ENDOCRINE Flashcards
2 major regulatory/ control systems
endocrine
nervous system
endocrine system
(messenger, speed, purpose)
Slow acting
Long term slow response
Hormone messengers
Regulates activities of longer duration than speed
(growth, development, reproduction)
Maintains homeostasis
Long term slow response
Hormonal signaling (reach all body cells by affects target cells)
endocrine system
(messenger, speed, purpose)
Slow acting
Long term slow response
Hormone messengers
Regulates activities of longer duration than speed
(growth, development, reproduction)
Maintains homeostasis
Long term slow response
Hormonal signaling (reach all body cells by affects target cells)
nervouvs syste, (messenger, speed, function)
Fast acting
Short term quick response
Neurotransmitters
Regulates activity of muscles and glands
Quick responses
Local signaling
(paracrine – nearby, synaptic
hormones definition
substances released by endocrine glands, transported throughout bloodstream to target tissues where they act to regulate specific functions
hormones activity
1) Exerts effect in low conc
2) Bind to target cell receptors to initiate biochemical reaction
3) Each hormone act on specific receptor on target tissue
□ SELECTIVITY: hormone-specific receptors in (target cell’s cell mem. Cytoplasm/ nucleus)
classification of hormones
1) endocrine gland (ductless vs exocrine)
2) chemical nature (peptide, steroids,amines)
endocrine definition
ductless, produce hormones into surrounding tissue fluid
central endocrine glands
pineal, hypothalamus, pituitary
peripheral endocrine gland
thyroid, thymus, adrenal, pancreas, ovary, testis
secondary endocrine glands definition and eg
hormones secreted by organs which also have other major functions
kidney, heart, stomach, SI, skeleton, skin, adipose tissue, placenta
exocrine glands
nonhormonal substance, ducts that carry substances to mem surface
eg: Sweat, saliva glands
hypothalamus hormones
Releasing & inhibiting hormones
TRH, CRH, GnRH, GHRH, PRH
GHIH, PIH
pituitary anterior lobe hormones
Luteinising hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin (PRL)
growth hormone (GH)
adrenocorticotropin (ACTH)
Thyroid-stimulating hormone (TSH)
posterior lobe pituitary hormones
ADH/ vasopressin
Oxytocin
(produced by hypo, secreted by pituitary)
Thyroid gland hormones
Thyroxine (T4)
3,5,3’ - triiodothyronine (T3)
Calcitonin
parathyroid gland hormones
PTH -parathyroid hormone
adrenal gland hormones
CORTEX = Cortisol, aldosterone, androgens (puberty)
MEDULLA = Epinephrine, norepinephrine
gonads - testis hormones
Testosterone
estradiol
inhibin
Mullerian-inhibiting hormone (MIH)
gonads - overy hormones
Estradiol
progesterone
inhibin
placenta hormones
Human chorionic gonadotropin (hCG)
Progesterone
estrogen
pancreas hormones
Insulin, glucagon, somatostatin
pineal hormone
Melatonin (regulates body clock)
hormone disrupters effect
- mimic hormone action
F: incr breast tumours
M: fall sperm count, cryptorchidism (testes undescended)
Animal: gender bending (hermaphrodites both F, M)
hydrophilic hormones activity
Hydrophilic hormones: dissolved & transported free in blood
binds to cell surface proteins
Cell mem receptor/ plasma protein: 50% catecholamines, protein hormones
hydrophilic hormones 2 types
proteins/ peptide hormone
amines
lipophilic hormones group
steroids
hydrophobic hormone
activity
Hydrophobic hormones: bound to plasma proteins (binds to intracellular proteins)
Cross plasma mem, act on receptors inside cell
Steroid hormones, thyroid hormones
(hydrophobic
protein/ peptide hormone eg
Follicle-stimulating hormone (FSH)
Prolactin, growth hormone, adrenocorticotropin
Thyroid-stimulating hormone (TSH)
ADH/ vasopressim. oxytocin
Calcitonin
Parathyroid hormone (PTH)
inhibin
Human chorionic gonadotropin (hCG)
Insulin, glucagon,
steroid hormone eg
(adrenal cortex) Cortisol, aldosterone
(gonads)
Testosterone,
Estradiol, progesterone
(kidney) Calcitriol (vit D)
amines hormone eg
Thyroxine (T4)
3,5,3’ - triiodothyronine (T3)
Melatonin
(adrenal medulla) Catecholamines (Epinephrine, norepinephrine )
mechanism after hormone binds to receptor
1) signal amplification (2nd messenger, PK cascade)
