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Endocrine System |
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-Endocrine glands (ductless) secrete hormones
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Hormones |
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intercellular chemical messengers that are secreted into the blood and each target cells thru circulation |
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Chemical classes of hormones |
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1. Amines
2. Proteins and Peptides
3. Steroids |
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Amines |
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-derivative of tyrosine
* Thyroid Hormones
-T3 and T4 (secretes more T4, but T3 has higher activity)
* Catecholamines
-Norepinephrine, Epinephrine, and Dopamine |
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Thyroid Gland |
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-anterior neck
-circular arrangement of epithelial cells surround thyroid follicle; no blood within follicle |
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Synthesis of T3 and T4 in Thyroid Gland |
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-Uptake of I- from blood and transport thru epithelial cells of thyroid follicles into follicular lumen
-Secretion of Thyroglobulin into follicular lumen
-Oxidation of I- to I and incorporation into thyroid hormone molecules that are part of Thyroglobulin |
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Storage of T3 and T4 in Thyroid Gland |
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-Thyroglobulin is the colloid in follicular lumen
-Thyrogloblin = storage form of T3 and T4 |
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Release of T3 and T4 from Thyroid Gland |
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-Endocytosis of thyroglobulin by thyroid follicular cells
-Intracellular hydrolysis of thyroglobulin, which yields 3 thyroid hormone molecules
-Release of T4 and T3 into blood (most is T4) |
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Transport of T4 and T3 in Blood |
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-Binding to thyroxine-binding globulin (TBG)
-Most T3 and T4 in blood are in bound form
-Only free form is active (can be taken into target)
*T3 and T4 - nonpolar so can bind to TBG
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Intracellular Actions of T4 and T3 in Target Cells |
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-Carrier-mediated uptake of T3 and T4 into target cells
-T4 converted to T3 by intracellular deiodinase
-T3 enters nucleus and binds to thyroid hormone receptors
-Hormone-receptor complex acts as transcription factor |
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Actions of Thyroid Hormone on Target Tissues |
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-Target tissues = all tissues in body, except RBCs (no nucleus)
Actions:
- stimulation of MR (calorigenic effect) -increased activity of Na/K-ATPase
-Permissive for catecholamine effects (permissive = presence of one hormone is necessary for action of another)- upregulation of beta adrenergic receptors
-Tissue growth- synthesis and growth-promoting actions of growth hormone from ant pit.
-Nervous system development and function- fetal brain dev and postnatal nervous system func (reflex, cognition) |
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Symptoms of Hypothyroidism |
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-Low BMR
-Cold intolerance
-Weight gain
-Lethargy
-Slow reflexes |
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Symptoms of Hyperthyroidism |
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-High BMR
-Heat intolerance
-Weight loss
-Hyperactivity
-Rapid reflexes |
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Catecholamines |
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Sources:
Adrenal medulla- norepinephrine (20%) and epinephrine (80%)
Hypothalamus- dopamine
-Transported thru circulation w/o binding protein - very water soluble |
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Catecholamine Receptors |
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Types:
-Adrenergic- NE and Epi
-Dopaminergic- Dop
Location: plasma membrane
Receptors: act as ion channels, enzymes, or allosteric activation of G proteins |
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Actions of NE and Epi |
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Heart: stim HR and force of contraction (CO, BP)
Vascular smooth muscle: stimulates contraction and/or relaxation (BP)
Liver and skeletal muscle: carb metabolism (stim glycogenolysis and gluconeogenesis (blood glucose))
Adipose tissue: fat metabolism (stim lipolysis (energy, blood glucose))
Pancreatic islets: hormone secretion (inhibit insulin sec, stim glucagon secretion) |
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Actions of Dopamine |
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Ant Pit Gland: inhibits prolaction secretion |
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Snthesis of proteins |
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Preprohormone
Prohormone
Hormone
Hormone |
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Protein/Peptide hormones |
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-Most hormones
-Hypothalamus: most
