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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