Endocrine 1 Flashcards
Steroid Hormone
Secreted from..
Obtained from..
Synthesis
Hydrophobic – can pass thru cell membrane
Act as primary messengers and directly interact w DNA
Secreted from: adrenal cortex (cortisol, aldosterone), testes (testosterone), ovaries and placenta (estrogen, progesterone)
Cholesterol obtained from: animal fat in diet, steroidogenic endocrine cells and liver cells
6-C side chain cleaved from cholesterol to form pregnenolone in mitochondria
Pregnenolone travels to smooth ER
Other enzymes (processes) produce diff steroid molecules
Very little steroid hormone storage –synthesized on demand and secreted by diffusion thru cell membrane
Peptides/Protein Hormones
Typically charged (hydrophilic, polar) --may not pass thru cell membrane Act via 2nd messenger system
Secreted from: pituitary (ACTH, GH, TSH, ADH, oxytocin), parathyroid (PTH), pancreas (insulin, glucagon)
Peptide hormones synthesized at ribosomes, stored in vesicles, secreted on demand
Preprohormone modified by posttranslational processing to prohormone to create a mature hormone
Insulin Synthesis
Synthesized in beta-cells of islets of Langerhans
Consists of 2 peptide chains (A, B) which are connected by disulfide bonds
1) P of preproinsulin cleaved to produce proinsulin (in ER)
2) Proinsulin moves in vesicles into Golgi
3) 3 disulfide bonds fold proinsulin and link A and B
4) C cleaved from proinsulin to form mature insulin
5) Insulin and C stored 1:1 in vesicles awaiting release
6) Depolarization=exocytosis to blood
Amines Hormones (tyrosine derivatives)
Secreted from: thyroid gland (T4, T3)–steroid-like, adrenal medulla (epinephrine, NE)–protein-like
Catecholamine-secreting cells need tyrosine to produce dopamine, NE, E
In the thyroid gland, enzymatic reactions in the follicle cells and colloid start with tyrosine to produce iodothyronines
Tryptophan is modified biochemically in the pineal gland to produce melatonin
Hormone Transport & Clearance
Steroid and thyroid hormones transported thru blood by being bound to carrier proteins (serum pr bind them and increase hormone solubility in water)
Hormones are cleared by: metabolic destruction by tissue, binding w tissues, excretion by liver into bile, excretion by kidneys into urine
Water soluble hormones (peptides and catecholamines): degraded by enzymes in blood/tissue and excreted by kidneys or liver
• Short half-life: less than a minute
Lipid soluble hormones (steroids): plasma protein bound and are cleared slowly
• Half-life: hours to days
Intracellular receptors
Lipid soluble hormones (like steroids)–receptors inside cell (cytoplasm or in the nucleus)=intracellular receptors Alter gene expression by turning transcription/translation on/off =affect production of new pr (genomic effect) New protein (can be enzyme or structural pr) carry out target cells physiological responses (this takes time)
G-protein-coupled membrane receptors
Water soluble peptide and amines hormones –bind receptor molecules located in cell membrane and binding sites that face extracellular fluid
Mediate hormones actions by regulating ion-channel permeability or by activating intracellular 2nd messenger system
Adenylyl cyclase-cAMP
Secondary Messenger
- Activated G-pr stim adenylyl cyclase
- Catalyzes conversion of ATP to cAMP inside cell
- Active cAMP-dependent pr- kinases will phosphorylate (activate) specific pr- triggering biochem rxns leading to cell’s response to hormone
Cell membrane phospholipid
Secondary Messenger
- Hormone binding causes activation of enzyme phospholipase C which breaks down PIP2 into inositol triphosphate (IP3) and diacylglycerol (DAG)
- IP3 mobilizes Ca2+ from intracellular stores causing smooth muscle contraction and changes in cell secretion
- DAG (membrane-bound) will activate PKC which will phosphorylate large # of pr leading to cell’s response
Calcium-calmodulin
Secondary Messenger
- Operates in response to entry of Ca2+
- Ca2+ binds to 4 sites on calmodulin causing conformational change
- This causes activation/inhibition of pr- kinases within cell
Enzyme-linked membrane receptors
Some peptide hormones (insulin and growth hormone) bind to enzyme-linked membrane receptors (which faces ECF) and change activities of existing pr- (delay for min)
Ligand binds=>activates active site=>GTP to cGMP
BAT vs WAT & Leptin
Inducing lipolysis (release fatty acids) in white adipose tissue (WAT) –appetite Inducing thermogenesis in brown adipose tissue (BAT) –body temp
Leptin & Obesity
Leptin: hormone released from fat cells located in adipose tissue, send signals to hypothalamus
When ppl diet, they eat less=their fat cells lose some fat=decrease amount of leptin produced
Leptin level goes below personal leptin threshold =brain sense starvation
Brain believes it doesn’t have enough energy=stim huge appetite and increased food intake
Extremely rare genetic condition called congenital leptin deficiency (body cannot produce leptin)
Absence of leptin make body think it does not have any fat resulting in uncontrolled food intake and severe childhood obesity
Obese ppl have unusually high levels of leptin b/c brain does not respond to leptin, so they keep eating despite adequate fat stores (known as “leptin resistance”)
Downregulation vs Upregulation
Downregulation: when hormone increases, cell decreased number of receptors –become less reactive to hormone levels
Upregulation: when hormone decreases, cells increased number of receptors –become more reactive to hormone levels
Permissive, Synergistic, Antagonistic effects
- Permissive effect: in which the presence of 1 hormone enables another hormone to act
- Synergistic effect: in which w hormones w similar effects produce an amplified response
- Antagonistic effect: in which two hormones have opposing effects
EX: insulin and glucagon
