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Endocrine System II

Endocrine System II. First, Let’s Compare Some General Aspects of the Nervous and Endocrine Systems. Nervous vs. Endocrine Systems. Communication nervous - both electrical and chemical endocrine - only chemical Speed and persistence of response

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Endocrine System II

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  1. Endocrine System II

  2. First, Let’s Compare Some General Aspects of the Nervous and Endocrine Systems

  3. Nervousvs. Endocrine Systems • Communication • nervous - both electrical and chemical • endocrine - only chemical • Speed and persistence of response • nervous - reacts quickly (1 - 10 msec), stops quickly • endocrine - reacts slowly (hormone release in seconds or days), effect may continue for weeks • Adaptation to long-term stimuli • nervous - response declines (adapts quickly) • endocrine - response persists • Area of effect • nervous - targeted and specific (one organ) • endocrine - general, widespread effects (many organs)

  4. What is an Endocrine Axis? This is a Relationship between the hypothalamus, pituitary and a more remote gland…………. There are Three: • Hypothalamic-Pituitary-Gonadal Axis • Hypothalamic-Pituitary-Thyroid Axis • Hypothalamic-Pituitary-Adrenal Axis

  5. REMEMBER the Dry Lab data analysis using stressed mice. There was a control group of mice with a complete HPA. Subsequent groups had variations with missing pieces of this axis. The HPG and HPT axis each work in a similar manner The HPA Axis

  6. General Properties Of Hormones

  7. You Only Need A Small Amount • A Small Amount of Hormone Goes A long Way: ---One molecule activates thousands of enzymes molecules through a process called enzyme amplification

  8. Enzyme Amplification

  9. Hormones are Cleared By The Liver • AND…. Different hormones vary in their rates of clearance. • The rate of hormone removal is called the metabolic removal clearance rate (MCR). • The length of time required to clear 50% of the hormone is from the blood is the half-life. • Each hormone have a specific Half-life which differs due to different molecule structure, weight , whether it is bound or unbound to a transport protein.

  10. Target Cells Modulation of Sensitivity • Target cells can modulate (adjust) their sensitivity to a hormone. • Upregulation- A Cell increases the number of hormone receptors and becomes MORE SENSITIVE to a hormone. • Downregulation- A cell reduces its receptor number and become less receptive to hormone.

  11. Modulation of Target Cell Sensitivity • Long-term use of high pharmacological doses • bind to receptor sites of related hormones • target cell may convert to different hormone

  12. Hormones So Similar In Structure…..

  13. Paradoxical Effects • A target cell can convert one hormone such as testosterone to estrogen, during its pharmacological use. This may have paradoxically, feminization effects!

  14. Hormone Transport • Monoamines and peptides are hydrophilic • mix easily with blood plasma • Steroids and thyroid hormone are hydrophobic • must bind to transport proteins for transport • bound hormone - attached to transport protein, • prolongs half-life to weeks • protects from enzymes and kidney filtration • unbound hormone leaves capillary to reach target cell (half-life a few minutes) • Transport proteins in blood plasma • albumin, thyretin and TGB (thyroxine binding globulin) bind to thyroid hormone • steroid hormones bind to globulins (transcortin) • aldosterone - no transport protein, 20 min. half-life

  15. Mechanism of Hormone Action • Overall: HORMONES influence TARGET CELLS. • They are “ligands” to receptors on cell membranes. • Once bound, hormones alter cell activity by 1. altering plasma membrane potential ( opening ion channels) 2. stimulates synthesis of proteins ..usually regulatory such as enzymes or 3. either activates or deactivates enzymes. 4. Stimulates mitosis.

  16. Some Differences Between Classes • Steroids Hormones- Transported by carriers, as they are hydrophobic, are known to bind to the chromatin (DNA) and initiates transcription. • Protein/Peptide Hormones- Cannot penetrate cell membrane- These use 2nd messenger systems. AND they usually Activate/deactivate enzyme system that are there rather than create more.

  17. Steroid Hormone Action PRESS TO PLAY STEROID HORMONE ANIMATION Figure 9.1a

  18. Nonsteroid Hormone Action PRESS TO PLAY NONSTEROID HORMONE ANIMATION Figure 9.1b

  19. Modulation of Target Cells

  20. Hormone Interactions • Most cells sensitive to more than one hormone and exhibit interactive effects • Synergistic effects • Permissive effects • one hormone enhances response to a second hormone • Antagonistic effects

  21. What Do We Mean BY a Second Messenger? What is the First Messenger? • Hormones the activate 2nd messengers work through a G-Protein. • The hormone bind to a receptor on the membrane (as usual) THIS IS THE 1st messenger. • But the 1st receptor Activates a G-PROTEIN which, in turn, activates the 2nd messenger which is often cAMP

  22. Hydrophilic Hormones: Mode of ActioncAMP as Second Messenger 1) Hormone binding activates G protein 2) Activates adenylate cyclase 3) Produces cAMP 4) Activates kinases 5) Activates enzymes 6) Metabolic reactions: • synthesis • secretion • change membrane potentials

  23. Hydrophilic Hormones: Mode of ActionOther 2nd and 3rd Messengers Hormones may use different second messengers in different tissues.

  24. II. Overview of the Endocrine System • Organs and their hormones • Anatomy and Physiology of Selected Glands • Clinical Implications of Endocrine Malfunctions of Selected Glands

  25. Location of Major Endrocrine Organs Figure 9.3

  26. Do Other Tissues, Besides the Endocrine glands, Secrete Hormones? • Adipose Tissue ( fat) , Stomach , the placenta and there are others secrete hormones but they are not exclusively endocrine glands

  27. Other Organs Not Considered Endocrine Organs, That Secrete Hormones: For Example : Kidneys are not endocrine glands but they produce erthropoietin, a hormone very important in blood formation. They also produce calcitriol ( a form of vitamin D) and renin.

