Endocrine physiology
Terms
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- Definition of hormone
- bloodborne substance that regulates physiological process
- Functions of hormones
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1) digestion, utilization, storage of nutrients
2)growth and development
3)ion and water balance
4)reproductive function - Autocrine signaling
- acts on adjacent cells of same type or as negative feedback on same cell
- Paracrine signalling
- acts on adjacent target cells
- Endocrine signalling
- hormone secreted into blood and carried to target cells
- Neurocrine signalling
- released from neuron and diffuses into blood to target cells
- Amino acid derived and polypeptide/protein hormones
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-synthesized in advance and stored in vesicles
-may be cleaved from preprohormones or prohormones
-transported dissolved in plasma - Steroid hormones
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-cholesterol derivatives - hydrophobic
-produced on demand
-transported bound to plasma proteins - Hormone release characteristics
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-may be stimulated by NT --> higher brain areas stimulate hormone release in response to sensory input
-may be stimulated by another hormone --> hormone released into blood by one organ stimulates another to release a different hormone
-may be pulsatile --> pulse generator or circadian cycle stimulates hormone release in pulses in absense of external stimulation - Hormone transport
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Hydrophilic - dissolve easily in plasma - peptide hormones
Hydrophobic - bind to plasma proteins - steroid and thyroid, only free hormone binds receptor - Bound hormone is
- free hormone
- 2 types of hormone receptors
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-extracellular - peptide hormones that activate 2nd messenger systems
-intracellular - in cytoplasm, and hormone -receptor complex binds to DNA (steroid, thyroid, vitamin D, retinoic acid) - Down regulation occurs when
- there is chronically elevated hormone levels
- Up regulation occurs when
- chronically low hormone levels
- Describe hormone action pattern
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Follows dose-response curve
-basal activity intrinsic to cells
-threshold hormone concenration increases cellular response
-maximal response - no greater response can be elicited - ED 50
- Halfway between threshold and max response
- Hormone degradation mechanisms
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-by liver and kidney
-by target cells
-excreted in bile or urine - Half life of hormone
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time required to clear 50 % of hormone from blood
75 % in 2 half lifes, 87.5 in 3 - Feedback loops
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endocrine processes usually regulated by negative and rarely by positive feedback
This ensures maintenance of homeostasis - Hypothalamic derived hormones
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CRH - corticotropin releasing hormone
TRH - thyrotropin releasing hormone
GHRH - growth hormone releasing hormone
DA - dopamine
PRH - prolactin releasing hormone
Somatostatin - inhibits growth hormone and thyroid stimulating hormone secretion from pituitary
LHRH - lutenizing hormone releasing hormone - Posterior pituitary
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Axons from hypothalamus terminate on posterior pituitary
AP received at hypothalamus stimulates release into circulation - ADH action
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-stimulated by increased blood osmolality and decreased blood volume
-increases water reabsorption in collecting duct - Oxytocin action
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stimulated by breastfeeding and child birth
-increases milc secretion and uterine contractions - How oxytocin stimulates uterus
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-lowers threshold for smooth muscle depolarization
-causes rhythmic contractions - Anterior pituitary
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Hypothalamic hormones released into hypophyseal portal system
travel to pituitary and stimulate release of anterior pituitary hormones - DA inhibits which hormone
- Prolactin releasing hormone
- Anterior pituitary hormones
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ACTH - adrenocorticotropic - adrenals
TSH - thyroid stimulating - thyroid
GH - growth hormone - liver
FSH - ovaries and testes
LH - ovaries and testes
PRL - prolactin - breast - Adrenal cortex
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-Zona fasciculata + zona reticularis -stimulated by ACTH, secretes glucocorticoid and androgens
-Zona glomerulosa - secretes aldosterone - Aldosterone
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-stimulated by ACTH
-renin-angiotensin system primary stimulator - Androgens
- secreted by adrenal cortex in very low levels
- Thyroid gland
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-composed of follicular cells - filled with coloid, contain thyroglobulin, partially form T3 and T4 (iodines + tyrosine)
-parafollicular cells produce calcitonin, decreases Ca in blood - Thyroid hormone synthesis
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3 steps :
-throglobulin synthesis
-iodide uptake
-iodothyronine formation - Thyroglobulin synthesis and secretion
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-synthesized by ribosomes on rough ER
-undergoes dimerization and glycoylation in smooth ER
-packaged into vesicles by Golgi
-extruded into colloid - Iodide uptake
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-follicular iodide transporters carry iodide into cell (ATP driven, iodide trapping)
-iodide diffuses into colloid for iodination - Formation of iodothyronine
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-thyroid peroxidase catalyzes iodination
-binds iodide ion and tyrosine in thyroglobulin
-undergoes oxidation
-produces monoiodotyrosine (MIT)
-MIT undergoes iodination to DIT
-MIT and DIT remain connected to thyroglobulin - Thyroid hormone formation
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Colloid droplets are exocytosed
-lysosomes migrate towards droplets, fuse with them, and hydrolyze thyroglobulin - T3 and T4 released in cytosol and diffuse to blood - Thyroid hormone action at target
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T4 and T3 diffuse into cell, T4 converted to T3
-intracellular receptors similar to steroid receptors
-gene expression altered
-influences CNS development, growth and metabolism - Hypersecretion of thyroid hormone
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-Excitability
-Excessive sweating
-Weight loss but increased food intake
-diarrhea
-fatigue but inability to sleep
-muscle weakness
-tremor
-protruding eyes - Hyposecretion of thyroid hormone
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-obesity but reduced appetite
-excessive sleeping
-mental sluggishness
-constipation
-lower body temperature - Growth hormone actions
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One of counter regulatory hormones, limit actions of insulin on liver, adipose and muscle
-inhibits glucose use by muscle and adipose
-increases gluconeogenesis
-makes muscle and adipose resistant to insulin - Pituitary dwarfism
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-may be due to lack of GH only or GH and other pituitary hormones
-may be due to dysfunctional receptor - GH excess leads to what
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-gigantism - can grow to 7-8 ft tall
-excess occuring in adulthood causes bones of hands, feet, face to thicken and organ hypertrophy - acromegaly
-metabolic disturbances - insulin resistance, hyperglycemia - Insulin dependent glucose transport
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-tissues requiing insulin for efficient glucose transport are adipose and resting skeletal muscle
-insulin facilitaties glucose uptake in liver - enhances glucose metabolism, does not insert glucose transporters here - DM general symptoms
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-frequent urination
-increased thirst
-increased food consumption
-weight loss - Type I diabetes
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-inadequate insulin production - mutation in insulin gene, autoimmune disorder and some environmental factors
-Insulin injections REQUIRED - Type II diabetes
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Causes :
-insulin resistance at target tissues
normal to high insulin levels in blood
may be receptor or post receptor defect
-Strong genetic component
-diet plays big role
-being overweight increases risk - Treatments for type II diabetes
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-milder forms - diet and exercise
-sulfonylurea drugs - increase insulin action and production
-some cases insulin treatment necessary - Parathyroid hormone
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-main action on renal tubule and bone
-increased Ca reabsorption and decreased phosphate reabsorption
-increased bone resorption - Vitamin D
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main action on intestine and bone
-increases intestinal Ca and P absorption
-increase bone formation and resorption
-small increase in renal Ca reabsorption - Calcitonin
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Main action on bone
Deactivates osteoclasts to decrease bone resorption