Endocrine System Exam 2 Flashcards
Endocrine System:
Mediator Molecules
Site of Action
Type of target cell
Time/Duration
Mediator Molecules: Hormones in blood
Site of Action: Far, bind to receptors on organs or tissues
Type of target cell: many cells
Time/Duration: seconds to days, long
Endocrine glands release hormones into interstitial fluid and blood. What are the two types of hormones
Circulating, local
Circulating Hormones
Secrete into interstitial fluid
Diffuse to blood vessels and circulate
Bind to receptors
Inactivated by liver, excreted by kidney
Local Hormones (Autocrine and Paracrine)
Autocrine: Secreted into extracellular fluid (don’t enter blood)
Hormones act on same cell
Paracrine: Secreted into extracellular fluid (no blood)
Short distance
Hormones response depends on what two things
Hormone type
Target Cell
What are the two types of Water Soluble Hormones
Amine: synthesized by modifying A.A. (E, NE, Tryp)
Peptide: Synthesized by large molecules than final hormone (oxytocin, vasopressin)
Water Soluble Hormones functions
Stored in vesicles
Stimuli cells cause exocytosis release
Bind to receptors on surface of target
Hydrophobic: needs indirect GCPR
Three receptors for water-soluble hormones
Single transmembrane protein (EGFR)
Dimer Membrane (insulin)
Seven-transmembrane protein (GCPR *Gs alpha)
GCPR enzymes and channels types and second messengers
Enzyme
Adenylate Cyclase: cAMP
Phospholipase C: IP3, DAG, Calcium
Channels
Ion Channel: Ion
How do you inhibit adenylate cyclase
Gi alpha subunit, blocks activation, decrease cAMP, decrease phosphorylation
How do you inhibit cAMP signaling
Phosphodiesterase, clips bond to make AMP
Phospholipase C - Inositol Phosphate System
Hormone binds
alpha q subunit dissociates
activates phospholipase C -> two second messengers
Diacylglycerol and IP3(Calcium released)
(like indirect GCPR)
Mechanism of Phospholipase C
Phospholipase C:
IP3 binds to Ca2+ channel in ER
Releases Ca2+ from ER into cytoplasm
Either:
-Calcium used for muscle contractions
-PKC binds to DAG (activated) then PKC phosphorylates substrates producing an effect
Opening of Ca2+ channels and opening of K+ channels
Calcium:
binding alpha subunit, Ca2+ released from ER, combines with calmodulin activates protein kinase
Potassium:
beta gamma subunits, open K+ channel, K+ leaves, hyperpolarize cells
Tyrosine Kinase Receptor Mechanism (water soluble)
Hormone Binding
Dimerization
Tyrosine Kinase (TK) activated
TK auto-phosphorylates tyr receptors -> fully activated
Proteins are either activated or inactivated
Types of Lipid-Soluble Hormones
Steroids: synthesized from cholesterol (testosterone, estrogen)
Thyroid Hormone: Iodine to tyrosine synthesis (T3, T4)
*Bind to receptors in cytoplasm or nucleus
Transport and Excretion of Lipid-Soluble Hormones
Circulate bound to transport protein making them water soluble
Produce longterm effects
Excreted by liver or kidney
Lipid-Soluble Hormone Mechanism
Hormone diffuses into cytoplasm
Bind to receptors in cytosol or nucleus
Receptor complex interacts with DNA increasing synthesis of mRNA
mRNA in ribosomes synthesize new proteins
Proteins produce response of the cell to the hormone
A decrease in the total number of target-cell receptors for a given messenger is referred to as receptor ______ ________
down regulation
What are the two parts of the pituitary gland
Anterior - Adenohypophysis
Posterior - Neurohypophysis (non-myelinated)
Does the pituitary gland make the hormones it moves
No, the hypothalamus does
Hormones are stored in vesicles of cell bodies to be transmitted. What are the two nuclei in the hypothalamus that synthesize these hormones
Paraventricular and Supraoptic
Hypothalamic Regulation of Posterior Pituitary
Stimuli increase or decrease action potential
AP is carried by axons from hypothalamus to posterior pituitary
AP releases hormones from axon terminals into circulatory (volt Ca2+)
Hormones pass through circulatory system and influence targets
What are the two polypeptide hormones synthesized in the posterior pituitary
Oxytocin - Paraventricular
Antidiuretic (Vasipressin) - Supraoptic
Antidiuretic Hormone (ADH)
effect
target
receptor
effect: promotes water retention and increases blood pressure
target:
kidneys -> water retention, decrease urine volume
Sweat glands -> decrease water loss by perspiration
Blood Vessels -> vasoconstriction
receptor: V1 and V2 in different tissues
