1. POWERPOINT ® LECTURE SLIDE PRESENTATION by LYNN CIALDELLA, MA, MBA, The University of Texas at Austin Additional material by J Padilla for Physiology 31 at ECC Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings HUMAN PHYSIOLOGY AN INTEGRATED APPROACH FOURTH EDITION DEE UNGLAUB SILVERTHORN UNIT 4 23 Endocrine Control of Growth and Metabolism

2. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings About this Chapter  Adrenal glucocorticoids  Thyroid hormones  Growth hormone  Tissue and bone growth  Calcium balance

3. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Adrenal Glucocorticoids Structure and function of the adrenal gland Figure 23-1a

4. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-3 Cortisol The HPA pathway for the control of cortisol secretion CRH- Corticotrophic Releasing Hormone ACTH- Adrenocorticotrophic hormone Cortisol- lipophilic hormone that enters the nucleus and althers gene expression, transcription, and translation

5. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cortisol Cortisol receptors are found in every tissue in the body and release varies throughout the day.

6. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cortisol  Promotes gluconeogenesis- stimulates the liver to increase blood glucose levels  Causes breakdown of skeletal muscle proteins – releases amino acids to act as substrates for gluconeogenesis  Enhances lipolysis- releases glycerol for gluconeogenesis and fatty acids for cellular respiration  Suppresses the immune system- reduces inflammation and other immune system functions. When used as a medication (ibuprofen) it need to be taper off once not needed.  Causes negative calcium balance - reduces absorption and increases bone matrix breakdown  Influences brain function – affect mood, memory, and learning.

7. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cortisol: Therapeutic Drug  Suppresses the immune system – prevents cytokine & antibody production, helps prevent organ rejection,  Inhibits the inflammatory response – reduced the mobility of leukocytes  Used to treat:  Bee stings, poison ivy, and pollen allergies  Prevents rejection of transplanted organs

8. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-5 Hypercortisolism Adrenal tumor that autonomously secretes cortisol- primary hypercortisolism Pituitary tumor that autonomously secretes ACTH (adrenocorticotropic hormone)- secondary hypercortisolism Cushing’s disease- hyperglycemia, muscle breakdown, lipolysis, extra fat in trunk and face, Iatrogenic hypercortisolism- resulting from cortisol therapy (exogenous cause) Adrenal tumor that autonomously secretes cortisol- primary hypercortisolism Pituitary tumor that autonomously secretes ACTH (adrenocorticotropic hormone)- secondary hypercortisolism Cushing’s disease- hyperglycemia, muscle breakdown, lipolysis, extra fat in trunk and face, Iatrogenic hypercortisolism- resulting from cortisol therapy (exogenous cause) Individual with Cushing’s Syndrome cause by adrenal or pituitary tumor

9. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Hypocortisolism  Less common than Cushing’s syndrome  Addison’s disease- hereditary defects in enzymes needed to make the steroid hormones  Hyposecretion of all adrenal steroid hormones  Autoimmune destruction of adrenal cortex

10. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings CRH Family  CRH (corticotropin-releasing hormone) – is involved in the following:  Inflammation and immune response  Decreases food intake  Signals that mark onset of labor  Linked to anxiety, depression, and other mood disorders  Urocortin: brain neuropeptide related to CRH

11. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings ACTH and Melanocortins  ACTH- secretion stimulated by CRH  Synthesized from POMC (pro-opiomelanocortin)  POMC products include  -endorphin- an opiate that blocks pain  Processed in tissue outside the pituitary- produces different molecules  Additional processing creates  -MSH- it inhibits food intake in brain and acts on melanocytes in skin  Melanocortins  Family name for the MSH (melanocyte-stimulating hormone) hormones and ACTH **there are five melanocortin receptors in the adrenal gland and skin cells (melanocytes)

12. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Thyroid: Structure Figure 23-7a

13. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-8 Thyroid Thyroid hormones are made from iodine and tyrosine- they are thermogenic so they increase O 2 for oxydative phosphorylation. Thyroid hormones synthesis takes place in the colloid of the thyroid follicle

14. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-12 Pathway of Thyroid Hormone Control Negative feedback mediated by thyroid hormones reaches the hypothalamus to stop production at the pituitary. In thyroid disorders negative feedback is removed Negative feedback mediated by thyroid hormones reaches the hypothalamus to stop production at the pituitary. In thyroid disorders negative feedback is removed

15. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Hyperthyroidism  Affects: metabolism, the nervous system, & the heart  Increases oxygen consumption and metabolic heat production – patients have a high metabolism and since they generate a lot of heat they don’t tolerate hot environments well.  Increase protein catabolism and may cause muscle weakness – the body breaks down the protein in muscle cells which also causes weight loss.  Hyperexcitable reflexes and psychological disturbances – may affect the nervous tissue structure and receptors.  Influence  -adrenergic receptors in the heart - increases heart rate and contraction force

16. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-15 Thyroid Exophthalmus, caused by hypertrophy of tissues in the eye socket, is a sign of hyperthyroidism

17. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Hypothyroidism  Slow metabolic rate and oxygen consumption – less tolerant to cold because they don’t generate much internal heat due to lower metabolic rate.  Decreases protein synthesis – causing brittle nails, thinning hair, dry thin skin, and myxedema. In children it retards growth.  Slowed reflexes, slow speech and thought processes, and feelings of fatigue – nervous response is slower or less efficient  Cretinism in infants- decreased mental capacity  Bradycardia – slower heart rate

18. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-13 Thyroid A man with goiter due to excessive TSH stimulation – immunoglobulins released in hyperthyroidism mimic TSH and stimulate thyroid enlargement (Grave’s Disease) may also be caused by excess thyroid- stimulation in hypothyroidism

19. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-14a Thyroid Goiter can occur in both hyperthyroidism and hypothyroidism

20. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Normal Growth  Growth hormone and other hormones - GH, thyroid hormones, insulin, and sex hormones at puberty are important for normal growth and development.  An adequate diet – sufficient calories, protein, vitamins and minerals provide the building blocks for proper growth.  Absence of stress – stressful environments cause children to release cortisol which stunts growth  Genetics – height potential is inherited

21. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-16 Pathway of Growth Hormone Control Growth hormone promotes anabolism of proteins. It is released by anterior pituitary and IGF provides negative feedback cycles. GH is bound to a binding protein to keep it from being excreted in urine and to increase its lifetime.

22. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Growth Hormone In adults, pulses of GH are released during the first two hours of sleep. The greatest amount of GH release occurs during puberty.

23. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Growth Hormone  Severe GH deficiency leads to dwarfism  Oversecretion of GH in children leads to giantism  Oversecretion of GH in adults leads to acromegaly

24. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Tissue and Bone Growth  Growth is determined by increase in soft tissue (weight) and bone length (height)  Tissue growth requires hormones and paracrines  GH and IGFs required for protein and cell division for hypertrophy and hyperplasia  Thyroid hormone plays permissive role- directly affects nervous system development  Insulin supports tissue growth- stimulates protein synthesis and provides energy, has a permissive role  Bone growth requires adequate dietary calcium  Hydroxyapatite- most common form of calcium **review parts of a long bone as covered in anatomy

25. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-18 Bone Growth Compact and trabecular bone Bone length increases at the epiphyseal plate and diameter with matrix deposits around surface

26. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-19 Bone growth Linear growth of long bones takes place at the epiphyseal plates- sex hormones eventually inactivate epilhyseal plates. Epiphysis is the end of a long bone. Diaphysis is the shaft of a long bone. Epiphyseal plate is the site of bone growth. Diaphysis Compact bone Osteoblast Direction of growth Chondrocyte Cartilage owth Newly calcified bone Bonegr Dividing chondrocytes add length to bone. Chondrocytes produce cartilage. Old chondrocytes disintegrate. Osteoblasts lay down bone on top of cartilage.

27. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Calcium  Important signal molecule – increased Ca 2+ concentrations allows for cell responses like exocytosis and muscle contraction. Active transport is needed to decrease cytosolic Ca 2+ concentration.  Part of intercellular cement that holds cells together at tight junction – integrated component of the cell junction protein structure  Cofactor in the coagulation cascade – The body will always have enough calcium to mediate coagulation  Affects the excitability of neurons – hypocalcemia causes the NS to become hyperexcitable, thus increasing muscle contraction. Hypercalcemia cause NS to be hypoexcitable causing depressed neuromuscular activity.

28. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-20 (2 of 5) Calcium Balance in the Body [free Ca 2+ ] 0.001 mM Active transport Cells [Ca 2+ ] 2.5 mM ECF Electrochemical gradient PTH = parathyroid hormone KEY Calcium in the ECF is either bound to proteins or free to diffuse. Calcium in ICF is stored in mitochondria, or ER, or free in cytosol Calcium in the ECF is either bound to proteins or free to diffuse. Calcium in ICF is stored in mitochondria, or ER, or free in cytosol

29. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-20 (3 of 5) Calcium Balance in the Body [free Ca 2+ ] 0.001 mM Active transport Cells [Ca 2+ ] 2.5 mM Calcitonin Ca 2+ PTH Calcitriol Cortisol Bone ECF Electrochemical gradient PTH = parathyroid hormone KEY Bone is largest calcium reservoir. It is stored as hydroxyapartite crystals. Calcium is released to maintain plasma levels

30. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-20 (4 of 5) Calcium Balance in the Body Ca 2+ Small intestine Dietary calcium [free Ca 2+ ] 0.001 mM Calcitrol (PTH, prolactin) Active transport Cells [Ca 2+ ] 2.5 mM Calcitonin Ca 2+ PTH Calcitriol Cortisol Bone ECF Electrochemical gradient PTH = parathyroid hormone KEY Only 1/3 of the calcium ingested is absorbed. Absorption is regulated by a hormone. A healthy diet needs to be high in calcium in order to match the amount excreted

31. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-20 (5 of 5) Calcium Balance in the Body Total body calcium = intake  output Ca 2+ Small intestine Dietary calcium Calcium in feces [free Ca 2+ ] 0.001 mM Kidney Ca 2+ in urine Ca 2+ in kidney tubules Calcitrol (PTH, prolactin) Active transport Some calcium is secreted into the small intestine. Cells [Ca 2+ ] 2.5 mM Passive filtration Calcitonin Ca 2+ PTH Calcitonin PTH Calcitriol Cortisol Bone ECF Electrochemical gradient PTH = parathyroid hormone KEY Calcium is mostly excreted by the kidneys through urine and a small amount is lost in feces. Calcium reabsorption at the kidneys is regulated by hormones or transport proteins

32. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-21 Calcium Balance Osteoclasts are responsible for bone resorption – a low pH environment and proteases are needed to dissolve bone matrix.

33. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Calcium Balance  Parathyroid hormone: increases plasma Ca. concentration by stimulating its release/reabsorption from bone, kidney, and intestine.  Mobilizes calcium from bone- does not bind osteoclast but promotes release of paracrines the increse its activity  Enhances renal reabsorption- prevents excessive build up of calcium in urine  Indirectly increases intestinal absorption- used calcitrol to increase absorption  Calcitriol – vitamin D3, most important in adults, acts bone, liver, intestine  Calcitonin- targets osteoclasts and reduces bone resorption, thus dropping blood ]Ca 2+ ]

34. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-22 Calcium Balance: Parathyroid Glands

35. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Calcium Balance

36. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-23 Endocrine Control of Calcium Balance

37. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Calcium Balance  Calcium and phosphate homeostasis are linked- most phosphate in the body is found in bone, it is processed similarly in the same three organs that process calcium by the same hormones.  Phosphate is key ingredient of hydroxyapatite  Phosphate has other roles  Energy transfer and storage  Activation and deactivation of enzymes, transports, and ion channels  Part of DNA and RNA backbone

38. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 23-24 Osteoporosis Normal bone (left) and bone loss in osteoporosis (right)