Endocrinology overview Flashcards
Endocrine glands:
specialized groups of cells that release hormones
internally within the body (typically into inters\al space/extracellular
fluid for entry into the bloodstream)
what is Molecular endocrinology
study of the molecular basis for the
synthesis, ac)ons and regula)on of hormones and their receptors
Hormones
chemicals that act as signaling molecules to traffic specific
informa)on from one cell to another
How do hormones travel?
• Hormones travel through a medium, such as the extracellular fluid or the
bloodstream.
• Therefore, can transmit information to distant parts of the body,
and cause responses far from the point of secretion.
what can a single hormone do?
A single hormone might regulate multiple physiological processes
(and have distinct effects in different target cells).
• Physiological process might be regulated by multiple different hormones.
12 general actions of hormones
- fetal development • cell growth (and cancer) • digestion • metabolism of carbohydrates, lipids, proteins/amino acids, nucleic acids • ion and water balance (minerals and water) • renal function • cardiovascular func:on and circulatory system • respiration • skeletal function • reproductive function • immune system func:on • central nervous system function
Dysregulation / dysfunction of hormone levels and in cellular responses
Dysregulation of hormone levels or dysfunction in cellular responses to
hormones can cause pathological changes (i.e., an endocrine disease or
endocrine disorder)
how are Hormone levels in circulation (and hormone actions) tightly
regulated.
This is accomplished by controlling hormone
synthesis/precursor processing/release; controlling ability of hormones to
access target cells; and through hormone removal (degradation)
can hormones regulate their own production ?
Hormones can regulate their own production and release
as well as that for other hormones
Juxtacrine
contact-dependent signaling
between neighboring cells (e.g., via gap
junctions, or between a membrane ligand of
one cell and the cell surface receptor or cell
adhesion molecule of an adjacent cell)
Autocrine
ligand is released by the signaling
cell, then acts on the same cell that produced it
Paracrine:
ligand is released by the signaling
cell, then acts on a nearby cell
Endocrine
ligand is transported by the circulatory system (acts on a distant cell)
Additional organs that also produce hormones
Kidney Heart Adipose tissue Gastrointestinal tract Liver Bone
Classic” endocrine organs contain..
contain ductless glandular structures (groups of cells) that release hormones into the extracellular space where they eventually access circulating plasma
”nontraditional” endocrine organs
also secrete hormones (with important
physiological effects) into the bloodstream
hypothalamus
The hypothalamus is a primary link
between the two systems
Nervous system
also communicates between cells via chemical messengers (ligands & receptors) • Some chemical messengers (e.g., norepinephrine) can be considered as both neurotransmitters and hormones, depending on where they are secreted and act
Key dif in endocrine and nervous system
unlike the endocrine system
(open system of circulating plasma carries
signals), the nervous system uses a combination
of electrical action potentials (along neuron)
plus neurotransmitters across small intercellular
distances
Nervous system vs endocrine system
- how are signals transmitted
Nervous system: signals are transmitted much faster (response times in seconds), more specifically targeted, and generally shorter-lived
Endocrine system: wider range of signal distribution,
and tends to have higher-affinity receptors (therefore
can respond to lower concentrations of ligand), but
takes longer for signals to be spread (response time on
the order of minutes-hours)
Hormones can act in a ___ and __ ….
