Assessment of Endocrine Function

Question 1

What is the endocrine system composed of?

Answer 1

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

Question 2

What is the concentration of a hormone in the blood dependent on?

Answer 2

Rate of secretion

Rate of degradation

Question 3

Describe hormone degradation

Answer 3

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

Question 4

How is hormone degradation measured?

Answer 4

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

Question 5

What is the basal rate of secretion?

Answer 5

Endocrine glands have a basal rate of secretion when unstimulated

Question 6

What factors affect the rate of hormone secretion?

Answer 6

Rate of synthesis

Release of stored hormones

Size and number of secretory cells

Question 7

What are the patterns of hormone release?

Answer 7

Diurnal - higher or lower depending on time of day

Pulsatile - regular pattern that increases and decreases

Episodic - in response to stimuli

Question 8

What types of stimuli cause endocrine glands to secrete hormones?

Answer 8

Neuronal Stimulation

Other hormones

Metabolites

Local mediators (paracrine signaling)

Question 9

What is the two-site immunometric assay?

Answer 9

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

Question 10

What are bioassays?

Answer 10

Used to determine what fraction of the circulating hormone pool is biologically active

E.g. receptor-binding assay, assay measuring generation of second messenger

Question 11

What is a provocative test?

Answer 11

Test that stimulates or suppresses the release of the hormone in question

Question 12

What are stimulation tests?

Answer 12

Commonly used when an endocrine gland is thought to be hypofunctional

Substances used include: Exogenous hormones, physiological stimuli, metabolic blocking agents that provoke production

Question 13

What are suppression tests?

Answer 13

Commonly used when an endocrine gland is thought to be hyperfunctional

Assess the functional status of the negative feedback system

Question 14

What can binding studies be used to determine?

Answer 14

Total number of receptors per unit mass of tissue

Affinity of the receptor for the hormone

Question 15

What is the dissociation constant?

Answer 15

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

Question 16

What conditions alter receptor affinity (Ka)?

Answer 16

Covalent modification of a receptor

Allosteric interactions when the hormone binds with its receptor

pH or ionic composition of the environment

Inherited receptor mutations

Question 17

What conditions affect circulating hormone levels [H]?

Answer 17

Endogenous signals

Dysfunctional endocrine glands

Question 18

What conditions affect the receptor content of tissues [Rt]?

Answer 18

Altered rate of receptor synthesis

Altered rate of receptor degradation

Compartmentalization of receptor

Question 19

What is a concentration-response curve?

Answer 19

Plot of the magnitude of an effect induced by a hormone as a function of the concentration of that hormone

Typically sigmoidal in shape

Question 20

What is threshold?

Answer 20

Minimum concentration of hormone required to produce a detectable response

Question 21

What is sensitivity?

Answer 21

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

Question 22

What is maximum response?

Answer 22

The effect produced by a saturating concentration of hormone

Question 23

How will the concentration-response curve be shifted if sensitivity is increased? Decreased?

Answer 23

Increased - shifts left

Decreased - shifts right

Question 24

What factors can decrease the sensitivity of a receptor?

Answer 24

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

Question 25

How will the concentration-response curve change under conditions that diminish the capacity of a target tissue to respond?

Answer 25

Cause a decrease in the maximum response

Question 26

What conditions diminish the maximum response to a hormone?

Answer 26

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

Question 27

What are spare receptors?

Answer 27

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