Lipid-soluble endocrine hormones: Receptors are inside cells. Because they must be synthesized as needed and must generate new proteins to carryout their actions, they represent slow-acting systems. The total plasma level does not necessarily provide an index of activity because most is bound. It is the free hormone that determines activity.
Water-soluble hormones: Receptors are on the membrane surface. Second messengers carry out intracellular action. Because they are stored in vesicles and need only modify proteins to carry out their actions, they are fast-acting systems.
IP3 = inositol trisphosphate
DAG = diacylglycerol
Inside the cell, usually in nucleus
Outer surface of the cell membrane
Stimulates synthesis of specific new proteins
Production of second messengers, e.g., cAMP
Insulin does not utilize cAMP, instead activates membrane-bound tyrosine kinase
Second messengers modify action of intracellular proteins (enzymes)
Synthesized as needed
Exception: thyroid hormones
Stored in vesicles
In some cases, prohormone stored in vesicle along with an enzyme that splits off the active hormone
Attached to proteins that serve as carriers
Exception: adrenal androgens
Dissolved in plasma (free, unbound)
Long (hours, days)
∝ to affinity for protein carrier
Short (minutes)
∝ to molecular weight
A hormone affects only cells that possess receptors specific to that particular hormone.
For example, both adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH) increase the secretion of steroid hormones. However, ACTH does so only in the adrenal cortex and LH only in gonadal tissue.
Under normal conditions, receptors are not saturated; that is, extra receptors exist. Therefore:
Normally, the number of hormone receptors is not rate-limiting for hormone action.
The plasma concentration of free hormone is usually indicative of activity.
Abnormalities in receptors or events distal to the ligand-receptor interaction, often due to chronic elevation of circulating hormone (e.g., type II diabetes) or drug therapy.
Under these conditions receptors are often saturated.
Reduction of hormone levels often produces some recovery in sensitivity.
The clinical presentation is often one of normal or elevated hormone levels but with reduced or absent peripheral manifestations of the hormone and a failure of replacement therapy to correct the problem.
A phenomenon in which one type of hormone must be present before another hormone can act; for example, cortisol must be present for glucagon to carry out gluconeogenesis and prevent hypoglycemia.
Provides information at the time of sampling only and may not reflect the overall secretion rate
When hormone secretion is episodic, single sampling may reflect peaks (erroneous hyperfunction) or nadirs (erroneous hypofunction). Pulsatile secretion, diurnal and cyclic variation, age, sleep entrainment, and hormone antagonism must all be considered in evaluating circulating levels.
Growth hormone is secreted in pulses and mainly at night. This is not reflected in a fasting morning sample. However, growth hormone stimulates the secretion of IGF-I which circulates attached to protein and has a long half-life (20 hours). Plasma IGF-I measured at any time during the day is usually a good index of overall growth hormone secretion.
Thyroid is a fairly constant system and T4 has a half-life of about 6–7 days. Thus, a random measurement of total T4 is usually a good estimate of daily plasma levels.
Restricted to the measurement of catecholamines, steroid hormones, and water-soluble hormones such as hCG and LH.
A distinct advantage of urine analysis is that it provides an integrated sample.
A “24-hour urine free cortisol” is often necessary to pick up a low-level Cushing’s syndrome and to eliminate the highs and lows of the normal circadian rhythm.