Pheromones

1. Pheromones Neurotransmitters Other Cellular Regulators- Act like hormones

2. Other Cellular Regulators Besides well recognized kinds of hormone, other substances play important roles as chemical messengers Ca++ Glucose-specific stimuli for insulin secretion from the b cells of the pancreas. Amino acids None of these effectors are not TRADITIONAL hormones, but act like hormones.

3. Besides classics NTs Pheromones Glucose Calcium

4. Control of Endocrine Activity The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial. The concentration of hormone as seen by target cells is determined by three factors: 1.Rate of production: 2.Rate of delivery 3.Rate of degradation and elimination:

5. Control of Endocrine Activity [Hormone] as seen by target cells is determined by 3 factors: Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits. Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow. Rate of degradation and elimination: Hormones have characteristic rates of decay, and are metabolized and excreted from the body via several routes. Shutting off secretion of a hormone that has a very short halflife causes circulating hormone concentration to plummet, but if a hormone's biological halflife is long, effective concentrations persist for some time after secretion ceases.

6. Hormone Synthesis Diversity of hormones structures Lots of interesting pathways of biosynthesis Simplest of hormones-amino acids Glycine and glutamate -act as NTs in brain F and Y-are precursors of dopamine, NE and Epi Which also function as NTs

7. Hormone Synthesis Y also substrate for generation of thyroid hormones W is precursor for serotonin, a CNS NT and melatonin, a pineal hormone

8. Hormone Synthesis Peptide Hormones -translated on secretory pathway (ER..golgi. Sec ves) Made in RER Can have continuous or regulated secretion

9. Hormone Synthesis Steroid Hormones Made within the SER Steroid secreting cells easily recognized by large amounts of SER Complex multiple enzyme system for synthesis secretion

10. Hormone Synthesis Thyroid Hormones Made on protienaceous substrates outside the cell Thyroglobulin Then taken up via endocytosis into the thyroid gland-released from carrier protein prior to secretion from thyroid. UNIQUE PROCESS

11. Hormone Synthesis Prohormones Result from cleavage events after translation Even have preprohormones Examples Renin (enzyme from Kidney) Acts on angiotensinogen (substrate from liver) Results in ANGIOTENSIN I which is converted by another enzyme to Antgiotensin II

12. Hormone Synthesis Prohormones Angiotensin II and bradykins are examples of hormones that are released from liver cells as larger prohormones and converted to active hormone in the blood.

13. Hormone Synthesis NTs Made in axon end of neurons Neuropeptides like oxytocin and vasopressin also made in neurons

14. Hormone Synthesis Summary Variety of processes and intracellular locations involved SER, RER, Cholesterol from inside and outside the cell, Secretory pathway involved in hormone modifications, particulary glycosylation

15. Control of Hormone Secretion Most hormones are made within cells are packaged in secretory vesicles until released Except thyroid and steroid hormones Which are not in secretory vesicles

16. Control of Hormone Secretion Internal and external effectors Extrinsic-light, sounds, smell, temp, Etc. Stimulation of hormone secreting cells results in vesicle fusion with the PM and exocytosis of secretory granules

17. Control of Hormone Secretion Glycos. In Cis Sorting in Trans Golgi

18. Control of Hormone Secretion Hormones often stimulate secretion of hormones from other endocrine glands Pit hormones TSH, FSH, LH and ACTH simulate target tissue cells of thyroid, adrenal, gonads to secrete their own hormones Hormones control other hormones Cascade effect

19. Control of Hormone Secretion Neuroendocrine transduction stimulation of hormone secretion by nerves

20. Control of Hormone Secretion Hormone interaction with some membrane receptors results in membrane depolarization -stimulates movement of Ca++into cells which results in sec. vesicle exocytosis Some chemical messenger inhibit secretion by resulting hyper polarization

21. Hormone Delivery-several routes Endocrine, Para, auto neurocrine- neuron contact target cell and releases hormone neuroendocrine-neuron to blood lumonal-released into lumen of the gut Some delivered by all multiple routes

22. Hormone Circulation and metabolism Peptide hormones have short half lives Exopeptidases and endopeptidases Most steroid hormones bound to plasma proteins. Steroid hormones much more stable

23. Feedback Control of Hormone Production Feedback circuits are at the root of most control mechanisms in physiology, and are particularly prominent in the endocrine system. Instances of positive feedback certainly occur, but negative feedback is much more common.

24. Feedback Control of Hormone Production Negative feedback is seen when the output of a pathway inhibits inputs to the pathway.

25. Feedback loops are used extensively to regulate secretion of hormones An important negative feedback loop is seen in control of thyroid hormone secretion. The thyroid hormones thyroxine and triiodothyronine ("T4 and T3") are synthesized and secreted by thyroid glands and affect metabolism throughout the body.

26. The basic mechanisms for control in this system (illustrated on next slide) are: 1.Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH). 2. TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body. 3.When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. This is an example of "negative feedback".

