1. Diabetes mellitus  Normal blood glucose levels = 80 to 120 mg/100 ml of blood  When not absorbed to rises, spills into urine  Glucose is expelled, water follows leading to dehydration  Not using glucose, fats and proteins used Loss of weight and issue with infections Blood becomes acidic (acidosis) due to ketones in blood (ketosis)  Two types Type II – adult onset, Insulin resistant, insulin produce, cells don’t recognize. Treated with diet and drugs to help with insulin sensitivity Type I – juvenile, no insulin made. Treated with pump or injections

2. Pineal Gland  In brain, function not completely understood  Melatonin – sleep trigger Peak levels at night, make sleepy Lowest levels at noon Secretion highest age 1-5, 75% smaller in adolescence Helps regulate mating behaviors in animals Humans coordinates hormones of fertility ○ Inhibits reproductive system – inhibits gonadotropins

3. Thymus Gland  Upper thorax, posterior to sternum  Thymosin and thymopoietin Normal development of T cells, lymphocytes Decreases in size throughout life, mostly fibrous connective and fat by old age. What effect on immune system?

4. Gonads  Sex hormones same as adrenal cortex  Ovaries – Ova (exocrine) Estrogen – sex characteristics of women Progesterone and estrogen – breast development and menstrual cycle  Testes – Sperm (exocrine) Testosterone – sex characteristic of men, voice, muscle, sex drive, continuing sperm production

5. Ovaries  Each follicle contains egg with Granulosa cells  Granulosa cells secrete estrogen called estradiol ½ of menstrual cycle, copus lutem secretes estradiol and progesterone after ovulation and 8-12wks of pregnancy Reproductive system development Feminine physique, Bone growth Regulate menstrual cycle Sustain pregnancy  Follicle and corpus luteum secrete inhibin suppresses FSH via neg feedback

6. Testes  Interstitial cells secrete testosterone and other androgens Male reproductive system Male physique Sex drive Sperm production and sexual instinct all life  Sustentacular cells secrete inhibin Inhibits FSH, regulates sperm production

7. Diseases associated with the Thyroid Gland Figure 9.8 Goiter Figure 9.9 Grave’s Disease exophthalmos Hyperthyroidism – rapid heartbeat, high metabolism, agitated, hard to relax, thyroid gland enlarges, eyes bulge. Treated with surgery, or drugs. Hypothyroidism – results in myxedema, physically and metally sluggish, puffy, dry skin, obese, low temp. Treated with Thyroxine

8. Addison’s Disease  Hyperpigmentation  Bronze coloring of skin  Aldosterone is low, water and Na lost, electrolyte problems  Muscle weakness

9. Hormone Chemistry  Most are either Steroid hormone – derived from cholesterol ○ Sex steroids, corticosteroids, Calcitriol (not steroid but derived from one) Peptide hormones – chains of 3-200+ aa ○ Hormones from Post Pit, most releasing and stimulating hormones from Hypothalamus, most hormones from Ant Pit Monoamines – chain of aa and amino group ○ epinephrine, NE, dopamine, melatonin, and TH

10. Hormone Synthesis -Steroids  All made from either cholesterol or AA  Steroids Synthesized from cholesterol, functional group attached to 4 ring structure differs

11. Hormone Synthesis - Peptides  Gene transcribed to mRNA, mRNA translated into preprohormones  Small chain of AA direct preprohormone to ER, snipped off = prohormone, inactive  Off to the Golgi for modification and packaging

12. Hormone Synthesis - Monoamines  From AA that retain amino group Melatonin from Tryptophan, others from Tyrosine TH unique- TH comes from a larger protein called Thyroglobulin, not part of finished TH ○ TH two tyrosine linked together ○ TH requires Iodine

13. Synthesis of TH  1) ______ cells secrete thyroglobulin into lumen of follicle = colloid  2) I absorbed by follicular cells from blood, transported into lumen  3) I added to tyrosine of thyroglobulin = monoiodotyrosine (MIT)  4) Another I added, diiodotyrosine (DIT)  5) DIT + either MIT or DIT  6) DIT + MIT = T3, DIT + DIT = T4 but both still connected to Thyroglobulin  7) TSH stimulated follicular cells to take up colloid by pinocytosis, lysosome fuses, cleaves off thyroglobulin  Get 10%T3 and 90%T4

14. Hormone Transport  Transport via blood, hydrophilic Peptides and monoamines are good, hydrophilic as well What about Steroids? ○ Need transport proteins – albumins and globulins from liver Bound vs. Unbound ○ Transport ○ Prolongs ½ life TH over 99% bound, removal of Thyroid, TH up to 2 weeks Aldosterone - ½ life twenty minutes

15. Figure 9.1 Mode of Action  Direct Gene Activation – lipid soluble, steroids and thyroid hormone  Second-Messenger System – water soluble, nonsteroidal Different cellular responses to same hormone

16. Thyroid Hormone Specifically  Carried by transport TBG, dissociates in blood  T3 and T4 enter cytoplasm  T4 – I cleaved ->T3 Mitochondria – stimulate aerobic respiration Ribosomes – incr. mRNA translation Receptors on chromatin, incr. gene transcription ○ Sodium potassium pump

17. Peptides and Catecholamines  Hydrophilic  Two second messenger systems  cAMP and Diacylglycerol and Inositol Triphosphate (IP3)

18. Enzyme Amplification  Hormones only needed in small amounts to get effect in cell needed due to cascade  1 glucagon molecule trigger production of 1000 cAMP  1 cAMP makes 1 kinase  1 kinase activates 1000 enzyme molecules  Each enzyme activates 1000 end product  1 glucagon produced 1 billion end molecules

19. Hormone Clearance  Most cleared by liver and kidneys, excreted in bile or urine  Some degraded by target cells  Bound take longer to clear than unbound  Metabolic clearance rate (MCR) = rate hormone cleared  Higher MCR shorter ½ life

20. Modulation of Cell Sensitivity  Up-regulation – target cell increases receptors for hormone to make itself more sensitive Uterus and OT for labor  Down-regulation – reduction in receptors so target less sensitive to hormones, Happens when long exposure to high hormone levels ○ Cells of testis down regulate in response to high lutenizing hormone What happens with long term hormone treatments?

21. Hormone interactions  Lots of different hormones in blood and cells sensitive to more than one hormone  Cells have to have specific receptor to be sensitive to a hormone  Interactions Synergistic – 2+ hormones work together = FSH and testosterone inc sperm #’s Permissive – one hormone enhances a targets response to a later hormone ○ Estrogen stim up-regulation of progesterone receptors in uterus Antagonistic – oppose actions ○ Insulin and glucagon ○ Calcitonin and Calcitriol