Water effects of ADH in kidneys
-Water moves through aquaporins
-Increase synthesis and membrane insertion of water channels
increase number of channels, increase channel activity
Mechanism of ADH in kidneys
ADH binds to V2 vasopressin receptor
Activates Adenylyl Cyclase in renal cells
increases cAMP and activation of PKA
ADH effects on blood vessels and sweat glands
Blood vessels:
-ADH causes constriction ->increase vascular resistance and blood pressure
-Mediated by V1 receptors (GCPR Phospholipase C) on smooth muscle cells
**muscle contraction need Ca2+ (GCPR) to help constrict muscles
Sweat Glands:
decrease water lost by perspiration
Control of ADH release by osmoreceptors and baroreceptors
Osmoreceptors: (in hypothalamus)
-Respond to change in Na+ (plasma concentration)
-Decrease blood volume, increase osmolality, increase ADH release
Baroreceptors: (in aortic arch carotid sinus)
-Respond to changes in blood pressure -> stretching arterial wall
-Increase blood volume, increase blood pressure, increase wall stretching, decrease ADH release
ADH secretion pathway for high and low blood pressure
High blood pressure
-Activate cells to release ADH
-Nerve impulses take ADH from the axon terminal into bloodstream
-kidneys more water, less sweat, arterioles constrict
Low Blood Pressure
-Inhibits hypothalamic osmoreceptors
-Reduces or stops ADH secretion
Oxytocin
Hormone type
Mechanism
Target Tissue
Cyclic peptide hormone - paraventricular
Mechanism: GPCR receptor -> activate phospholipase C
Target: In pregnancy -> uterus and breasts
Oxytocin effects in pregnant women’s uterus and breasts
Uterus: enhances muscle contraction, Pitcoin (oxytocin injection), helps labor induce by adding K+ causing contraction
Breast: stimulated milk ejection “let down” milk secreted from alveolar cells to nipple
Oxytocin Feedback Mechanism for breast milk
Positive feedback loop
Released during lactation to stimulate milk ejection
Baby sucks and signal send to hypothalamus
Oxytocin made -> milk ejection
What are the five types of anterior pituitary cells
somatotropes
corticotropes
thyrotropes
lactotropes
gonadotropes
What are trophic hormones
They stimulate the release of other hormones in a receptor-mediated and tissue-specific manner (TSH and ACTH)
Hypothalamic Regulation of the Anterior Pituitary
Stimulus
Increased hypothalamus 1 secretion
Increase plasma hormone 1 (portal vessels)
Anterior Pituitary 2 secretion
Increase plasma hormone 2 -> target cells of hormone 2
Third Endocrine Gland, increase hormone secretion 3
Increase plasma hormone 3 -> target cells of hormone 3
Somatotropes:
hormone, location, effect
Growth hormone (GH)
Liver -> secrete IGF-1
Other organs and tissues -> protein synthesis, carb/lipid metabolism
GRH -> growth release
GIH -> growth inhibit
Corticotropes
hormone, location, effect
Adrenocorticotrophic hormone (ACTH)
Melanocyte-stimulating hormone (MSH) - skin pigment
Adrenal Cortex (two hormone) -> secretes cortisol
CRH -> corticotrophin release
Thyrothrophes
hormone, location, effect
Thyroid Stimulating hormone (TSH)
Thyroid (two hormone) -> secretes thyroxine, triiodothyronine
TRH -> thyrotropin release
Lactotrophes
hormone, location, effect
Prolactin
Breast -> breast development and milk production
PRH -> prolactin release
PIH -> prolactin inhibit
Gonadatrophes
hormone, location, effect
follicle-stimulating hormone (FSH)
luteinizing hormone (LH)
Gonads -> germ cell development, secrete male/female hormones
GnRH -> gonadotrophin releasing
What are the mechanisms of the releasing and inhibiting pathways
Only releasing hormones: (GnRH, TRH, CRH)
Negative feedback loop -> not enough hormones, increase to produce
Inhibit and Release: (PRH/PIH, GRH/GIH)
Increase effect -> decrease inhibit, increase release
Decrease effect -> increase inhibit, decrease release
The thyroid gland has two lobes connected by the isthmus, what are the two hormones it produces
Thyroid Hormones
Calcitonin (calcium homeostasis)
What is the central cavity that the follicular cells surround called
colloid (glycoproteins)
What do follicular and parafollicular cells produce
Follicular: glycoproteins thyroglobulin and secrete thyroid hormone
Parafollicular (aka C cells): calcitonin
What is the difference between T3 and T4 and what two things are needed for synthesis done in the follicles
T3 has 3 iodine, T4 has 4 iodine
Need: Tyrosines from TGB and Iodide by diet