27. Inhibition of TRH secretion leads to shut-off of TSH secretion, which leads to shut-off of thyroid hormone secretion. As thyroid hormone levels decay below the threshold, negative feedback is relieved, TRH secretion starts again, leading to TSH secretion ... + - + -

28. Target cell response TRH receptors only found in anterior pituitary TSH receptors only found in thyroid gland TH receptors found on every cell Cascade effect + - + -

29. Another type of feedback is seen in endocrine systems that regulate concentrations of blood components such as glucose. Drink a glass of milk or eat a candy bar and the following (simplified) series of events will occur: Glucose from the ingested lactose or sucrose is absorbed in the intestine and the level of glucose in blood rises. Elevation of blood glucose concentration stimulates endocrine cells in the pancreas to release insulin. Insulin has the major effect of facilitating entry of glucose into many cells of the body - as a result, blood glucose levels fall. When the level of blood glucose falls sufficiently, the stimulus for insulin release disappears and insulin is no longer secreted. Numerous other examples of specific endocrine feedback circuits will be presented in the sections on specific hormones or endocrine organs.

30. Hormone Profiles: Concentrations Over Time One important consequence of the feedback controls that govern hormone concentrations and the fact that hormones have a limited lifespan or half-life is that most hormones are secreted in "pulses".The following graph depicts concentrations of luteinizing hormone in the blood of a female dog over a period of 8 hours, with samples collected every 15 minutes:

31. The pulsatile nature of LH secretion in this animal is evident. LH is secreted from the anterior pituitary and critically involved in reproductive function; the frequency and amplitude of pulses are quite different at different stages of the reproductive cycle. With reference to clinical endocrinology, examination of the graph should also demonstrate the caution necessary in interpreting endocrine data based on isolated samples. -

32. A pulsatile pattern of secretion is seen for virtually all hormones, with variations in pulse characteristics that reflect specific physiologic states. In addition to the short-term pulses, longer-term temporal oscillations or endocrine rhythms are also commonly observed and undoubtedly important in both normal and pathologic states.

33. Mechanisms of Hormone Action Immediately after discovery of a new hormone, a majority of effort is devoted to delineating its sites of synthesis and target cells, and in characterizing the myriad of physiologic responses it invokes. An equally important area of study is to determine precisely how the hormone acts to change the physiologic state of its target cells - its mechanism of action.

34. Mechanisms of Hormone Action Understanding mechanism of action is itself a broad task, encompassing structure and function of the receptor, how the bound receptor transduces a signal inside the cell and the end effectors of that signal. This information is not only of great interest to basic science, but critical to understanding and treating diseases of the endocrine system, and in using hormones as drugs.

35. Physiological roles of Hormones What do hormones do???

36. Physiological roles of Hormones Hormones control activity of all cells in the body Affect cellular synthesis and secretion of other hormones After metabolic processes (catabolic and anabolic). Turnover of sugar, proteins and fats Affect Contraction, relaxation and metabolism of Muscle

37. Physiological roles of Hormones Reproduction Cell growth and proliferation Excretion and reabsoroption of ions Affect action of other hormones Role in animal behavior

38. Physiological roles of Hormones Some hormones only exist a few times in the life of an individual hCG Sometimes still have hormone but not sensitive to it any longer Sometimes no longer produce hormone-thyroid hormone, estrogen

39. General mechanisms of Hormone action Receptors Second messengers Phosphorylation involves STY Kinases and phosphatases

40. Reminder aboutGeneral mechanisms of Hormone action Steroid hormones have intracellular receptors. So do Thyroid hormones

41. Endocrine pathophysiology Failure of a gland to secrete enough hormone can lead to fatal consequences No insulin-hyperglycemia-coma and death if untreated

42. General mechanisms of hormone action Hormones regulate specific target tissues NOT ALL CELLS IN the body Determined by?? Receptors-proteins bind hormones Contribute to specificity of action Can be PM or cytosolic or nuclear

43. Hormone response effected by Receptor Levels and hormone levels Oxy and vasopressin AVP have similar structure and both hormones stimulate uterine smooth muscle contraction and activate renal cAMP Uterine receptors more sensitive to OXY Renal receptor more sensitive to AVP Normal hormone conc. Each hormone only activate appropriate cell type

44. Hormone response effected by Receptor Levels and hormone levels When one hormone binds to the receptor of another hormone, this is called CROSS TALK Happens with lots of hormones. If hormone levels are high, will not only act on its own receptor, but similar hormone receptors

45. Some hormones stimulate a number of tissues. Insulin stimulates glucose uptake into skeletal muscle and Fat cells But also talks to liver to shut down output of glucose from liver High Insulin receptor levels on fat, muscle and liver, but low levels in other tissues.

46. Insulin receptors at high levels in skeletal muscle Fat cells LIVER Cells where INSULIN MODULATES glucose metabolism

47. Insulin receptors at low levels in all other tissues where this hormone only has a modest effect on GROWTH DOES NOT MODULATE GLUCOSE METABOLISM IN THESE OTHER TISSUES

48. RECEPTORS FOR A PARTICULAR HORMONE ARE ONLY EXPRESSED IN CELLS WHERE THE HORMONE ACTS. MORE ACTION-MORE RECEPTORS UNDERSTAND INSULIN EXAMPLE (IT IS AN EASY ONE)

49. Hormone response effected by Receptor Levels and hormone levels Have high levels of receptor in tissue that are primary responders

50. Hormones act via own receptors at normal concentrations At high hormone concentrations, hormones can act on similar receptors NE and Epi Oxy and vaso IGF-1 and insulin