Principles of Endocrinology Flashcards
(43 cards)
1
Q
Hormone
A
Chemical secreted in trace amounts by one or more cells (and carried in the bloodstream to another cell) where it modulates a specific biochemical or physiological response
2
Q
What is the difference between endocrine and exocrine?
A
- Endocrine: through blood
- Exocrine: through duct
3
Q
Gland
A
Organ which can secrete a particular chemical substance for use within the body or into the surroundings (single gland may secrete multiple hormones but not all glands secrete hormones) (ex: salivary gland)
4
Q
Endocrine signaling
A
Uses circulating system to transport ligand to target cells
5
Q
Paracrine Signaling
A
Ligand acts on nearby cells (ex: synapse (neurocrine))
6
Q
Autocrine Signaling
A
Ligand acts on secreting cell
7
Q
Tropic Hormone
A
Hormone that targets another endocrine tissue
8
Q
Protein and Peptide Hormones
A
- Few amino acids or hundreds
- Linear, ring structure or dimers
- Transcription and translation
- One gene can produce different proteins (alternative splicing)
- Post-translational regulation can also lead to several products
- Ex: Proopiomelanocortin (POMC): mutation impacts metabolism and stress
9
Q
Peptide Hormone Production
A
- Transcription (Nucleus)
- Translation (ER: ribosomes)
- Processing (ER -> vesicles -> Golgi)
- Packaging (Golgi -> secretory vesicles -> secretion)
- Preprohormone (ER) -> Prohormone (vesicle) -> hormone -> degraded or reuptake
10
Q
Regulated Secretion
A
- Peptide hormones
- cell stores hormone in secretory granules and releases them in bursts when stimulated
- Most common
11
Q
Constitutive Secretion
A
- Peptide hormones
- Cell does not store hormone, but secretes it from secretory vesicles as it is synthesized
12
Q
Neurotransmitters
A
- Enzymatically modified amino acids
- Synthesized by neurons and released into the synaptic cleft
13
Q
Neurochemically Active Amino Acids
A
- Fast excitatory/inhibitory transmission
- Glutamate (+): exhibitory
- GABA (-): inhibitory
14
Q
Monoamines
A
- One amino acid connected to aromatic ring
- Modulation of network activity (slower)
- ex: Catecholamines: Dopamine (DA), Norepinephrine (NE, NA), Epinephrine, Serotonin
15
Q
Peptides (Neuromodulator Peptides)
A
- Slower modulation of circuit function
- ex: Cannabinoid, oxytocin, orexin, CART
16
Q
Acetylcholine
A
Synthesized via enzymatic modification of precursors acetyl-CoA and choline
17
Q
Steroid Hormone Synthesis
A
- Synthesis stimulated by tropic peptide hormones
- Mainly produced in adrenal cortex and gonads
18
Q
Cholesterol
A
Precursor for all steroid hormones and vitamin D3 and steroid hormone metabolites and bile acids
19
Q
Explain the two types of corticosteroids produced in the adrenal cortex.
A
- Glucocorticoids: glucose + cortex + steroid; role in glucose metabolism, immune/stress response
- Cortisol, corticosterone, cortisone - Mineralocorticoids: regulates electrolytes and fluid balance (aldosterone)
20
Q
What type of corticosteroids are produced in the zona glomerulosa of the adrenal cortex?
A
Mineralocorticoids
21
Q
What type of corticosteroids are produced in the zona fasiculata of the adrenal cortex?
A
Glucocorticoids
22
Q
What type of corticosteroids are produced in the zona reticularis of the adrenal cortex?
A
Sex steroids
23
Q
What is produced in the adrenal medulla?
A
Catecholamines
24
Q
What is the rate limiting step in steroid hormone synthesis?
A
- Cholesterol -> Pregnenolone
- Side chain cleavage
25
Adrenal Medulla
- Derives from ectoderm (neural crest)
- Contain chromaffin cells
- Sympathetic innervation
26
Adrenal Cortex
- Develops from mesoderm
- Divided into three zones (zona glomerulosa, zona fasiculata, and zona reticularis)
27
Modified Fatty Acids
- Eicosanoids are derived from 20 carbons PUFA (arachidonic acid)
- Include the prostaglandins (PG), thromboxanes (TX), leukotrienes (LT), and lipoxins (LX)
- Autocrine and paracrine action
- Most prostaglandins have five membered rings with substituent determining the subclass (letter)
- Number following the third letter designates the number of double bonds in the two-side chain
28
Modified Fatty Acid Hormone Synthesis
1. Arachidonic acid is released from the membrane by phospholipase A2 (Rate-limiting step)
2. COX produces the cyclic endoperoxide intermediates (PGG2 and PGH2)
3. Eicosanoids
- Anti-inflammatory steroids inhibit phospholipase A2
- COX inhibitor (aspirin)
29
Explain the difference between humoral hormonal, and neural.
