The Hypothalamo-Pituitary-Adrenal Axis
Table 10.1 Factors Influencing Evaluation of Endocrine Function in Aging
PhysiologicMetabolism
Body Composition NutritionExercise
Stress
Inter-endocrine RelationsSecretory Rate
Transport to target site
Hormone MetabolismActivity
T4 T3T DHT
Number & Affinity Of Receptors
CNS
↓ GLA ND
↓ TROPIC HORMO NE
↓
GLA ND
↓
BLOO D-HORMO NE
↓ BOUND AND FREE
CIRCULATOR Y
ACTIVE MET ABOLITE
↓
TARGET CELL
↓
RECEPTOR BINDING
TRANSDUCTION
ACTIVATION
↓
RESPONSE
CLEARANCE
Hypophysiotropic hormonesCRH: corticotropic releasing
hormoneGHRH: growth hormone releasing
hormoneGHIH: growth hormone inhibitory
hormone SomatostatinPRH: prolactin releasing hormoneGnRH: gonadotropin releasing
hormoneTRH thyrotropin (TSH)-releasing
hormone
Pituitary HormonesACTH: adrenocorticotropin hormoneLH: lutenizing hormoneFSH: follicle stimulating hormonePL: prolactinTSH: thyroid stimulating hormoneGH: growth hormone
**Please see Figures 10.7-10.9 in text**
Figure 10.1
Vena
Cav
a
Aor
taRightKidney
LeftKidney
Rt.Adrenal
Lf.Adrenal
Figure 10.2
Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and hormones
Capsule
Medulla
Zona GlomerulosaZona Fasciculata
Zona Reticularis
Cortexall layers corticosteronez. fasciculata & reticularis cortisol & sex hormones
z. glomerulosa aldosterone
Medulla epinephrine & norepinephrine
Figure 10-6
C N S
LIMBIC SYSTEM ↓
HYPOTHA LAM US
C R H
↓ PITUITARY
↓ ACTH
↓ ADRENAL CORTEX
↓ GLUCOCORTICOIDS SEX STEROIDS
↓ TARGET CELLS
↓
INTRACELLULAR BINDINGACTIVATION
TRANSLOCATION
↓ MET ABOLIC RESPONSE
CLEARANCE
FREE &BOU ND
(-)
(-)
Reminder
CRH: corticotropicreleasing hormone
ACTH: adrenocorticotropic
hormone
Figure 10.6
Cortiso l
Epinep hrine Nore pinephr ine
Liver
cellular absorption of glucoseglycogenesis
Muscle
celluar absorption of amino acids
White Blood Cells
anti inflammatory action
Brain
excitability (EEG)behavioral changes
Hypothalamus/Anterior Pituitary
negative feedback of CRH, ACTH, GCs
Kidney
Sodium reabsorption (especially by aldosterone)
Bone
bone resorptionosteoporosis
TARGET ACTIONS
Blood Vesselvasoconstrictionvasodilatation
excitation contraction
Intestinerelaxation of motilityconstriction of sphincters of GI tract and bladder
Heart
}Lungs
brochial dilation
Liveractivation of glycogenolysismobilization of metabolicenergy
Adipocytesactivation of lipolysis
Pancreasinhibition of insulin secretion
stimulation of insulin secretion
Brainvigilanceanxiety, fear, ragefunctions of emergency
TARGET ACTIONSActions Of GlucocorticoidsActions of Adrenaline/NoradrenalineTarget
cellular
Figure 10.5 Schematic diagram of corticosteroid action in target cell
mRNA
mRNA
Proteins
BiologicalResponse
Corticosteroid
Intracellularreceptor
Hormone-receptor complex
Hormone-receptorcomplex bound toDNA
Nucleus
•Gene expression & new protein synthesis
•Relatively long latency of onset
•Medium & long term cell program
•Organization of cell networks for complex functions
•Activation/repression of pre-existing cell proteins
•Rapid onset of action
•Rapid adaptation to changes in the milieu
•Dynamic modifications of long term cell programs
GH
ISCHFSHPL
AnteriorPituitary
estrogens
thryroidhormones
androgens
cortico-steroids
LHFSHPL
PL
TSH
ACTH
ovary
mammarygland
thyroid
adrenalcortex
testis
skeleton,muscles,liver
Figure 10.7 Diagrammatic representation of the anterior pituitary
PosteriorPituitary
Oxytocin
Vasopressin
uterine smooth muscle andmammary gland
Kidney function
Figure 10.8 Diagrammatic representation of the posterior pituitary
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
Cortisol, norepinephrine, and epinephrine
STRESS
Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) rats
0 1 2 3 4
0
20
40
Hours
Cor
ticos
tero
neµg
/100
ml
Stress Recovery
young rats
old rats
*
Old ratsYoung rats
Exposure to Stress Generates:
• Specific responses: vary with the stimulus (specialized responses) and generate different responses with each different stimulus.
• Nonspecific responses: (also called non-specialized) are always the same – regardless of the stimulus– mediated through stimulation of neural,
endocrine, and immune axis
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