The Endocrine System

1. Endocrine and nervous systems work together • Endocrine system • hormones released into the bloodstream travel throughout the body • target is usually far from site of synthesis • binds to receptors on or in target • targets = cells throughout the body • results may take hours, but last longer • Nervous system • certain parts release hormones into blood • rest releases neurotransmitters that excite or inhibit nerve, muscle & gland cells • results in milliseconds, brief duration of effects The Endocrine System

2. Help regulate: • extracellular fluid • metabolism • biological clock • contraction of cardiac & smooth muscle • glandular secretion • some immune functions • Growth & development • Reproduction General Functions of Hormones

3. Exocrine glands • secrete products into ducts which empty into body cavities or body surface • sweat, oil, mucous, & digestive glands • Endocrine glands • secrete products (hormones) into bloodstream • pituitary, thyroid, parathyroid, adrenal, pineal • other organs secrete hormones as a 2nd function • hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart & placenta Endocrine Glands Defined

4. Permissive effect • a second hormone, requires the effects of the first • estrogen & LH are both needed for oocyte production • Synergistic effect • two hormones acting together for greater effect • thyroid strengthens epinephrine’s effect upon lipolysis • Antagonistic effects • two hormones with opposite effects • insulin promotes glycogen formation & glucagon stimulates glycogen breakdown Hormonal Interactions

5. Regulated by signals from nervous system, chemical changes in the blood or by other hormones • Negative feedback control (most common) • decrease/increase in blood level is reversed • Positive feedback control • the change produced by the hormone causes more hormone to be released • Disorders involve either hyposecretion or hypersecretion of a hormone Control of Hormone Secretion

6. Cell Communication: Hormones, Growth factors and Neurotransmitters cells can communicate with those right next to them or can communicate with targets at a distance cell to cell communication can be through gap junctions simplest form of communication OR communication can be through direct contact = adhesion-based mechanisms one cell expresses a receptor, the other expresses the ligand OR through the production of extracellular factors called signals -e.g. hormones, neurotransmitters, neuropeptides, growth factors this is called extracellular signaling

7. Extracellular Signaling in extracellular signaling extracellular signals exert their effects by binding to the target cells and/or entering the cell the ultimate goal is to affect the function of the cell through modifying the expression of genes/proteins

8. Extracellular Signals • there are 3 types of extracellular • signals: • paracrines (e.g. growth factors) • neurotransmitters • endocrines: hormones

9. most signals bind to receptorsthat are specific for that signal most receptors are found on the cell surface although some can be found within the cell binding of the signal (ligand) to the receptor results in a series of events (signal transduction) within the cell that changes the cells function e.g. may change the transcription rate of a gene – effects protein production Extracellular Signaling Mechanisms

10. Cell Communication: Hormones, Growth factors and Neurotransmitters • 6 steps to extracellular signaling: • synthesis of signal (hormone, NT) • release of signal (exocytosis) • transport of signal to target (local? distance?) • detection of signal by target (binding to receptors) • change in target cell function • removal of the signal & loss of effect

11. Hormones: Mechanisms of Signaling hormone producing cell = endocrine cell hormones can use three mechanisms 1. Autocrine signaling 2. Paracrine signaling 3. Endocrine signaling

12. Extracellular Signaling Mechanisms hormones • 1. Autocrine signaling • “self” action • cell responds to the hormone it produces • also used by growth factors

13. Extracellular Signaling Mechanisms hormones • 2. Paracrine signaling • local action • local hormone (paracrine hormone) acts on neighboring cells • autocrines act on same cell that secreted them • used also by growth factors and by neurotransmitters hormones, NTs, growth factors

14. Extracellular Signaling Mechanisms hormones • 3. Endocrine signaling • distant action • circulating hormones (endocrine hormones) act on distant targets • hormones travel in blood

15. Types of Hormones water-soluble lipid -soluble

16. Lipid-soluble Hormones Steroids lipids derived from cholesterol made in SER different functional groups attached to cholesterol core of structure e.g. cortisol, progesterone, estrogen, testosterone, aldosterone Thyroid hormones tyrosine ring plus attached iodines testosterone aldosterone cortisol

17. Lipid-soluble Hormones Retinoic acid lipid derived from retinol (vitamin A) regulates proliferation, differentiation and death of many cell types Vitamin D3 Nitric oxide (NO) Vitamin D3 retinoic acid

18. Eicosanoids prostaglandins or leukotrienes both derived from the fatty acid called arachidonic acid both act in the inflammatory reaction e.g. stimulate smooth muscle cells to contract e.g. stimulate nerve cells – pain Lipid-soluble Hormones

