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 Metabolism Activity
T4 T3
T DHT
Number & Affinity Of Receptors
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
Figure 10.2
Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and hormones
Reminder
CRH: corticotropic releasing hormone
ACTH: adrenocorticotropic
hormone
Figure 10.6
Cortisol
Epinephrine Norepinephrine
Actions Of Glucocorticoids Actions of Adrenaline/Noradrenaline
Target
cellular
Figure 10.5 Schematic diagram of corticosteroid action in target cell
•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
Figure 10.7 Diagrammatic representation of the anterior pituitary
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
Old rats
Young rats
Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) 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