PLASMA CONCENTRATION OF
HORMONES
Dr. Amel Eassawi
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OBJECTIVES
The Student Should be able to:
 Explain the factors that influence the plasma concentrations of
hormones.
 Recognizing the different types of hormone interactions and the
significance of hormone concentrations.
 Explain the principles of positive and negative feedback control of
hormone secretion.
 Explain the effects of secretion, excretion, degradation, and volume of
distribution on the concentration of a hormone in blood plasma.
 List hormone measurements assays.
 Identifying the most common causes of endocrine dysfunctions.
PLASMA CONCENTRATION OF
HORMONE
The effective plasma concentration of a hormone
depends on:
1. The rate of secretion into the blood by the endocrine gland.
2. The rate of metabolic activation or conversion. Example: T4 to T3
or conversion of small amount of testosterone to estrogen.
3. The extent of binding to plasma proteins (lipophilic hormones).
Example during pregnancy the level of thyroid hormone is high
even with normal thyroid function.
4. The rate of removal from the blood by metabolic inactivation and
excretion in the urine.
The effective plasma concentration of a hormone is normally regulated by
changes in the rate of its secretion.
CONTROL OF HORMONE
SECRETION
Rate of secretion of hormone depends on:
1. Negative feed back control
2. Neuroendocrine reflexes
3. Circadian and Diurnal Rhythm
Negative Feedback Control:
Negative feedback exists when the output of a system counteracts a
change in input, maintaining a controlled variable within a narrow
range around a set level.
Neuroendocrine Reflex:
Sudden increase in hormone secretion in response to a specific
stimulus. Control system involve both neural and endocrine factor. Example
secretion of epinephrine is controlled by sympathetic nervous system.
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CONTROL OF HORMONE
SECRETION
1. Diurnal Rhythm
Day–night Example increase Prolactin secretion during night.
2. Circadian Rhythm
circadian (“around a day”) rhythm, which is characterized by
repetitive oscillations in hormone levels that are very regular and
cycle once every 24 hours. Example Cortisol
3. Sleep Wake Rhythm
Example Infants / Children increase GH during sleep
increase ACTH and Cortisol during sleep
4. Infradian Rhythm
Ovarian steroids – Estrogen & Progesterone
5. Developmental Rhythm
Example Growth Rhythm
6. Ultradian Rhythm
-moment to moment change Example insulin
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CONTROL OF HORMONE SECRETION
Feedback Loops
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CIRCADIAN RHYTHM
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CIRCADIAN RHYTHM
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CIRCADIAN/DIURNAL PATTERNS AND
THE LIFE CYCLE
Steiger et al., . (J Int Med. 254: 13-22, 2003)
Luboshitzky et al., (J. Clinical Endocrinol Metab. 88:
3160-3166, 2003)
Right panel: Arrows indicate 1st onset of REM sleep.
ULTRADIAN OSCILLATIONS
INFRADIAN RHYTHM
Adapted from Santoro et al, (Journal of Clinical Endocrinology and Metabolism, 81: 1495–1501, 1996)
NEUROENDOCRINE REFLEX
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REGULATION OF HORMONE
RECEPTORS
Down Regulation:
A mechanism in which a hormone decreases the number or affinity
of its receptors in a target tissue. Down-regulation may occur by
decreasing the synthesis of new receptors, by increasing the
degradation of existing receptors, or by inactivating receptors.
Up Regulation:
A mechanism in which a hormone increases the number or affinity
of its receptors. Up-regulation may occur by increasing synthesis of
new receptors, decreasing degradation of existing receptors, or
activating receptors.
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RESPONSIVENESS OF TARGET CELL TO
HORMONE
HORMONE CLEARANCE FROM BLOOD
The rate of removal of the hormone from the blood which is called the
metabolic clearance rate
occurs by:
– metabolic destruction by the tissues.
– binding with the tissues.
– excretion by the liver into the bile.
– excretion by the kidneys into the urine.
HORMONE CLEARANCE FROM BLOOD
Lipophilic hormones are bound to plasma proteins so free
hormone available is less to the tissues
Rate of Removal of Hormone:
Hydrophilic hormones are easily inactivated by blood and tissue enzyme.
Remains in blood for (few minutes to few hours)
Lipophilic hormones are found in a bound form in the blood. They are
less susceptible to enzymatic inactivation. Hormones remain in blood for
larger time few hours (steroids) and weeks (thyroid hormone).
Patients with liver & kidney disease may suffer from excess of hormone
activity.
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HORMONE MEASUREMENT
• Bioassay
• Chemical assay
• Immunoassay – important for diagnosis of
endocrine-related diseases, determining
metabolic clearance rate and pattern of
hormone secretion.
SYNERGISTIC EFFECTS OF
HORMONES
PERMISSIVENESS, SYNERGISM, AND
ANTAGONISM
Permissiveness:
one hormone must be present in adequate amounts for the full
exertion of another hormone’s effect. thyroid hormone increases the
number of receptors for epinephrine in epinephrine’s target cells.
Synergism:
occurs when the actions of several hormones are complementary
and their combined effect is greater than the sum of their separate
effects
Presence of FSH & Testosterone for effective spermatogenesis.
Antagonism:
occurs when one hormone causes the loss of another hormone’s
receptors, reducing the effectiveness of the second hormone
Progesterone (a hormone secreted during pregnancy that decreases
contractions of the uterus) inhibits uterine responsiveness to
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estrogen.
ENDOCRINE DISEASES
•
•
•
•
Hormone Overproduction
Hormone Underproduction
Altered Tissue Responses
Tumors of Endocrine Glands
HYPOSECRETION
• Primary hyposecretion: occurs when an endocrine gland is
secreting too little of its hormone because of an abnormality within
that gland
• Secondary hyposecretion: takes place when an endocrine gland
is normal but is secreting too little hormone because of a deficiency
of its tropic hormone.
Primary hyposecretion:
genetic (inborn absence of an enzyme that catalyzes synthesis of the
hormone, such as the inability to synthesize cortisol because of the lack
of a specific enzyme in the adrenal cortex.
HYPOSECRETION
• Dietary (lack of iodine, which is needed for synthesis of thyroid hormone).
• Chemical or toxic (certain insecticide residues may destroy the adrenal
cortex).
• Immunologic (autoimmune antibodies may destroy the body’s own
thyroid tissue).
• Other disease processes (cancer or tuberculosis may coincidentally
destroy endocrine glands).
• Iatrogenic (physician induced, such as surgical removal of a cancerous
thyroid gland).
• Idiopathic (meaning the cause is not known).
HYPERSECRETION
• Primary hypersecretion
– When the defect lies within the gland itself
• Secondary hypersecretion
– Results from excessive stimulation from the outside
• Tumor
• Immunological defect - excessive stimulation of the thyroid
gland by an abnormal antibody that mimics the action of
TSH, the thyroid tropic hormone.
• Substance abuse - athletes of using certain steroids that
increase muscle mass by promoting protein synthesis in
muscle cells
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Table 18-1, p. 665
REFERENCES
 Human physiology, Lauralee Sherwood, seventh
edition.
 Text book physiology by Guyton &Hall,11th
edition.
 Physiology by Berne and Levy, sixth edition.