19. synthesis of steroid hormones from cholesterol backbone requires a series of specific enzymatic reactions that modifies the cholesterol these enzymes are specific for each steroid made they are located in specific cell types e.g. enzymes for cortisol are located specifically in the adrenal cortex not stored – once formed they released by diffusion through into the blood only cholesterol is stored in the cytoplasm of the cell Lipid-soluble Hormones

20. lipid-soluble hormones require binding to a carrier protein to be transported in the blood carrier proteins can be specific to the hormone or some can pick up any steroid hormone e.g. serum albumin – indiscriminate in its steroid ‘passenger’ the hormone becomes activated once released at its target therefore the body keeps a balance of bound-inactive steroid hormones and unbound hormones that rapidly enter the cell Lipid-soluble Hormones

21. Action of Lipid-Soluble Hormones: Endogenous signaling Lipid-soluble hormone must be carried by a carrier/transport proteinthat allows it to dissolve within the aqueous environment of the blood plasma Hormone diffuses directly through phospholipid bilayer & into target cell the hormone’s Receptor is located within the cell (cytoplasm or the nucleus)

22. Action of Lipid-Soluble Hormones: Endogenous signaling the site of action for the lipid-soluble H is the nucleus the H and its R binds directly to specific sequences within the DNA = response elements this binding turns on specific genes – activates transcription new mRNA is formed & directs synthesis of new proteins new protein alters cell’s activity

23. Action of Lipid-Soluble Hormones For an animation: http://highered.mcgraw-hill.com/sites/0072943696/student_view0/chapter10/animation__mechanism_of_steroid_hormone_action__quiz_1_.html

24. Action of Lipid-Soluble Hormones some lipid-soluble hormone don’t cross the plasma membrane – too large therefore they bind with receptors on the cell surface and trigger signaling events within the cells signal similar to water-soluble hormones e.g. prostaglandins and leukotrienes

25. Water-soluble Hormones Amine hormones derived from the amino acids tyrosine or tryptophan epinephrine and norepinephrine (tyrosine), serotonin (tryptophan), dopamine (tyrosine) hormones derived from tyrosine are called catecholamines: epinephrine, norepinephrine and dopamine these hormones can also act as neurotransmitters

26. Water-soluble Hormones • Peptide hormones: • comprised of chains of amino acids forming peptides • e.g. growth hormone, oxytocin • Protein hormones: • comprised of one or more polypeptide chains • e.g. insulin hGH oxytocin

27. water-soluble hormones are synthesized and secreted using the same mechanism that regulates the secretion of any other protein made as precursors in the ER transport to the Golgi where they are “pruned” to give rise to the active hormone packaged and secreted from the Golgi stored in the cytoplasm until needed secretion is triggered only by specific stimulus Water-soluble Hormones

28. Water soluble hormones easily travel through the blood - hydrophilic but cannot diffuse through plasma membrane! therefore they require the expression of Receptors on the cell surface Action of Water-Soluble Hormones: The 2nd Messenger System

29. the Receptor protein activates a series of signaling events within the cells common mechanism is G protein signaling e.g. epinephrine binds to Rand activates the adjacent G-protein activated G-protein activates adenylate cyclase ATP is converted to cyclic AMP (cAMP) in the cytosol cAMP acts as a 2nd messenger kinase cascade results gene expression altered Action of Water-Soluble Hormones: The 2nd Messenger System

30. Kinase Cascades

31. Kinase cascades amplify hormone signals

32. Action of Water-Soluble Hormones -http://highered.mcgraw-hill.com/sites/0072943696/student_view0/chapter10/animation__second_messenger__camp.html

33. Both are master endocrine glands since their hormones control other endocrine glands • Hypothalamus is a section of brain above where pituitary gland is suspended from stalk • Hypothalamus receives input from cortex, thalamus, limbic system & internal organs • Hypothalamus controls pituitary gland with7 different releasing & inhibiting hormones Hypothalamus and Pituitary Gland

34. Diencephalon: The Hypothalamus • 1. control of the ANS – integrates signals from the ANS - regulates smooth and cardiac muscle contraction • -major regulator of visceral activities - heart rate, food movements, contraction of bladder • 2. produces hormones & connects with pituitary to regulate its activity • oxytocin • vasopressin

35. 3. regulates emotional and behavioral patterns – rage, aggression, pain and pleasure + sexual arousal 4. regulates eating & drinking – hypothalamus contains a thirst center which responds to a rise in osmotic pressure in the ECF (dehydration) 5. controls body temperature – monitors temp of blood flowing through the hypothalamus

36. Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid • median eminence/infudibulum attaches it to the hypothalamus • Anterior lobe = 75% develops from roof of mouth • comprised of many types of cells for hormone production • Posterior lobe = 25% • ends of axons of 10,000 neurons that originate in hypothalamus • neuroglial cells called pituicytes Pituitary Gland