2) hormone activate genes, alter proteins synthesised
3) alter channel permeability (insulin GLUT4)
hormone imablance caused by
result in excess or deficiency target-cell responsiveness
hormones test
Blood (plasma)
Urine (hormone excreted via kidney)
Saliva
Other biologic sample (tissue - hormone internalized by target cells)
1) Radioimmunoassay (RIA)
2) Enzyme-linked immunosorbent assay (ELISA)
- Pregnancy test kits (for hCG hormone – sandwiched between 2 AB)
negative feedback
inhibit initial stimulus, restore body to balanced state
thyroid gland location
neck, anterior surface of trachea, below larynx
thyroid gland structure
○ 2 lobes connected by isthmus
○ Extensive blood supply: hormone released directly into bloodstream
(Deep red colour)
thyroid gland cell types
1) Follicle cells
□ Synthesis thyroglobulin (globular proteins)
□ Secreted into colloid of thyroid follicles
2) Thyroid follicles
□ Functional unit for Thyroid hormone production
3) Colloid
□ Extracellular space where thyroglobulin with attached iodine atoms are stored (T3, T4)
4) C cells/ parafollicular
□ (in between follicles)
□ Secrete calcitonin (regulate Ca levels in blood)
thyroid hormone synthesis requires which 2 basic ingredients
1) Tyrosine – an aa synthesised in suff amts by body
2) Iodine – from dietary intake
□ To be reduced to I- (iodide) before absorption by SI
occurs on Thyroglobulin – produced by thyroid follicular cells
thyroid production step 1 (TG secretion, exocytosis)
TG produced by ER/ GA of thyroid follicular cells
Tyrosine + TG molecules = Tyrosine-containing TG: backbone
Exported in vesicles from follicular cells into colloid by exocytosis
thyroid hormone synthesis step 2
- iodide trapping (iodine oxidation)
Thyroid gland capture I- from blood, transfer to colloid (iodide pump Na+ K+ pump)
Follicular cell --> colloid (iodide pump) transport Na into follicular cell down conc gradient Transport I- into cell against con gradient
I- oxidised ——> active iodide (mem bound enzyme: Thyroperoxidase TPO)
Active iodide exists through channel into colloid
step 3 (iodination)
In colloid, TPO attach iodide to tyrosine (of TG mole)
1 I = MIT (mono-iodotyrosine) 2 I = DIT (di-iodotyrosine))
step 4 (coupling, conjugation)
MIT + DIT = T3 (1+2)
DIT + DIT = T4 (2+2)
Attached to TG by peptide bonds
within colloids
step 5 (colloid resorption, endocytosis)
Stimulus for thyroid hormone
follicular cells internalise portion of Tg-hormone complex (phagocytosis piece of colloid)
step 6 (Thyroglobin proteolysis, break from TG backbone)
Lysosome attack engulfed vesicle, split iodinated products from TG
T3, T4 diffuse freely follicular cells –> blood/ plasma protein/ transport// storage – bound to TG store in follicular lumen
Iodinase enzyme: remove iodide from MIT/ DIT (NOT T3, T4)
Freed I- recycled for synthesis of more hormones
thyroid hormone metabolism, excretion
- high conc plasma (90% released from thyroid)
- 80% of T3 <—- T4
- metabolic inactivation (T4>3): conjugation w/ glucuronic acid in liver.
-conjugate secreted into bile, faeces (Elim)
- small amt in urine
thyroid hormone negative feedback controlled by
HPT (hypothalamus, piuitary, thyroid axis) axis
hypo hormones (TRH)
ant pitui hormone (TSH/ thyrotrropin)
thyroid hormone (T3,4)
thyroid hormone (stimulating pathway)
1) TH low, stimulate pitui and hypotha
2) TSH from anterior pituitary gland
3) stimulate (2nd messenger, incr cAMP, PKA, PLC = Ca2+ release)
4) incr synthesis and secretion of TH (iodine trapping, iodination, coupling, colloid resorption, TG proteolysis)
T3, T4 physiologic effects
1) basal metabolic rate
2) sympathomimetic effect
3) CVS effect
4) bone growth, maturation
5) nervous system development
6) incr metabolism of proteins, lipis, carbs
BMR levels
euthyroid, normal = 150ml/min
hyperthyroid = 400ml/min
why incr BMR
□ Incr size, number of mitochondria
□ Incr enzymes that regulate oxidative phosphorylation
□ Incr oxygen consumption, energy use at rest condition
-Incr metabolic activity, more heat prodn (calorigenic effect)
Sympathomimetic effect
-Mimics activation of SNS
-TH increase proliferation of catecholamines (epinephrine, norepinephrine) target cell receptors
□ Incr target-cell responsiveness to catecholamines
