The Hypothalamo-Pituitary- Adrenal Axis

Transcription

1 The Hypothalamo-Pituitary- Adrenal Axis

2 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

3 CLEA RA NC E Figure 10.1 CNS GLA ND TROPIC HORMO NE GLA ND BLOO D-HORMO NE BOUND AND FREE IRCULATORC Y ACTIVE MET A BO LITE TA RGET CELL RECEPTOR BINDING TRA NSDUCTION ACTIV A TION RESPONSE 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**

4 Figure 10.2 Rt. Adrenal Aorta Lf. Adrenal Right Kidney Vena Cava Left Kidney

5 Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and hormones Zona Fasciculata Zona Glomerulosa Zona Reticularis Capsule Medulla Cortex all layers corticosterone z. fasciculata & reticularis cortisol & sex hormones z. glomerulosa aldosterone Medulla epinephrine & norepinephrine

6 Figure 10.6 Figure 10-6 C N S LIMBIC SYSTEM HYPOTHA LA M US (-) (-) Reminder CLEA RA NC E CRH: corticotropic releasing hormone ACTH: adrenocorticotropic hormone C R H PITUITARY ACTH ADRENAL CO RTEX GLUCOCORTICOIDS SEX STERO IDS TA RGET CELLS INTRA CELLULA R BINDING ACTIVATION TRANSLOCATION MET A BO LIC RESPONSE FREE & BOU ND

7 Cortiso l Epinep hrine Nore pine phr ine

8 ARGET Liver cellular absorption of glucose glycogenesis Muscle celluar cellular 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 ACTIONS Actions Of Glucocorticoids bone resorption osteoporosis Actions of Adrenaline/Noradrenaline TARGET ACTIONS Target Blood Vessel vasoconstriction vasodilatation Intestine relaxation of motility constriction of sphincters of GI tract and bladder Heart excitation contraction Lungs brochial dilation Liver activation of glycogenolysis mobilization of metabolic energy Adipocytes activation of lipolysis Pancreas inhibition of insulin secretion stimulation of insulin secretion Brain vigilance anxiety, fear, rage functions of emergency }

9 Figure 10.5 Schematic diagram of corticosteroid action in target cell Corticosteroid Intracellular receptor Hormone-receptor complex Biological Response Proteins mrna mrna Hormone-receptor complex bound to DNA Nucleus

10 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 preexisting cell proteins Rapid onset of action Rapid adaptation to changes in the milieu Dynamic modifications of long term cell programs

11 Figure 10.7 Diagrammatic representation of the anterior pituitary estrogens ovary LH FSH PL mammary gland PL thryroid hormones corticosteroids thyroid adrenal cortex skeleton, muscles, liver TSH ACTH GH Anterior Pituitary androgens testis ISCH FSH PL

12 Figure 10.8 Diagrammatic representation of the posterior pituitary Oxytocin Vasopressin uterine smooth muscle and mammary gland Kidney function Posterior Pituitary

13 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

14 STRESS Cortisol, norepinephrine, and epinephrine

15 Figure 10.4 Corticosterone titers in young (3-5 mo) and aged (24-28 mo) rats Corticosterone µg/100 ml * Old rats young rats Young old rats rats 0 Stress Recovery Hours

16 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