37. median eminence • portion that marks the connection with the pituitary = median eminence • near the ME are groups of cells = neurosecretory cells • these cells secrete hormones that are either stored in the posterior pituitary or control the anterior pituitary Hypothalamus and Pituitary Gland

38. Hypothalamus and Pituitary Gland • hypothalamic hormones that control the anterior pituitary reach the pituitary via a portal system of capillaries = hypophyseal portal system (HPS)

39. hypothalamus neurosecretory cells secrete two specific hormones that are stored in the posterior pituitary – oxytocin and anti-diuretic hormone (ADH) • these are deposited directly into the posterior pituitary Hypothalamus and the Posterior Pituitary Gland

40. hypothalamic neurosecretory cells also regulate the activity of the anterior pituitary gland through their secretion of specific releasing and inhibiting hormones • e.g. pituitary hormone = somatotropin • hypothalmic hormones = somatotropin releasing hormone (SRH) and somatotropin inhibiting hormone (SIH) Hypothalamus and the Anterior Pituitary Gland

41. Releasing and inhibiting hormones • GHRH/SRH and GHIH/SIH • CRH • PRH and PIH (dopamine) • TRH • GnRH Hypothalamus and the Anterior Pituitary Gland

42. SO: cells of the pituitary releases at least 9 different hormones • BUT it only makes 7 of them

43. neurons in the paraventricular and supraoptic nuclei produce oxytocin and ADH and have axons that travel into the posterior pituitary • stored and eventually released into bloodstream • neurons in the ventral nucleus produce the releasing and inhibiting hormones • travel via the hypophyseal portal system to specific cells of the anterior pituitary • control their action

44. Hormones: human growth hormone- hGH thyroid stimulating - TSH follicle stimulating- FSH leutinizing hormone - LH prolactin adrenocorticotropin - ACTH melanocyte stimulating - MSH • 5 types of cells: • somatotrophs: secrete hGH/somatotropin • thyrotrophs: secrete TSH/thyrotropin • gonadotrophs: secrete FSH, LH • lactotrophs: secrete prolactin • corticotrophs: secrete ACTH/corticotropin & MSH Anterior Pituitary Gland

45. first level of regulation: releasing and inhibiting hormones of the hypothalamus • corticotropin releasing hormone = CRH Anterior Pituitary Gland: Control of Secretion

46. second level is usually negative feedback by hormones released by the target gland • CRH stimulates release of ACTH from corticotroph cells • ACTH travels to the adrenal gland – stimulates production and secretion of cortisol • increase of cortisol makes cortisol act as a CIH/corticotropin inhibiting hormone • increased cortisol levels shut off ACTH production by the corticotroph cells of the pituitary Anterior Pituitary Gland: Control of Secretion

47. Produced by somatotrophs • also known as somatotropin • Hypothalamus: GHRH stimulates somatotroph cells of the pituitary • GHIH (somatostatin) inhibits these cells • Pituitary: hGH release from somatotroph cells • hGH promotes synthesis of insulin-like growth factor-1 (IGF-1) or somatomedin • IGF-1 is made primarily by the liver – also made by skeletal muscle, cartilage and bone cells • common target cells for IGF-1: liver, skeletal muscle, cartilage and bone cells (autocrine action) • increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins Human Growth Hormone (hGH)

48. stimulates lipolysis in adipose so fatty acids can be used for ATP • stimulates release of glucose into the blood by the liver • retards use of glucose for ATP production - so blood glucose levels remain high enough to supply brain • hGH secretion is promoted by decreased fatty acids and amino acids in the blood, decreased blood sugar, deep sleep, increased activity by the sympathetic NS, hormones (glucagon, estrogen, cortisol and insulin) • majority is secreted between the 3rd and 4th NREM sleep stage • adults secrete about 400 ug/day – adolescents about twice that hGH: Other actions

49. Low blood sugar stimulates release of GHRH from hypothalamus • anterior pituitary releases more hGH • hGH stimulates release of IGF-1 • glycogen broken down into glucose by liver cells • increased blood glucose levels • High blood sugar stimulates release of GHIH from hypothalamus • less hGH from anterior pituitary, glycogen does not breakdown into glucose Regulation of hGH

50. Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body) • Excess of human growth hormone • raises blood glucose concentration • pancreas releases insulin continually • beta-cell burnout • Diabetogenic effect: causes diabetes mellitis if no insulin activity can occur eventually • Hypersecretion during childhood = giantism • very tall, normal proportions • Hypersecretion as adult = acromegaly • growth of hands, feet, facial features & thickening of skin Medical application: human growth hormone