Ventilate, sweat,
Cardiovascular effect
- Incr heart responsiveness to catecholamines (E, NE by adrenal medulla)
- Increase HR, force of contraction
- Incr CO
Meets demand of O2 consumption
Normal bone growth and maturation
-TH stimulates GF secretion, incr IGF-1 production by liver
Promote effect of GH, IGF-1 on synthesis of new structural proteins + skeletal growth
Role in normal development of nervous system (brain)
§ Esp in brain during childhood
□ Hypothyroid: growth stunted in children
§ For normal CNS activity in adults
□ Hyperthyroid: hyperactive, unable to process info
Increase metabolism of proteins, lipids, carbohydrates
Synthesis but degradation (metabolism)
- mobilisation of endogenous proteins, carb, fat
Hyperthyroid: prevents weight gain due to high metabolism
hypothyroid causes
1) Primary failure of thyroid gland itself
2) 2nd to deficiency of TRH, TSH, both
3) Inadequate dietary supply of iodine
hypothyroid symptoms
LOW METABOLIC ACTIVITY
Cold
Hair loss, brittle nails, dry skin
Constipation
Muscle ache, weak
Slow speech
Menstrual disturbances
Dull-blank expression
Extreme fatigue
Weight gain
Cardiac complications
- bradycardia
hyperthyroidism causes
1) autoimmune Graves disease (prodn TSI - stimulating immunoglobulins)
2) 2nd to excess of TRH, TSH, both
3) Hypersecreting thyroid tumour
diffuse goiter
- enlarged thyroid
- from incr production of TSH
(by pituitary gland --> which acts on thyroid gland)
hyperthyroidism symptoms
Tremor
HR incr, BP
Yawn, fatigue
Restless
Amenorrhea
Heat
Diarrhea
Irritability
Sweat
Muscle waste, weight loss
Amenorrhea (no period)
exophthalmos
BULGING EYES (Exophthalmos) cause
- fluid retention behind eyeballs, bulge forward. Cytokines promote inflamm, oedema
hyperthyroid treatment
- Anti-thyroid drugs
a. Interfere with TH synthesis
b. Block uptake of I- (step2)
c. Drug inhibit TPO (iodination 2) - Prevent iodine coupling to thyroglobulin (MIT) (step 3)
- Surgical removal of portion of over-secreting thyroid gland
a. Risk hypothyroidism
b. Thyroid replacement surgery - Administer radioactive iodine
a. Destroy thyroid cells
b. Reduce amt of thyroxine (T4)
c. Reduce size of gland
treat hypothyroidism
- Thyroid replacement therapy
- Iodine diet
pancreas exocrine
Acinar and duct cells
NaHCO3- solution, digestive enzymes
pancreas endocrine
□ Hormones into bloodstream
□ β Cell –> insulin, amylin
□ α Cell –> glucagon
□ D Cell –> somatostatin
High capillary network!
insulin glucose control pathway
1) Glucose enter by passive facilitated diffusion (GLUT2)
2) Convert to glucose-6-phosphate (GLYCOLYSIS)
3) Krebs cycle (mitochondria)
4) ATP act on ATP-sensitive K+ channel, closing it
5) K+ in cell, depolarization
6) Acts on voltage gated Ca2+ channel
7) Excitation-secretion coupling
8) Release Ca2+
9) Stimulate insulin vesicles to be secreted out of β Cell
10) Reduce BGL to normal 4-6nM
GLUT uses
• GLUT 4: muscle, adipose tissue
• GLUT2: kidney, liver, pancreatic b cell
• GLUT3: neurons
insulin functions
Increase uptake of glucose, translocate GLUT 4
Glycogenesis (glucose –> glycogen store liver, muscles)
lipogenesis (FFA–> TG in adipose tissue)
Proteogenesis (aa –> proteins in muscle)
glucagon MOA
1) Stimulate α Cell
2) Mobilise energy-rich molecules from stores
3) Incr BGL
glucagon functions
• Glycogenolysis
• Glycogen –> glucose
• Lipolysis
• TGL –> FFA –> glycerol + ketones
• Proteolysis
• Protein –> aa
• Gluconeogenesis
• Aa –> glucose
• Glycerol –> glucose
type 1 DM cause
Insulin-dependent diabetes
Childhood-onset/ juvenile
5-10%
Autoimmune process (β Cell no longer makes insulin)
• Genetics
• Environmental factors
type II causes
Non-insulin dependent
Adult-onset
90-95%
Insulin resistance
• Makes insulin, but not used well
• Lifestyle (obesity)
• Genetics (obesity)
• Environmental factors
ACUTE consequences of DM
1) polyuria, polydipsia (thirst) –> renal failure
2) polyphagia (appetite)
3) ketosis (rapid breathing) –> metabolic acidosis –> diabetic coma
4) weight loss (muscle waste, worsen hypergly)
5) DEATH
CHRONIC conseq of DM
§ Degenerative blood vessels
□ Microvascular: retinopathy, nerve damage, kidney failure
□ Macrovascular: stroke, heart attack, reduce blood circ