1. Humoral: response to changes in composition of extracellular fluids (levels of ion/nutrients in the blood)
2. Hormonal: stimulated by other hormones (presence or absence)
3. Neural: stimulated by nerves
30
Principle of homeostasis
- Hormone is released based on the requirement for a biological response
- Once response is met, secretion is inhibited to prevent over response
- Most endocrine systems have feedback loops to limit or regulate hormone synthesis and/or release
- Feedback can be direct or indirect via the CNS
31
Receptor Signaling
- Presence of specific protein receptor in cell is the target for hormone
- Receptors are subject to removal/inactivation
32
Protein based hormone signaling
- Prostaglandins included
- Short half-life
- Cell surface receptors
33
Steroid based hormone signaling
- Thyroid hormone included
- Long half-life
- Intracellular nuclear proteins
34
Explain the two domains of receptors.
1. Ligand-binding domain (stereospecific)
2. Effector domain that responds to the presence of the hormone and initiates biological response
35
Cell Surface Receptors
- Three domains:
1. Extracellular component
2. Membrane-spanning component (20-25 AA organized into an alpha-helix to cross the membrane)
3. Intracellular component
- Can be a single polypeptide (N-terminus outside the cell, C-terminus inside)
- Can be composed of subunits (ion channels)
- Classified based on number of membrane spanning regions and cytoplasmic part response to ligand binding
- Ex: GPCRs
36
G-Protein Coupled Receptors (GPCRs)
- Most common, ligand and response specific
- Act via G protein complex to activate enzymes
- 7 transmembrane domains (single polypeptide chain)
- Engage second messengers (ex: IP3, DAG, Ca2+, cAMP) for signal amplification
- Ex: GnRH-R, muscarinic AChR
- Inactive G-proteins: three subunits in a heterotrimer (alpha, beta, gamma)
- Subunits (alpha and gamma) have lipid moieties binding them to the membrane
- GDP (guanosine diphosphate) is bound to the alpha subunit
- Ligand binds to the receptor -> GDP is replaced with GTP
- Receptor acts as the guanine nucleotide exchange factor (GEF)
- alpha-subunit dissociates and moves through the membrane to a nearby protein (enzyme, ion channel)
37
Tyrosine Kinase Receptors
- Single membrane spanning receptors
- Dimerize upon ligand binding
- Exception: IR and IGF-1R dimers of hemireceptors
- Kinase activity: main cytoplasmic constituent and initiator of signal transduction
- Main signaling pathway engaged by receptor tyrosine kinases (ex: MAP kinase cascade, protein kinase C pathway, JAK/STAT pathway)
- Each phosphorylation steps: amplification of the response (small concentration of hormone)
38
Ligand Gated Ion Channels
- Ion specific channels open when ligand binds to the receptor
- Rapid movement of ion along concentration gradient (first message)
- Ex: nicotinic AChR, 5-HT3R (serotonin)
- 5 Subunits, spanning the membrane 4 times to form a cylinder
39
Cell Surface Receptor Signaling
- Ligand binding to the exterior of the cell and initiate a signaling cascade on the interior of the cell that changes "physiology" in the target cell
- Can change: protein transport, protein synthesis, secretion, ion channels, gene expression
40
Nuclear Receptors
- Found in the nucleus or cytoplasm (will move to nucleus) of target cells
- May be bound to corepressor (chaperone) molecules which suppress DNA transcription
- Structure include a DNA-binding domain (highly conserved domain (C) and variable domain (D)) (regulation of gene expression/transcription)
- DNA-binding site consists of 2 zinc fingers
- Binds DNA at the hormone response element (HRE)
- Ligand binding domain is less conserved but adopts approximately the same three-dimensional structure in all the receptor (12 alpha-helices arranged in three layers)
- Regulates gene transcription
- Response can include an early and delayed response in transcription of target genes
41
Explain the receptor/hormone interaction.
- [R]: # receptor on cells
- [L]: ligand concentration
- [RL]: ligand bind to receptor
- KD (Dissociation constant): ligand concentration at which receptor is half saturated with ligand
- KD = [R][L]/[RL]
- Receptors are cellular proteins with: high affinity, specificity, saturability
- Receptors have agonists and antagonists
42
What can affect the biological response?
1. Concentration ligand [L]: rate of production, rate of degradation/elimination
2. Number of available receptors on the cell [R]cell: sensitivity, competitive binding, saturation
43
Explain diabetes in regards to a problem with the receptor versus the ligand.
1. Type 1: Insulin dependent (IDDM), normal R, no pancreatic beta-cells (no L)
2. Type 2: Non-insulin dependent (NIDDM), impaired R function, increased circulating L
