Assessment of Endocrine Function Flashcards
What is the endocrine system composed of?
Classical Endocrine glands (e.g. pituitary, adrenal, parathyroid, etc.)
Clusters of hormone-secreting cells located throughout the body in tissues that are not normally considered to be endocrine glands
What is the concentration of a hormone in the blood dependent on?
Rate of secretion
Rate of degradation
Describe hormone degradation
Hormones are typically degraded at a constant rate, and therefore not responsible for normal fluctuations in circulating levels
Important factor in determining speed at which a hormone signal decays
How is hormone degradation measured?
Plasma half-life (T1/2) - expressed in units of time
Metabolic Clearance Rate (MCR) - expressed in terms of the volume of plasma cleared per unit time. Represents sum of all processes involved in the removal of a hormone
What is the basal rate of secretion?
Endocrine glands have a basal rate of secretion when unstimulated
What factors affect the rate of hormone secretion?
Rate of synthesis
Release of stored hormones
Size and number of secretory cells
What are the patterns of hormone release?
Diurnal - higher or lower depending on time of day
Pulsatile - regular pattern that increases and decreases
Episodic - in response to stimuli
What types of stimuli cause endocrine glands to secrete hormones?
Neuronal Stimulation
Other hormones
Metabolites
Local mediators (paracrine signaling)
What is the two-site immunometric assay?
Immunoassaay commonly used to measure hormone concentrations
Uses two antibodies, one is labeled and one is bound to a solid surface to extract the hormone from the mixture
What are bioassays?
Used to determine what fraction of the circulating hormone pool is biologically active
E.g. receptor-binding assay, assay measuring generation of second messenger
What is a provocative test?
Test that stimulates or suppresses the release of the hormone in question
What are stimulation tests?
Commonly used when an endocrine gland is thought to be hypofunctional
Substances used include: Exogenous hormones, physiological stimuli, metabolic blocking agents that provoke production
What are suppression tests?
Commonly used when an endocrine gland is thought to be hyperfunctional
Assess the functional status of the negative feedback system
What can binding studies be used to determine?
Total number of receptors per unit mass of tissue
Affinity of the receptor for the hormone
What is the dissociation constant?
Equivalent to the concentration of hormone required for half of the receptors to be occupied
The lower the Kd, the greater the affinity for binding
What conditions alter receptor affinity (Ka)?
Covalent modification of a receptor
Allosteric interactions when the hormone binds with its receptor
pH or ionic composition of the environment
Inherited receptor mutations
What conditions affect circulating hormone levels [H]?
Endogenous signals
Dysfunctional endocrine glands
What conditions affect the receptor content of tissues [Rt]?
Altered rate of receptor synthesis
Altered rate of receptor degradation
Compartmentalization of receptor
What is a concentration-response curve?
Plot of the magnitude of an effect induced by a hormone as a function of the concentration of that hormone
Typically sigmoidal in shape
What is threshold?
Minimum concentration of hormone required to produce a detectable response
What is sensitivity?
The ability of a target cell to recognize and respond to a hormone in proportion to the intensity of the signal
Typically expressed in terms of the concentration of hormone that produces a half-maximal response
What is maximum response?
The effect produced by a saturating concentration of hormone
How will the concentration-response curve be shifted if sensitivity is increased? Decreased?
Increased - shifts left
Decreased - shifts right
What factors can decrease the sensitivity of a receptor?
Decrease in the affinity of the receptor
Increase in the rate of hormone degradation
Increase in the concentration of an antagonist hormone
Administration of a competitive antagonist
How will the concentration-response curve change under conditions that diminish the capacity of a target tissue to respond?
Cause a decrease in the maximum response
What conditions diminish the maximum response to a hormone?
Reduction in the amount of target tissue
Decrease in the concentration of a critical enzyme
Decrease in available substrate
Administration of a non-competitive antagonist
What are spare receptors?
In some tissues, the maximum response for a given effect is reached when only a fraction of the receptors are occupied
These extra receptors are spare receptors, and the greatly enhance the sensitivity of the cell to the hormone
May also play a role in hormone degradation
