The Hypothalamo-Pituitary-Adrenal Axis

MCB 135KApril 7, 2006

Exocrine and Endocrine Secretions

• Cells communicate with each other through three types of chemical messengers

•Neural Communication: neurotransmitter secreted at the synaptic junction

•Endocrine Communication: hormones, secreted into the blood circulation, are carried to the target tissues throughout the body

•Paracrine Communication: products of secretion enter the extracellular fluid to affect neighboring cells

Exocrine and Endocrine Secretions Continued

•Exocrine secretions: the products of secretion are released into a body cavity as for example, the saliva into the mouth, the digestive enzymes into the intestinal cavities

•Autocrine communication: cells secrete chemical messengers that in some situations bind to receptors on the original cells.

Historical Notes• Exocrine secretions were known by Hippocrates and ancient Romans

• The endocrine secretions were first identified at the turn of the 20th century. The first to speak about internal secretions, that is, secretions released into the blood circulations, was the French physiologist CE Brown-Sequard (1817-1894).

Historical Notes Continued

• Brown-Sequard suggested that the internal secretions -- using those of the testes as an example -- influence general metabolism, muscle strength, reproductive and brain function.

• He also suggested that when the internal secretion products were diminished -- as with aging -- some of the functions they regulated were lost.

• But, replacement therapy would restore the lost functions.

In 1905, the internally secreted substances were called “hormones” by the British physiologist E.H. Starling.

The original ideas of Brown-Sequard gave rise to two differentfields of physiology:

EndocrinologyNeuroendocrinology

Biotechnology ??Replacement therapy ??

Neuroendocrine Interelations• The hypothalamus Pituitary

Connection with cortex,thalamus, limbic system,reticular formation, etc.

Secretes hypophyiotropic hormones

Secretes anterior and posteriorpituitary hormones

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

Reminder

CRH: corticotropic releasing hormone

ACTH: adrenocortico

tropic hormone

Figure 10.6

anteriorpituitary

posterior pituitary

adrenalgland

kidney Glucocorticoids

Figure 10.2

Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and

hormones

Cortisol

Epinephrine Norepinephrine

Actions Of Glucocorticoids

Actions of Adrenaline/Noradrenaline Target

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

Table 10.1 Factors Influencing Evaluation of Endocrine

Function in AgingPhysiologicMetabolism

Body Composition NutritionExercise Stress

Inter-endocrine RelationsSecretory Rate

Transport to target site

Hormone Metabolism Activity

T4 T3

T DHT

Number & Affinity Of Receptors

Changes with Aging in the Hypothalamo-

Pituitary-Adrenal AxisNo 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

Old ratsYoung rats

Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) rats

Cortisol, norepinephrine, and epinephrine

STRESS

END

Figure 10.7 Diagrammatic representation of the anterior pituitary

Figure 10.8 Diagrammatic representation of the posterior pituitary

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