-Post and Ant Pit: all
-GI system: all
-Pancreas: important ones for metabolism |
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Protein/Peptide Receptors |
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-Many types
-Location: plasma membranes (polar)
-Receptors: act as ion channels, enzymes, or allosteric activation of G proteins |
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Steroid Hormones |
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-derived from cholesterol
-highly nonpolar --> not stored |
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Adrenal Gland |
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Medulla = inner
Cortex = outer
1. Zona Glomerulosa- aldosterone
2. Zona Fasiculata- cortisol, androgens
3. Zona Reticularis- Epi and NE |
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Major Steroid Hormones of Adrenal Cortex |
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1. Corticosterone
2. Aldosterone
3. Cholesterol
4. Cortisol
5. Androgens = Dehydroepiandrosterone and Androsternedione |
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Types of Adrenocortical Steroids |
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1. Mineralcorticoids
-Actions on renal handling of minerals (Na and K)
-Aldosterone and Corticosterone
2. Glucocorticoids
-Actions on carb metabolism
-Actions in stress responses
-Cortisol and Corticosterone
3. Androgens
-Actions similar to those of testosterone, but weaker
-Dehydroepiandrosterone (DHEA)
-Androstenedione (ASD) |
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Transport of Adrenal Corticosteroids in Blood |
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-Binding to corticosteroid binding globulin (CBG)
-Most in blood are bound
-Only free form are active |
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Intracellular Actions of Adrenal Corticosteroids in Target Cells |
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-Diffuse into target cells
-Receptors for corticosteroids are intracellular
-Hormone-receptor complexes act as transcription factors |
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Actions of Normal Basal Concentrations of Cortisol on Target Tissues |
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-Permissive for catecholamine actions on vascular smooth muscle (bp)
-Permissive for enzyme levels that mediate gluconeogenesis (liver) and lipolysis (adipose)
-Permissive for normal fetal and neonatal dev |
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Actions of Stress Levels (Inc conc) of Cortisol on Target Tissues |
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-Enhanced vascular reactivity to catecholamines (bp)
-Enhanced actions on metabolism to provide extra fuel sources and to maintain blood glucose:
inc. protein catabolism. gluconeogensis, lipolysis
dec. glucose uptake by skeletal muscle and adipose tissue |
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Gonadal Steroid Hormones |
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Males:
Androgens
Testosterone
Females:
Estrogens
Estradiol
Progesterone
*estrogen is generic term that included estrone, estradiol, etic. |
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Males |
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Testes = testosterone |
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Female |
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Ovaries = predominant steroid varies w/ phase of menstrual cycle
Follicular phase (1st 2 wks) = Estradiol
Luteal phase (2nd 2 wks) = Progesterone |
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Transport of Gondal Steroids in Blood |
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-Binding to sex hormone binding globulin (SHBG)
-Most are bound form
-Free form is active |
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Intracellular Actions of Gonadal Steroids on Target Tissues |
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-Diffuse into target cells
-Location = intracellular
-Hormone-receptor complexes act as transcription factors |
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Conversion of Gonadal Steroids to Active Forms in Some Target Cells in Male |
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Testosterone -> 5-alpha-Dihydrotestosterone
Testosterone -> Estradiol |
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Mechanism of Action of Hormones with Intracelullular Receptors |
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-Free hormone diffuses through cell (nonpolar)
-Receptors in nucleus
-Function as transcription factor |
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Mechanism of Action of Hormones with Plasma Membrane Receptors |
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-Polar
-Receptors on plasma membranes |
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Regulation of Hormone Receptors |
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-By natural hormonal ligands: up and down reg
-By other hormones: permissive effects, whereby presence of one hormone is necessary for action of another hormone |
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Permissive Action of Thyroid Hormone on Epinephrine-Induced Lipolysis |
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Thyroid hormone = little effect
Epinephrine = min effect
TH and Epi = large effect |
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