Download The Hypothalamo-Pituitary- Adrenal Axis

The Hypothalamo-PituitaryAdrenal Axis
Table 10.1 Factors Influencing Evaluation of
Endocrine Function in Aging
Physiologic
Metabolism
Body Composition
Nutrition
Exercise
Stress
Hormone Metabolism
ÇÈ Activity
T4 Î T3
T Î DHT
Inter-endocrine Relations
Secretory Rate
Transport to target site
Number & Affinity
Of Receptors
CNS
Figure 10.1
↓
GLA N D
↓
TROPIC HORMO N E
↓
CLEA RA NC E
GLA N D
↓
BLOO D -HORMO N E
↓
BO UN D A N D FREE
IRCULA
C
TOR Y
A CTIV E MET A BO LITE
↓
TA RGET CELL
↓
RECEPTOR BIN D IN G
TRA NS D UCTION
A CTIV A TION
↓
RESPO NS E
Hypophysiotropic hormones
CRH: corticotropic releasing
hormone
GHRH: growth hormone releasing
hormone
GHIH: growth hormone inhibitory
hormone Somatostatin
PRH: prolactin releasing hormone
GnRH: gonadotropin releasing
hormone
TRH thyrotropin (TSH)-releasing
hormone
Pituitary Hormones
ACTH: adrenocorticotropin hormone
LH: lutenizing hormone
FSH: follicle stimulating hormone
PL: prolactin
TSH: thyroid stimulating hormone
GH: growth hormone
**Please see Figures 10.7-10.9 in text**
Aorta
Figure 10.2
Right
Kidney
Vena Cava
Rt.
Adrenal
Lf.
Adrenal
Left
Kidney
Figure 10.3 Diagram of a section of the adrenals illustrating the
various zones and hormones
Zona Fasciculata
Zona Glomerulosa
Zona Reticularis
Capsule
Medulla
Cortex
all layers
z. fasciculata & reticularis
z. glomerulosa
Medulla
corticosterone
cortisol & sex hormones
aldosterone
epinephrine & norepinephrine
Figure 10-6
Figure 10.6
C N S
LIMBI
C SYSTEM
↓
(-)
(-)
HYPO THA LA M US
CRH
↓
PITUITA RY
↓
CLEA RA NC E
A CTH
↓
A D REN A L CO RTEX
Reminder
CRH: corticotropic
releasing hormone
ACTH:
adrenocorticotropic
hormone
↓
GLUCO CO RTICO ID S
EX
S STERO ID S
↓
TA RGET CELLS
↓
IN TRA CELLULA R BIN D IN G
A CTIV A TIO N
TRA NS LO CA TIO N
↓
MET A BO LIC RESPO NS E
FREE &
BOU N D
Cortiso l
Epinep hrine
Nore pine phr ine
TARGET
ACTIONS
Actions
Of Glucocorticoids
Liver
cellular absorption of glucose
glycogenesis
Muscle
cellular
celluar
absorption of amino acids
Actions
of Adrenaline/Noradrenaline
TARGET
ACTIONS
Target
Blood Vessel
vasoconstriction
vasodilatation
Intestine
relaxation of motility
constriction of sphincters of
GI tract and bladder
Heart
White Blood Cells
anti inflammatory action
Brain
excitability (EEG)
behavioral changes
Hypothalamus/Anterior Pituitary
negative feedback of CRH, ACTH, GCs
excitation
contraction
}
Lungs
brochial dilation
Liver
activation of glycogenolysis
mobilization of metabolic
energy
Adipocytes
activation of lipolysis
Kidney
Sodium reabsorption (especially by
aldosterone)
Bone
bone resorption
osteoporosis
Pancreas
inhibition of insulin secretion
stimulation of insulin secretion
Brain
vigilance
anxiety, fear, rage
functions of emergency
Figure 10.5 Schematic diagram of corticosteroid action in target cell
Corticosteroid
Hormone-receptor
complex
Intracellular
receptor
Biological
Response
Proteins
mRNA
Hormone-receptor
complex bound to
DNA
mRNA
Nucleus
•Gene expression & new protein
synthesis
•Activation/repression of preexisting cell proteins
•Relatively long latency of onset
•Rapid onset of action
•Medium & long term cell
program
•Rapid adaptation to changes in
the milieu
•Organization of cell networks
for complex functions
•Dynamic modifications of long
term cell programs
Figure 10.7 Diagrammatic
representation of the anterior pituitary
estrogens
thryroid
hormones
corticosteroids
androgens
ovary
LH
FSH
PL
mammary
gland
PL
thyroid
TSH
adrenal
cortex
ACTH
skeleton,
muscles,
liver
GH
testis
ISCH
FSH
PL
Anterior
Pituitary
Figure 10.8 Diagrammatic
representation of the posterior
pituitary
Posterior
Pituitary
Oxytocin
uterine smooth
muscle and
mammary gland
Vasopressin
Kidney function
Changes with Aging in the
Hypothalamo-Pituitary-Adrenal Axis
No significant changes in healthy, non-stressed, elderly
The few changes that occur are rapidly compensated for
(e.g. decreased secretion of GCs from the adrenal cortex)
but also
less rapid metabolism in the liver & less urine excretion
Therefore the circulating levels remain constant
Also, normal ACTH & cortisol responses to CRH administration
Some alterations of the circadian rhythm
STRESS
Cortisol, norepinephrine, and epinephrine
Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) rats
40
Corticosterone µg/100 ml
Old
youngrats
rats
old rats rats
Young
20
*
0
Stress
0
Recovery
1
2
Hours
3
4
Exposure to Stress Generates:
• Specific responses: vary with the stimulus
(specialized responses) and generate different
responses with each different stimulus.
• Nonspecific responses: (also called nonspecialized) are always the same
– regardless of the stimulus
– mediated through stimulation of neural,
endocrine, and immune axis