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