The Hypothalamo-Pituitary- Adrenal 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 ( ).

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 different fields of physiology: Endocrinology Neuroendocrinology Biotechnology ?? Replacement therapy ??

Neuroendocrine Interelations The hypothalamusPituitary Connection with cortex, thalamus, limbic system, reticular formation, etc. Secretes hypophyiotropic hormones Secretes anterior and posterior pituitary hormones

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 in text** Figure 10.1

Reminder CRH: corticotropic releasing hormone ACTH: adrenocorticotropic hormone Figure 10.6

anterior pituitary posterior pituitary adrenal gland kidneyGlucocorticoids

Figure 10.2

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

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 Aging Physiologic Metabolism Body Composition Nutrition Exercise Stress Inter-endocrine Relations Secretory Rate Transport to target site Hormone Metabolism  Activity T 4  T 3 T  DHT 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

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

Cortisol, norepinephrine, and epinephrine STRESS

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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