Hormones can act in autocrine or paracrine fashion without entering circulation, or reach their target cells via the bloodstream (endocrine)
Neurotransmitters
Neurotransmitters: very
targeted/localized effects
Cytokines
are also important cell signaling molecules (autocrine, paracrine, and juxtacrine signaling func)ons) – but are produced by a broad range of cells, and often at lower concentrations than hormones
what have similarties in function to peptide hormone receptors
Major histocompa)bility complex (MHC) class
receptors and Toll-like receptors have
similari)es in func)on to pep)de hormone
receptors
Cross-talk
the immune system is highly
receptive to endocrine signals, and endocrine
tissues are affected by immune modulators,
such as cytokines
e.g., immune cytokines cause release of
adrenocor3cotropin (ACTH), prolac3n, and
Gonadotrophin-releasing hormone (GnRH)
Aside from their functions, other ways to classify hormones… (7)
• By where they’re produced/secreted
• By their receptor sub-type
• By whether they act as a receptor agonist or receptor antagonist
• By key intracellular messengers (e.g., cAMP, cGMP, inositol trisphosphate (IP3), Ca2+)
& effector mechanisms in their signal transduc4on pathway
• By their chemical structure (protein, pep5de, amino acid deriva5ve, monoamine,
steroid, or fa8y acid deriva5ve)
• By their solubility
• By their receptor loca4on (cell surface vs. cytosolic/nuclear)
receptor sub-types (2)
Cell surface receptors: G-protein-coupled receptors, Receptor-enzymes,
Type I cytokine receptors, Ligand-regulated transporters
• Cytosolic or nuclear receptors (intracellular receptors)
Biological activity of a hormone depends on…
Biological activity of a hormone depends on its interactions with specific receptors
Ligand binding to a specific receptor:
causes signal transduction responses (effector systems) in the target cell
Receptor agonist
activates/triggers the effector
mechanisms and elicit a biological response
binds to the receptor
- Often think of think when thinking of hormone signalling
Receptor antagonist:
binds to the receptor but
does not activate the effector mechanisms;
blocks/dampens a biological response (e.g., by
occupying the receptor/blocking access of an agonist)
Partial agonist-partial antagonist
limited ability to
activate the effector mechanisms (response is < half
of a full agonist)
has a less than half full agonist effect . By blocking full response you are damping system so its also antagonist
Mixed agonist-antagonist:
act as agonist in some
cases, antagonist in others (depending on dose,
cell type, and receptor)
Hormone chemical structures
4
• Proteins & peptides
- Might be glycosylated and/or
dimerized to generate their
full biological activity
• Amino acid derivatives,
monoamines
• Steroids
(derived from cholesterol)
• Fatty acid derivatives
Different synthesis & degradation pathwaysProteins & peptides
• Encoded by cellular genes; Increased gene expression is o^en a key part of biosynthesis • Precursor processing, post-translational modification, and/or assembly often required to generate mature, active forms • Hydrophilic • Often stored in secretory vesicles/granules in endocrine cells • Generally act via cell surface receptors (can’t enter the cell)
Amino acid derivatives,
monoamines
Many are derived from amino acids; Sequestering of precursors and increased activity of enzymes responsible for hormone production is often a key part of biosynthesis • Precursor processing, posttranslational modification, and/or assembly often required to generate mature, active forms • Monoamines are hydrophilic; Thyroid hormones are hydrophobic • Monoamines generally act via cell surface receptors; Thyroid hormones generally act via nuclear receptors
Steroids
derived from cholesterol
Derived from cholesterol; Sequestering of cholesterol and increased activity of enzymes responsible for hormone production is often a key part of biosynthesis • Hydrophobic (pass through lipid membranes; not stored in secretory vesicles: synthesized on demand) • Generally act via nuclear receptors, but some activate cell surface receptors
Fatty acid derivatives
Derived enzymatically from fatty acids • Hydrophobic (synthesized on demand) • Very short half-life (autocrine or paracrine signalling; not long-range)… “hormone-like” • Prostaglandins: involved in mediating responses to injury/illness (control inflammation, blood flow, etc.) • Generally act via cell surface receptors
Additivity
Effects of two (or more) hormones together is
equivalent to the sum of the effects of those
hormones alone
1+1 = 2
Example: Combined effect (on blood glucose) of Glucagon + Epinephrine together
Synergy
Effects of two (or more) hormones together is
greater than the sum of the effects of those
hormones alone
1 + 1 > 2
Example: Combined effect (on blood glucose) of Glucagon + Epinephrine + Cortisol together
Hormone levels and actions must be tightly regulated. Accomplished by:
- Controlling hormone synthesis/precursor processing/release
- Controlling ability of hormones to access target cells/receptors
- Hormone metabolism
Controlling hormone synthesis/precursor processing/release
• Synthesis (e.g., gene expression, precursor availability, enzyme activity)
• Processing (e.g., prohormone conversion/cleavage, modification or assembly)
• Secretion (controlled by signaling events triggered by
exogenous regulators/2nd messengers)
Controlling ability of hormones to access target cells/receptors
- Hormone transport (e.g., blood binding proteins)
- Changes to receptor expression or cellular localization
- Interactions with other regulatory proteins/hormones (e.g., receptor antagonists)
Hormone metabolism
- Conversions/structural changes that increase or decrease activity of hormone
- Degradation of ligand (and/or receptor) over time
Many hormone levels are controlled
___ or ___ by the biological
activity they control (output)
directly, indirectly
Negative feedback loop:
Response tends to return variable back to original level (holding a set point to maintain homeostasis)
Positive feedback loop:
Response changes further changes from a set point… amplifies changes. Specific threshold or separate input is needed to limit the positive feedback loop.