Thyroid mechanism steps 1-2
1: Synthesis
TGB synthesized and packed in vesicles in follicle cells, TGB into colloid
2: Iodine Trapping
I2 absorbed and ionized into I− in gut, actively transported with Na+ from blood to follicle cells
Thyroid mechanism steps 3-4
3: Iodide Oxidation
Iodide transported into lumen of follicle, I- to I2 by TPE (Thyroid Peroxidase Enzyme) and transported to colloid
4: Tyrosine Iodination
Thyroid peroxidase links iodine to tyrosine in thyroglobulin –> T1, T2 made
Thyroid mechanism steps 5-6
5: Coupling of T1 and T2
Thyroid peroxidase links MIT and DIT to generate T3 and T4 -> collects in the colloid apart of TGB
6: Thyroglobulin Endocytosis
TGB w/ T3 and T4 brought into cells in vesicles that fuze with lysosomes -> breaks down to release the T3 and T4, I- can be reused
Thyroid mechanism steps 7-8
7: Secretion of T3 and T4
They diffuse into interstitial fluid and brought into blood (T4 more)
8: Transport of T3 and T4
T3 and T4 brought into proteins, Thyroid Binding Globulin bind 75% hormones, Transthyretin and albumin bind remaining hormones (free hormones are active, T3 mainly)
Effects of thyroid hormones
Basal Metabolism (proteins, lipid, carbs)
Body Temperature
Tissue Growth
Catecholamines
Actions of T3 and T4 on metabolism
Increase glucose in the blood
liver synthesis
intestine absorption
use in muscles
T3 and T4 effects on lipid metabolism
-Decrease lipid synthesis
-Increase Lipolysis -> degrade TG produce fatty acids, increase fatty acid in plasma, increase beta-oxidation of FA in liver
-Plasma cholesterol is decreased
Effect of thyroid hormone on growth
-T3 is needed for growth hormone production -> muscle growth, bones
-T3 promotes nervous system development and functions -> myelination, synapse development
-T3 promotes reproductive system development and function -> puberty onset
Effect of thyroid hormone on catecholamines
-T3 upregulates beta-adrenergic receptors in tissues (heart/nervous system)
-Excess T3 potentiate action of catecholamines (increase heart rate)
T3 and T4 metabolism
Deionization main for peripheral metabolism
-D1 and D2 maintain formation of T3 from T4
-D3 -> reverse T3
Degradation and excretion by liver
Mechanism of Thyroid Action (Lipid Soluble)
-Hormones dissociate from proteins and leave blood
-Hormones enter cell by diffusion or transport
-T4 converted to T3 by deiodinases
-T3 enters nucleus bind to receptor
-Regulates gene expression
Hypothyroidism effects
Not enough hormones
-Tiredness
-Cold
-Dry skin
-Weight gain
-Fatigue
Hashimoto’s Disease
Destroy thyroid gland
Circulating antibodies against thyroid peroxidase
Goiter -> large thryoid
Hyperthyroidism effects
Too many hormones
-Hot
-Lose Weight
-Sweating
-Tremor
Grave’s Disease
Autoimmune Disease
-Circulating antibodies against TSH receptor
-Exophthalmos -> bulging eyeballs
The pancreas is both endocrine and exocrine gland. What is the main function of the endocrine pancreas
maintain normal blood glucose levels
What are the cells of the pancreas
Pancreatic Islets
Endocrine cells
-Alpha cells (glucagon) increase blood glucose
-Beta Cells (insulin) decrease blood glucose
-Delta Cells (somatostatin) inhibit hormone secretion
-PP/F Cells (pancreatic polypeptide) pancreatic secretion
Glycemia mechanism
maintenance of glucose homeostasis is glucose tolerance
(low glucose -> glucagon release)
(high glucose -> insulin release)
Synthesis and processing of insulin
- Synthesized as preproinsulin in beta cells
- Processed in ER to proinsulin by removing peptide (A and B chain by disulfide bonds)
- Prolinsulin stored in secretory granules in beta cells
- Processed into insulin and C peptide
- C peptide have no activity
Beta Cells at Rest
Beta cells are hyperpolarized -> inhibition of insulin exocytosis
1. Low glucose in blood
2. Metabolism slows
3. No ATP
4. ATP-K+ channel is open
Beta Cells activated in insulin
- High level of glucose in blood
- Increased glycolysis
- High ATP
- ATP-K+ closed
- Less K+ leaves cells
- Cell Depolarizes
- Ca2+ channel open
- Ca2+ activates and moves vesicles for exocytosis
Activation of Insulin Receptor
Binding of insulin to receptor
Phosphorylation of receptor -> Tyrosine Kinase active
Phosphorylation of signal molecules -> many effects -> glucose uptake
Effects of insulin carbohydrate metabolism in liver, muscle, adipose tissue
↓ Gluconeogenesis (inhibit enzyme)
