3. Endocrine Pathology I Flashcards
Introduction to the Endocrine System
- Endocrinology is about communication systems and information transfer.
- Actions mediated by hormones.
• Hormone:
• Molecule that functions as a message within an organism: conveys information.
• No ____ similarity: many types of molecules are hormones.
• A molecule is a hormone only when described in the context of its role in a biological communication
system.
• Definition of a hormone requires testing of that molecule in a biological response system, running a
____.
• Endocrine glands synthesize and store hormones:
• Sensing and signaling system which regulates the duration and magnitude of hormone release via feedback from the target cell.
chemical
bioassay
Functions of the Endocrine System
The Endocrine System regulates:
Maintenance of ____: stability of internal environment.
Integration and regulation of growth and development.
Reproduction: control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.
Uses chemical messengers to relay information and instructions between cells:
• ____ communication.
• Paracrine communication.
• ____ communication.
homeostasis
direct
endocrine
Elements of an Endocrine System
• ____ = Sending Cell.
• Signal = Hormone.
• Nondestructive Transport Medium = ____ and Hormone Binders.
• Selective Receiver = Receptor Protein.
• ____ = Transducer Proteins and Second Messengers.
• Amplifier = Transducer/Effector Enzymes.
• ____ = Effector Proteins.
• Response = Cellular Response (including secondary Hormones).
sender
serum
transducer
effector
Types of Cell-Cell Signaling
• Classic endocrine signaling: hormones from endocrine glands travel via ____ to target cells (____ are a special case of hormones released from synapses; sometimes called “neuroendocrine signaling”)
• Paracrine hormones act on ____ cells.
• Autocrine hormones are released and act on the
cell that secreted ____.
bloodstream
neurohormones
adjacent
them
Endocrine vs. Nervous System
- Similarities:
- Major communication systems in the body.
- Integrate stimuli and responses to changes in external and internal environment.
- Crucial to coordinated functions of highly differentiated cells, tissues and organs.
• Differences:
• Unlike the nervous system, the endocrine system is anatomically
____.
• Usually the endocrine system shows a ____ response to stimuli and produces ____-lasting effects.
discontinuous
slower
longer
Endocrine vs. Nervous System: Dual Hormone/Neurotransmitters
Oxytocin
Hormone: ____
NT: Attenuates ____ consolidation and retrieval.
Hormone: ____ letdown.
NT: Stimulates ____, pair bonding and “motherly love”.
Vasopressin
Hormone: ____
NT: Facilitates ____ consolidation and retrieval.
NT: Stimulates ____ promiscuity and inhibits pair bonding.
• Oxy and vasopressin are very similar - \_\_\_\_ hormones • Functions are different bt the nervous and endocrine system ○ A hormone is only a hormone when it's assayed in a particular biological response system ○ Nothing in the chem \_\_\_\_ that tells you that it's a hormone
parturition
memory
milk
monogamy
antidiuretic
memory
male
peptide
structure
NT Receptor
- ____ ligand affinity
- high local cxn
- ____ clearance
- normal ligand-to-receptor distance
- ____ response
- approximate target
Hormone receptor
- ____ ligand affinity
- low local cxn
- ____ clearance
- extensive ligand-to-receptor distance
- ____ to languid response
- “indiscriminate targets”• Differences on the receptor side
○ Same molecules may bind a receptor in the nervous system, and one that may bind one in the endocrine system
• Features that correspond to the actions of the same molecule - whether it’s a NT or a hormone
• Receptors for hormones (molecules that have dual personalities) > high affinity for the ligand for the hormone receptor
○ Binding of a ligand to a receptor at lower aff > generate a more ____ response
§ Higher cxn of the mol to elicit the maximum response possible
§ W a high aff receptor > few molecules will activate the response
low
rapid
rapid
high
slow
slow
graded
Hormonal Classes
- Two general classes based on solubility in water:
- Water-soluble hormones:
- ____ (epinephrine and norepinephrine)
- ____ hormones.
- Lipid-soluble hormones:
- ____ (steroids, eicosanoids)
- ____ acid-derived (thyroid hormones).
catecholamines
peptide/protein
lipids
amino acid-derived
Water-soluble Hormones
• Synthesized in endocrine cells and secreted by ____.
- Freely ____ in the bloodstream:
- May travel free or associated to binding proteins (“carriers”).
- ____ receptors:
- No direct effect on activities ____ target cell.
- Use intracellular ____ to exert effects.
