase (GC) located at inner surface plasma membrane; GC converts GTP to cGMP and 2 inorganic phosphate groups; cGMP combines with specific enzymes to activate and cause cell's response
Receptors and Intracellular Mediator Example
atrial natriuretic hormone (secreted by heart atria) binds with receptor in plasma memb of kindey cells; result is increase rate of cGMP synthesis at inner surface of PM; cGMP influences action of enzymes in kidney cells, which increase kidneys' rate of Na+ and water exretion; cGMP is present in cell for only liped amount of time because phosphodiesterase brakes down cGMP to GMP
Receptors that Phosphorylate Intracellular Proteins
hormone binds to mem-bound receptor, inner portion acts as a kinase enzyme that phosphorylates several specific proteins; some are part of mem-bound receptor, others are in cytoplasm; phosphorylated proteins influence activity of other enzymes in cytoplasm
Receptors and Phosphoryaltion Example
insulin binds to its mem-bound receptor, resulting of phospho. of parts of receptor on inner surface of PM and phospho of certain other intracellular proteins; phosphorylated proteins enable the very powerful effects of insulin to allow glucose entry into cells
Hormones that stimulate synthesis of second messengers can produce an almost instananeous response becuase they influence existing enzymes;each receptor produces thousands of second messengers, leading to a cascade effect and ultimately amplification of hormonal signal
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