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The Hypothalamo-PituitaryAdrenal Axis
MCB 135K
April 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 BrownSequard gave rise to two different
fields of physiology:
Endocrinology
Neuroendocrinology
Biotechnology ??
Replacement therapy ??
Neuroendocrine Interelations
• The hypothalamus
Connection with cortex,
thalamus, limbic system,
reticular formation, etc.
Secretes
hypophyiotropic hormones
Pituitary
Secretes anterior and posterior
pituitary hormones
Figure 10.1
Hypophysiotropic hormones
CRH: corticotropic releasing
hormone
GHRH: growth hormone releasing
hormone
GHIH: growth hormone inhibitory
hormone Somatostatin
PRH: prolactin releasing hormone
GnRH: gonadotropin releasing
hormone
TRH thyrotropin (TSH)-releasing
hormone
Pituitary Hormones
ACTH: adrenocorticotropin hormone
LH: lutenizing hormone
FSH: follicle stimulating hormone
PL: prolactin
TSH: thyroid stimulating hormone
GH: growth hormone
**Please see Figures 10.7-10.9 in text**
Figure 10.6
Reminder
CRH: corticotropic
releasing hormone
ACTH:
adrenocorticotropic
hormone
anterior
pituitary
posterior
pituitary
adrenal
gland
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
•Activation/repression of preexisting cell proteins
•Relatively long latency of onset
•Rapid onset of action
•Medium & long term cell
program
•Rapid adaptation to changes in
the milieu
•Organization of cell networks
for complex functions
•Dynamic modifications of long
term cell programs
Table 10.1 Factors Influencing Evaluation of
Endocrine Function in Aging
Physiologic
Metabolism
Body Composition
Nutrition
Exercise
Stress
Hormone Metabolism
 Activity
T4  T3
T  DHT
Inter-endocrine Relations
Secretory Rate
Transport to target site
Number & Affinity
Of Receptors
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
Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) rats
Old rats
Young rats
STRESS
Cortisol, norepinephrine, and epinephrine
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 nonspecialized) are always the same
– regardless of the stimulus
– mediated through stimulation of neural,
endocrine, and immune axis