- Results in change in rates of metabolic reactions.• Carriers - albumins and globulins within the blood
• Receptors located at the PM-level of the target cell
○ Hormone doesn’t have to internalize itself to elicit the response - no direct contact of the hormone w the target cell
○ Intercellular intermediates > signaling molecules and cascades are involved in the action of the hormone
exocytosis soluble plasma membrane inside intermediaries
Hormone Types: Catecholamine Hormones
• Water-soluble compounds. • Examples: \_\_\_\_ (adrenaline) and norepinephrine (noradrenaline). • Synthesized from the amino acid \_\_\_\_. • Brain and nerve catecholamines → \_\_\_\_.
• ____ gland catecholamines (epinephrine
and norepinephrine) → hormones.
• Secreted within secretory vesicles by ____.
• Act through surface receptors to generate intracellular ____.
• Mediate responses to acute stress.
epinephrine
tyrosine
hormones
adrenal
exocytosis
second messengers
Hormone Types: Peptide/Protein Hormones
• Most abundant class of hormones.
• ____-soluble, 3 aa to >200 aa in size.
• Commonly synthesized as high ____ precursors, later proteolytically cleaved to the active form of the hormone:
• Translation into a protein precursor: ____.
• Post-translational modification (usu. glycosylation) in the ____.
• Signal peptide of the preprohormone removed to form a ____.
• Prohormone processed into active hormone and packaged into secretory vesicles.
• Alternatively: prohormone is secreted and converted in the ____ into the active hormone:
• Example: ____ - secreted by liver and converted into its active form by
enzymes secreted by kidney and lung.
• >10 AA = protein, not a peptide ○ <10 AA = peptide • Similar to the preproproteins seen in FSI ○ None of the processing is different from what is seen before • Secreted at prohormone ○ Inactive molecules that are converted in active in ECF/BS after further processing
water MW preprohormone ER prohormone extracellular fluid angiotensin
Intracellular Peptide/Protein Hormone Processing
• Extreme example of the intercellular processing of a protein that serves as the precursor for hormones ○ \_\_\_\_ > translated from mRNA from the POMC gene § Only has one exon ○ Large molecule > preprohormone > still has the signal peptide § Elimination of this > prohormone ○ Processing is dramatic > every segment of the molecule in yellow produces an active \_\_\_\_ § Gamma-MSH - one § ACTH - two □ Splits into alpha-MSH and CLIP • Peptide hormones are secreted through regulatory mechanisms, but can undergo extreme processing > all the products here are mol that are bio active as hormones
POMC
hormone
Extracellular Peptide/Protein Hormone Processing
• Another example of extreme hormone processing ○ Formation of angiotensin § Instead of the processing taking place inside the cell/immediate EC surrounding the cell > here it takes place in diff organs □ \_\_\_\_ ® >400 AA ® Produced by liver ® Then processed through proteases/cleavage in diff places: ◊ Protease (renin) in the \_\_\_\_ that cleaves the precursor > angiotensin I ◊ Further processing of ATI: } \_\_\_\_ > ATII } \_\_\_\_ } \_\_\_\_ > ATIV
angiotensinogen I
plasma
lung RBC
kidney
Lipid-soluble Hormones
• Synthesized in endocrine cells but not packaged in secretory granules:
• ____ diffusion out of the endocrine cell and complexed with ____ proteins
(usually blood globulins).
• Hormone-carrier complex travels in the bloodstream to the target cells: hormone is
released from the carrier before ____ the target cell receptor.
• Some lipid-soluble proteins do not use carrier proteins: e.g. ____.
- Intracellular receptors: hormone freely diffuses or is transported across membranes of the target cells.
- Alter rate of ____ transcription in nucleus:
- Change patterns of protein synthesis.
- Directly affect metabolic activity and structure.
- Includes ____ and thyroid hormones.• Mechanism of secretion is different
○ Do not dissolve well in the BS > travel assoc w carrier proteins
○ Only released just before the hormone binds the receptor located at the target cell
• The receptors are located intracellularly, not at the PM
○ Being lipid soluble > hormones can easily diffuse across the PM
passive
carrier
binding
aldosterone
DNA
steroids
Hormone Types: Steroid Hormones
- Examples: ____ hormones and sex hormones.
- Synthesized from ____.
- Lipid-soluble: require ____ bound to carrier proteins.
• Adrenocortical hormones - two types:
• Glucocorticoids: e.g. ____, metabolism of carbohydrates.
• Mineralocorticoids: e.g. ____, regulate electrolytes in the
blood.
• Sex hormones:
• Androgens: e.g. ____; testes.
• Estrogens: e.g. ____; ovaries.
• Sexual development, sexual behavior, other reproductive and non-reproductive functions.
• Act through ____ receptors to regulate specific gene expression.
• Secondary pathway: more rapid effects, mediated by receptors in the
____.
• Most impt steroid hormones are those that are produced by the cortex of the adrenal gland, and the sexual hormones
adrenocortical
cholesterol
transport
cortisol
aldosterone
testosterone
estradiol
nuclear
plasma membrane