  28. What Are the Hormones For Each Gland? What do they DO?

  29. Let’s Summarize How Endocrine Glands Are Stimulated to Secrete Hormones in the First Place

  30. Going Back a Chapter…..1. Neural Stimuli of Endocrine Glands • Nerve impulses stimulate hormone release • Most are under control of the sympathetic nervous system (Remember the adrenal medulla takes the place of a postganglianic neuron) Figure 9.2c

  31. 2. Control of Hormone Release by Negative Feed back (Rarely Pos.Feedback) • Hormone levels in the blood are maintained by negative feedback • A stimulus or low hormone levels in the blood triggers the release of more hormone • Hormone release stops once an appropriate level in the blood is reached

  32. 3. Hormonal Stimuli of Endocrine Glands ( Tropic Stimuli) • Endocrine glands are activated by other hormones Figure 9.2a

  33. 4. Humoral Stimuli of Endocrine Glands (See Below) • Changing blood levels of certain ions stimulate hormone release Figure 9.2b

  34. Let’s Look at The Glands,Their Function and Control

  35. Part of the brain and connected to the pituitary gland. The hypothalamus maintains heart rate, body temperature, and water balance as well as regulating the activity of the pituitary gland which, in turn, affects the release of hormones. It secretes oxytocin , ADH and releasing factors (regulates the hypophysis) Without this gland the pituitary cannot function properly as it stimulate it. The Hypothalamus

  36. Yellow-brown glands, posterior to thyroid Usually 4 of these Arranged in thick, branching cords containing Oxyphils cells and Chief Cells Oxyphils Cells- larger than chief cells , no hormone produced. No known function. Chief Cells-PTH (Parathyroid Hormone) – This is the single most important hormone controlling the calcium; Stimulates osteoclasts digest some of the bony matrix to release calcium and phosphate into the blood. Parathyroids

  37. Follicular Cells Thyroid Hormone (Thyroxin-T4) and Triidothyronine-T3) T-4 has 4 iodines bound, T3 has 3 iodine bound The main function of T3 and T4 : INCREASING METABOLIC RATE TH also plays a role in providing adrenergic receptors Additionally : is a regulator of growth and development Parafollicular Cell (C-Cells) Calcitonin- This is a polypeptide hormone . Important in lowering blood Calcium and phosphate levels. Most important during childhood when skeleton is growing. Acts on bone, kidney and other cells. Calcitonin controlled via negative feedback with blood concentration. Thyroid Gland(3 Hormones:T3,T4 ,Calcitonin)

  38. Negative Feedback: Thyroid

  39. Goiter- A swollen mass of thyroid tissue/gland resulting from its overstimulation WITHOUT production of viable thyroid hormone. If you have a Thyroid Hormone Deficiency

  40. This time the Thyroid gland is OVERACTIVE and produces too much TH. Person has an elevated metabolic rate, can be nervous, sweaty and losses weight despite great appetite. Often a protrusion of eyes “Betty Davis Eyes”. More common in woman. Treatment: Surgery; Radioactive I destroys some of thyroid cells. Grave’s Disease

  41. Last time We Define A Second Messenger System: Q: Which hormones use second messenger systems? Q: What do we mean by a second messenger system? Q: Which molecule do we ALWAYS find associated with this system? (It facilitates and can be thought of as a “messenger”? Q; What is the first messenger? Q: Can you think of examples of 2nd messengers?

  42. Hydrophilic Hormones: Mode of ActionOther 2nd and 3rd Messengers Hormones may use different second messengers in different tissues.

  43. Adrenal Gland: Cortex • Cortex- OuterPortion, forms the bulk of the gland.. • Arranged in 3 layers: zona glomerulosa, zonafasiculata; and zona retcularis • Produces corticosteroids, synthesized from cholesterol; Subclasses:1. Mineralcorticoids, 2. Glucocorticoids and 3. Gonadocorticoids

  44. Mineral Corticoids • Mineralcorticoids-( mainly ALDOSTERONE) Function: controls sodium retention in kidney tubules; Controls potassium loss in kidney tubules • Control: Angiotensin II , blood concentration controls aldosterone levels.

  45. Glucocorticoids • Include: cortisol (hydrocortisol), cortisone, and corticosterone. • Functions: • 1. Influence energy metabolism by keeping blood sugar levels fairly constant hence the name “gluco’-corticord”. Increases Gluconeogenesis This is when non-carb.s are used to make glucose. Example: amino acids, fats are converted to sugars. • 2. Affect metabolism of all nutrients. • (Next Slide)

  46. Glucocorticoids ( Zona fasiculata) 4. Effects on Inflammation and Immune Function Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases. A long-term consequence of glucocorticoids is that they suppress the immune system. 5.Decrease effect of stress( By helping to adapt to stress --including both physical and psychological) 6. Affect ACTH secretion Control: Corticotropin Releasing Factor (CRF) from hypothalamus. ACTH from adenohypophysis.

  47. Addison's disease is an endocrine or hormonal disorder that occurs in all age groups and afflicts men and women equally. The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and nonexposed parts of the body.( pigment changes result from overstimulation of melanocytes from ACTH ) Addison's disease occurs when the adrenal glands do not produce enough of the hormone cortisol ADDISON’S DISEASE

  48. Cushing’s Disease • This is a HYPERSECRETION Of cortisol. • Usually caused by a tumor on the anterior pituitary gland. • Symptoms: Resemble those of an exaggerated response to stress; • Glucose metabolism is suppressed, whereas lipid reserves are mobilized. The neck and checks use fat reserves, take on a MOONFACE appearance. • Muscle weakness; lack of endurance. Stressed out feeling. • Treatment: remove tumor

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