↑ Glycolysis (degrade glucose into lactate)
↑ Glycogen Synthesis
↓ Glycogenolysis (breakdown glucose)
Effects of insulin lipid metabolism in liver and adipose tissue
↑ Lipogenesis (build fats)
↓ Lipolysis (break fats)
Effects of insulin protein metabolism in muscle
↑ Amino Acid uptake
↑ Protein synthesis
↓ Protein degradation
Incretins in insulin secretion
Incretins are intestinal hormones secreted from L cells in small intestine to circulation
Pancreas: ↑ insulin secretion, ↓ glucagon
GI Track: ↓ gastric empty
Brain: ↓ food intake
What are the two glucagon pathways
Pancreatic alpha cells -> get glucagon
Intestine L-cells -> Incretins (GLP1 and GLP2)
Mechanism of Action of Glucagon
Glucagon binds to glucagon receptor (GCPR)
Stimulation of adenylate cyclase
cAMP used
Phosphorylation activates enzymes for glycogenolysis, gluconeogenesis, lipolysis
Effects of glucagon in liver, muscle, adipose tissue
Opposite of insulin
Somatostatin
Inhibitor of growth hormone release
*Released by delta cells in the pancreas in response to:
-increase in blood glucose and blood amino acids
Paracrine: can inhibit both insulin and glucagon release
Hypoglycemia; treatments, symptoms
most common adverse effect of insulin treatment
could lead to coma
Treatment
- Conscious Patient -> glucose gel, sugar tablet
- Unconscious Patient -> IV glucose, hospital
Symptoms
-Angry
-Shake
-Fast Heartbeat
Gestational diabetes is triggered during
pregnancy
Type 1 diabetes
Destruction of beta cells
When caught 80% of cells are destroyed leading to hyperglycemia
Increased Glucose Levels in blood
Need injections of insulin
Type 2 diabetes
Tissues do not respond well to insulin
↓ Glucose use by cells -> increased blood glucose
Metabolic syndrome
Symptoms:
tired
hungry
tingling of hands and feet
polyuria (peeing)
What are parathyroid glands and parathyroid hormone
Gland: 4 glands in posterior surface of thyroid
Hormone: Made by chief (principle) cells -> increases calcium in blood
-Have to do with calcium homeostasis
In the thyroid gland where is calcitonin made and what does it do
Made in parafollicular cells
Decreases calcium in blood
If calcium is level is too high what does the thyroid gland do
Bones: increase uptake
Intestine: decrease uptake
Urine: decrease uptake
What are the two complexes on the adrenal gland
Adrenal cortex (outside) 80-90% of total
Adrenal Medulla (inside)
What are the three layers of the adrenal cortex and what are the hormones they each release
Zona Glomerulosa -> Aldosterone (mineralocorticiods)
Zona Fasciculata -> Cortisol (glucocorticiods)
Zona Reticularis -> Androgens (sex hormone)
Mineralocorticoids: major hormone and which system
Hormone: aldosterone
System: RAAS -> regulation of blood pressure
Main molecules of RAAS
Renin -> proteolytic enzyme released by kidney
Angiotensin II -> Active molecule
Aldosterone -> final hormone
What is the secretion of aldosterone stimulated by
decrease blood volume
decrease blood pressure
low blood Na+
Angiotensin II can activate the release of ___________ from the pituitary
vasopressin
Aldosterone mechanism of action (Lipid Soluble)
-Binds to mineralocorticoid receptors in the cytoplasm
-Receptor activates transcription in nucleus
-Protein channels and pumps made
-Aldosterone proteins modify proteins
-Increase Na+ absorption and K+ secretion
Glucocorticoids and cortisol effects: hormone, target
Glucose metabolism
Cortisol produced by cortex
Stress hormone: increased release by ACTH
Target: Liver, muscle, adipose tissue
Cortisol Action: Metabolic and Immune system
Metabolic:
↑ Glucose synthesis (meals and stress)
↑ Lipolysis (energy)
Immune system:
-Anti-inflammatory -> inhibits white blood cells, inhibits production of inflammatory molecules
-Immunosuppression -> organ transplant
Cortisol Action: GI tract and Cardiovascular system
GI tract: Stimulation of gastric acid secretion
Cardiovascular system: ↑ Blood pressure by ↑ sensitivity of vasculature to E and NE
What kind of receptor is glucocorticoids
Lipid: intracellular receptor -> gene expression
Gonadocorticoids
Secreted molecules called androgens *testosterone
Androgens: onset puberty, sex characteristics, sex drive in females
Hormones in Adrenal Medulla
Synthesized by chromaffin cells
E - 80% NE - 20%
Innervated by cholinergic preganglionic neurons
Catecholamine Actions
E and NE fight or flight -> stress
Adrenergic receptors
Blood pressure and fuels metabolism
