Growth hormone replacement therapy in elderly growth hormone ...
Hormone actions
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Transcript of Hormone actions
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Hormone actions
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Hormones
• Three subgroups based on chemical nature– Proteins– Lipids
• Cholesterol • Eicosanoids
– Animo acid derivatives
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Hormones
• Biological activities– Mediated by the receptor
• Receptors– Protein
• Interacts with specific hormone• Diverse
– Membrane-bound– Intracellular/nuclear
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• Interactions between hormone and receptor– Very specific– Depending upon the structural conformation
• 3-D structure• Chemical structure
– Side-chains
– Rings
– Some receptors bind to more than one hormone• Glucocorticoids bind to progesterone receptor and vise varsa• Effectiveness differ based on what hormone is bound to the
receptor
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• Interaction of hormone with its receptor– Natural hormone– Synthetic hormone (same chemical
composition and structure)• Analogues
– Synthetic hormone that elicit greater response• Agonist
– Synthetic hormone that prevents response• Antagonits
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Regulation of hormone activity
• Factors– Amount of hormones available
• Free form• Available to interact with receptor
– Amount of receptors present• Production
– Transcription of mRNA for the receptor– Translation of mRNA for the receptor
• Occupancy of the receptor
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• Factors– Rate of clearance
• Circulation• Receptor turn-over
– Removal/recycling of receptor after the hormone binds
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Transduction of hormonal signals
• Interaction of hormone with its receptor– Generation of intracellular signals– Different among different hormones
• Production of chemicals within the cell– Secondary messenger
• Interaction with DNA– Nuclear receptors
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• Protein hormones– Alteration of
intracellular chemistry• Changes in
concentrations of biochemical molecules
– Alteration of biochemical molecule activity
• Activation/inhibition of intracellular proteins
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Types of intracellular signaling
• Types of receptor– G-protein coupled receptors (very common)
• Seven trasmembrane domain receptor• Intracellular proteins (G-proteins)
– Activated by attachment of GTP to one of the G-proteins– Activated G-protein in turn activates other intracellular
proteins
– Secondary messenger• Cyclic AMP (cAMP)• Phosphatidyl inositol and Ca ions
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• Types of receptor– Proteins with intrinsic kinase activity
• Attach phosphate ions to itself (tyrosine residue)• Activation of other intracellular proteins through
phosphorylation
– Proteins that have intracellular kinase associated• Binding of hormone results in phosphorylation of associated
kinase rather than the receptor protein itself
– Results of receptor activation• Activation of transcription• Often affects metabolism and growth of cell
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• Nuclear hormone receptors– Steroid hormone receptors
• Two domains– Ligand binding domain (binds hormone)– DNA binding domain
• Require dimerization– Two receptors interact with each other– Homodimer or hetelodimer
• Interacts with DNA– Hormone responsive element– Triggers transcription of hormone-responsive genes
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Hormone concentrations in blood
• Fluctuation in blood concentrations of hormone– Secretion pattern
• Variation throughout the day• Rhythmic pattern
– Circadian rhythm
• Pulse-like pattern• Surge-like pattern
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• Availability of hormone to the receptor– Free form
• Hormone itself
– Bound form• Hormone plus other blood protein(s) that binds to
hormone– Sex hormone-binding globulin (SHBG)– Insulin-like growth factor-binding proteins (IGFBPs)
• Regulation of free form being available for action
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• Metabolism of hormone– Cleared as it goes through the circulation
• Liver• Lungs
– Cleared at the site of action• Receptor internalization• Metabolic clearance
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Neural control of reproduction
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Reproductive organs
• Development and function– Regulated by hormones
• Gonadotropins• Steroids• Prostaglandins• Growth factors
• Production of hormones– Control of the central nervous system
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Neural control
• Hypothalamus– “Old” part of brain (primitive brain)– Involved in homeostasis of internal
environment• Sensory information from external environment• Generation of appropriate response
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Anatomy of hypothalamus
• Landmarks– Anterior (front)
• Optic chiasm (crossing of optic nerve fibers)
– Posterior (dorsal/back)• Mamillary body
– Superior (cranial)• Third ventricle
– Inferior• Pituitary
stalk/infundiblum
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• Neural organization of hypothalamus– Clusters of neurons
• Nucleus/nuclei
– Different section of hypothalamus contains different nuclei
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• Regional distribution of nuclei– Supraoptic – Paraventricular – Arcuate– Ventromedial– Suprachiasmatic– Medial anterior
hypothalamic– Medial preoptic area
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Hypothalamic control of hormone production
• Neural connection to the pituitary gland– Posterior pituitary gland (neurohypophysis)
• Neural cells that produce oxytocin and vasopression are located in the hypothalamus
• Hormones transported to the posterior pitutiary gland via axoplasmic flow
– Axons of neurons extended into the posterior pituitary gland
– Magnocellular neurosecretory system
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Hypothalamic control of hormone production
• Circulatory connection to the pituitary gland– Anterior pituitary gland (adenohypophysis)
• Neural cells that produce releasing factors are located in the hypothalamus
– Axons terminate in primary portal plexus of capillaries located in the median eminence
– Parvocellular neurosecretory system
• Hormones transported to the anterior pitutiary gland via portal vessels
– Microcirculation between the hypothalamus and anterior pituitary gland
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Gonadotropin-releasing hormone (GnRH)
• Hypothalamic neuropeptide– 10 amino acids– Produced by the neurons
• Caudal medial septal nucleus• Paraventricular medial preoptic area
– Released into the circulation via lateral parisade zone of the portal plexus
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Gonadotropin-releasing hormone (GnRH)
• Crucial hormone for regulation of gonadal function– Controls release of gonadotropins (LH and
FSH)– Pattern of release is reflected in pattern of
blood gonadotropin concentrations• Pulsatile• Surge-like
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• Pulsatile secretion of GnRH– Critical for function of gonads
• Pulsatile secretion of LH and FSH
– Pulse generator• Neurons in median eminence• Circhoral clock