Download glucocorticoids

Section 6 Adrenal Gland
Adrenal Cortex Anatomy
Divided into three regions:
• zona glomerulosa
- secretes aldosterone
• zona fasciculata
- secretes glucocorticoids
• zona reticularis
- secretes androgens
Adrenal Cortex: Steroid Hormone
Production
I. Adrenal Cortical Hormones
The mineralocorticoids are secreted by
zona glomerulosa
Essential for life.
Promotes sodium retention and Potassium
elimination by the kidney.
Expands ECF volume
Aldosterone is the principal
mineralocorticoid.
The glucocorticoids are secreted by both
zona fasciculata and zona reticularis,
exhibiting an important effect on increasing
blood glucose concentration.
Cortisol is the principal glucocorticoid.
Small amounts of sex hormones are secreted
by the zona reticularis.
1. Biological Effects of Adrenocortical Hormones
(1)On metabolism
1) On carbohydrate metabolism.
A Stimulation of gluconeogenesis by the liver
through two pathways.
B Reduction of glucose utilization by the cells.
Cortisol decrease the rate of glucose
utilization by the cells everywhere in the
body because of inhibition of response of
cells to insulin.
Elevate blood glucose concentration
2) On protein metabolism
A. Cortisol mobilizes amino acids from the
nonhepatic tissues and diminishes the tissue
stores of protein and increase amino acids
uptake by the liver for gluconeogenesis.
B. Cortisol decreases protein synthesis in
body cells except those of the liver and
increases catabolism of protein in many
extrahepatic tissues especially in muscle and
lymphoid tissue.
3) On fat metabolism
A. Cortisol promote mobilization of fatty acids
from adipose tissue which increases the
concentration of free acids in the plasma
B. Increases oxidation of fatty acids in the liver
cells for energy.
Cushing’ s Syndrome
Many people with excess
cortisol secretion develop
a peculiar type of obesity,
with excess deposition of
fat in the chest and head
regions of the body,
giving a buffalo-like torso
and a rounded face, a
“moon-face”.
Biochemical & clinical concepts
of Cushing`s syndrome
Biochemical Changes
Clinical Effects
Increased gluconeogenesis
Hyperglycemia (may be DM)
Disturbed fat metabolism with
redistribution
Truncal obesity (Buffalo hump)
Severe catabolic effects on proteins
Thinning of skin
Wasting of muscles
Osteoporosis of bones
Suppressed immune response
Poor wound healing
Reduced resistance to infection (low
immunity)
Mineralocorticoid effects of cortisol
Hpernatremia (increased Na+ in blood)
Hypokalemia (decreased K+ in blood)
Alkalosis
Hypertension
Cushing’s Syndrome
“moon
face”
striae
(2) Effects on water and electrolytes
Cortisol has a slight effect on enhancement of
sodium reabsorption and potassium excretion by
distal tubules and colleting ducts in kidney.
It increases the rate of renal blood flow and
then glomerular filtration rates, facilitating water
excretion.
In patients with adrenal insufficiency, excretion of
water is so slow that there is a danger of water
intoxication and only glococorticoids can repair this
deficit.
(3) On blood cells
Cortisol increase the production of red cells
and platelets by stimulating bone marrow.
Cortisol decrease the number of
lymphocytes and eosinocytes because it
causes atrophy of the all lymphoid tissues and
promotion of destruction of lymphocytes and
eosinocytes.
(4) On cardiovascular system
Glucocorticoids are necessary for maintenance
of normal blood pressure. There are three
mechanisms at least.
1) Cause permissive action, enhancing the response
of vascular muscle to catecholamines.
2) Inhibit synthesis of prostaglandins that have
vasodilator effect.
3) Reduces the permeability of capillaries, which is
useful to maintenance of blood volume.
(5) Effect on stress.
Trauma，surgery，infection，intense cold or
heat，nervousness and anxiety，can cause an
immediate and great increase in ACTH secretion
by the anterior pituitary gland，followed by
marked increase of adrenocortical secretion，
mainly cortisol in human. This is called the stress
response.
This increase is essential for survival.
(6) Other effects.
Glucocorticoids also have many other effects
such as:
increase in production of HCl and pepsin,
promotion of synthesis of fetal surfactant.
Glucocorticoids have pharmacological effects
including anti-inflammatory, antiallergic and
antishock effect.
2. Regulation of Secretion of Adrenocortical
Hormone
Hypothalamus – Anterior
Pituitary – Adrenocortical Axis
(1)Action of ACTH:
Cortisol secretion is almost
entirely controlled by ACTH
(adrenocorticotropin hormone)
ACTH causes formation of
adrenocortical hormones by
increasing cAMP as a second
messenger and activates steps for
controlling adrenocortical secretion.
Long-term stimulation of the
adrenal cortex by ACTH not only
increases secretory activity but also
causes hypertrophy and
proliferation of the adrenocorticol
cells, especially in the zona
fasciculata and zona reticularis,
where cortisol and androgens are
secreted.
(2) CRH (corticotropin releasing
hormone)
A, Action of CRH
The action of CRH is to promote
synthesis and release of ACTH in
the cells of anterior pituitary gland.
B, Regulation of CRH secretion
a. CRH is secreted in irregular
bursts throughout the day and
plasma ACTH and cortisol tends to
rise and fall in response to these
bursts.
Fluctuations in plasma ACTH and glucotorticoids
throughout the day in a normal girl (age 16).
b. Any type of stress can
lead to enhance secretion
of CRH through afferent
nerve pathways on
hypothalamus.
c. CRH secretion is
inhibited by cortisol via a
feedback mechanism
(3) Feedback
mechanism
Cortisol has direct
negative feedbacks on
the hypothalamus to
decrease formation of
CRH
High circulating levels
of cortisol inhibit
secretion and
formation of ACTH,
decreasing response
of anterior pituitary
gland to CRH.
High levels of ACTH
also inhibit CRH
secretion by a
negative feedback
mechanism.
These feedbacks help
regulate the plasma
concentration of
cortisol toward a
normal control level.
Acts very much like a part of the
sympathetic nervous system (fight or flight)
Secretes two amines:
 norepinephrine (20%)
 epinephrine (80%)
Stimulated by preganglionic neurons directly,
so controlled by the hypothalamus as if
part of the autonomic nervous system,
NOT by tropic hormones
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1.cardiovascular effects
epinephrine or norepinephrine +β1-R→HR↑;
myocardial contractility↑;vasodilation of coronary
vessels→cardiac output↑
norepinephrine+α-R(vessels)→vasoconstriction
epinephrine +α-R(vessels)→vasoconstriction
epinephrine +β2-R→vasodilation

2.metabolic effects
glycogenolysis↑, lipolysis↑, heat
production↑, oxygen consumption↑
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3.other effects:
inhibiting the releasing of insulin,
increasing excitability of CNS

Emergency reaction
Medulla
 The adrenal medulla mediates
short–term responses by secreting
catecholamine hormones.
 Cells are modified neurons (lack
axons)
• Epinephrine (adrenaline)
• Norepinephrine (noreadrenaline)
– enable a rapid ( fight-or-flight )
responses to stress by
increasing blood glucose and
blood pressure and directing
blood to the heart, brain, and
skeletal muscles.
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