Feedback loop
effector -> variable (External influence
or disturbance) -> sensor -> back to effector
There may be ___ in a feedback loop
multiple steps/levels
The “product” feeding back can be levels of ….
an inorganic ion
or metabolite, or a hormone in an endocrine cascade
Tropic hormone:
a hormone
that cause the release of
another hormone
Input
Input: change in
extracellular
environment
or innervation
Only ___ glands
involved
(no CNS)
- Feedback loops
Only peripheral
endocrine glands
involved
(no CNS)
Hormones in plasma
either free form
(= biologically active form) or bound to other
molecules, e.g. blood binding proteins
Blood binding proteins affect the controlled release
and stability of the pool of hormones by
Make the hormone soluble in plasma (e.g.,
steroid hormones are hydrophobic – low
solubility in aqueous solutions on their own)
• Provides reservoir of hormone that exchanges
with free hormone fraction (making hormone
pool more stable, less dependent on
synthesis/release)
- More uniform/distant distribution
- Slowing hormone metabolism/breakdown
what is not limited to hydrophobic hormones
Blood binding proteins affect the controlled release
and stability of the pool of hormones
e.g., Growth Hormone and Insulin-like growth factor
1 are proteins with specific blood binding proteins.
Albumins:
a family of water-soluble globular
proteins
Serum albumin
• Produced by the liver
• The most abundant blood protein in mammals
• Binds to a range of molecules (with varying
degrees of affinity), including steroids,
fatty acids, & thyroid hormones
Globulins
another family of globular proteins
Interactions between hormones and their receptors depends on:
- Number of receptors
- Affinity of the hormone for the receptor
- Concentration of circulating hormone
Regulation at the level of the receptors is also an important point of
endocrine function control..
Increasing or decreasing receptor synthesis
• Internalization vs. cell membrane localization of cell surface receptors
• Desensitization of receptors (“uncoupled” from signal transduction pathway, due
to such mechanisms as phosphorylation of the receptor)
Hormone receptors vs. blood binding proteins
- Concentration
Receptor
-low
Blood Binding Protein
-high
Hormone receptors vs. blood binding proteins
- binding affinity
Receptor
-high
Blood Binding Protein
-low
Hormone receptors vs. blood binding proteins
- specificity
Receptor
-high
Blood Binding Protein
-low
Hormone receptors vs. blood binding proteins
saturability at
physiological
concentrations
Receptor
- yes
Blood Binding Protein
- no
Hormone receptors vs. blood binding proteins
reversibility
Receptor
- yes but not as readily
Blood Binding Protein
- yes
Hormone receptors vs. blood binding proteins
signal
transduction
Receptor
- yes
Blood Binding Protein
- no
Endocrine system
Coordinates and integrates the activities of physiological processes in diverse target cells, in response to environmental and internal changes
