Endocrine new.ppt
- 2. The Endocrine System Hormones are conventionally defined as organic substances, produced in small amounts by specific tissues (endocrine glands), secreted into the blood stream to control the metabolic and biological activities in the target cells. Hormones may be regarded as the chemical messengers involved in the transmission of information from one tissue to another and from cell to cell. The major endocrine organs in human body are depicted in fig:
- 3. Endocrine system maintains homeostasis The concept that hormones acting on distant target cells to maintain the stability of the internal milieu is a major advance in physiological & biochemical understanding. The secretion of the hormone is evoked by a change in the milieu and the resulting action on the target cell restores the milieu to normal; leading to the maintenance of homeostasis
- 4. Sensing and signaling Endocrine “glands” synthesize and store hormones. These glands have a sensing and signaling system which regulate the duration and magnitude of hormone release via feedback from the target cell.
- 5. Endocrine vs. Nervous System • Major communication systems in the body • Integrate stimuli and responses to changes in external and internal environment • Both are crucial to coordinated functions of highly differentiated cells, tissues and organs • Unlike the nervous system, the endocrine system is anatomically discontinuous.
- 6. •The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast. •The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extra cellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.
- 7. A cell is a target because it has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone.
- 8. Number of Receptors • Down-regulation: is the decrease of hormone receptors which decreases the sensitivity to that hormone • Up-regulation: is the increase in the number of receptors which causes the cell to be more sensitive to a particular hormone
- 9. Functions of Endocrine System • Controls the processes involved in movement and physiological / biochemical equilibrium • Includes all tissues or glands that secrete hormones into the blood • Secretion of most hormones is regulated by a negative feedback system • The number of receptors for a specific hormone can be altered to meet the body’s demand • Maintenance of the internal environment in the body (maintaining the optimum biochemical environment). • Integration and regulation of growth and development. • Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth, development and nourishment of the newborn.
- 10. Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.
- 11. Response vs. distance traveled Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it.
- 12. Major hormones and systems • Top down organization of endocrine system. • Hypothalamus produces releasing factors that stimulate production of anterior pituitary hormone which act on peripheral endocrine gland to stimulate release of third hormone – Specific examples to follow • Posterior pituitary hormones are synthesized in neuronal cell bodies in the hypothalamus and are released via synapses in posterior pituitary. – Oxytocin and antidiuretic hormone (ADH)
- 13. Range from 3 amino acids to hundreds of amino acids in size. Often produced as larger molecular weight precursors that are proteolytically cleaved to the active form of the hormone. Peptide/protein hormones are water soluble. Comprise the largest number of hormones– perhaps in thousands Peptide/protein hormones
- 14. • Are encoded by a specific gene which is transcribed into mRNA and translated into a protein precursor called a preprohormone • Preprohormones are often post-translationally modified in the ER to contain carbohydrates (glycosylation) • Preprohormones contain signal peptides (hydrophobic amino acids) which targets them to the golgi where signal sequence is removed to form prohormone • Prohormone is processed into active hormone and packaged into secretory vessicles
- 15. • Secretory vesicles move to plasma membrane where they await a signal. Then they are exocytosed and secreted into blood stream • In some cases the prohormone is secreted and converted in the extracellular fluid into the active hormone: an example is angiotensin is secreted by liver and converted into active form by enzymes secreted by kidney and lung
- 17. Chemical Classification of Hormones • Steroid Hormones: – Lipid soluble – Diffuse through cell membranes The Endocrine organs include: • Adrenal cortex • Ovaries • Testes • placenta
- 18. • Nonsteroid Hormones: – Not lipid soluble – Received by receptors external to the cell membrane These include: – Peptides and proteins – Amino acid derivatives – Fatty acid derivatives - Eicosanoids The Endocrine organs include • Thyroid gland • Parathyroid gland • Adrenal medulla • Pituitary gland • pancreas
- 19. Chemical diversity of hormones
- 20. Classification based on mechanism of action Group I. Hormones that bind to intracellular receptors Hormones Origin Major Functions
- 21. Group II. Hormones that bind to cell surface receptors A. The second messenger is cAMP Hormones Origin Major Functions
- 22. Hormones Origin Major Functions Grp. II. B. The Second Messenger is Phosphatidyl Inositol / Calcium Group II. C. The Second Messenger is cGMP Atrial natriuretic cardiac diuresis, vasodilation, ms. relaxation factor (ANF) atrial tissue inhibition of aldosterone secretion Nitric oxide (NO) arginine vasodilation, smooth ms.relaxation, regulation of BP, neurotransmitter
- 23. Hormones Origin Major Functions Group II. D. The Second Messenger is Kinase/phosphatase or unknown / Unsettled
- 24. General features of hormone classes
- 25. Hormone Actions • “Lock and Key” approach: describes the interaction between the hormone and its specific receptor. – Receptors for non-steroid hormones are located on the cell membrane – Receptors for steroid hormones are found in the cell’s cytoplasm or in its nucleus
- 26. • Steroid Hormones – Pass through the cell membrane – Binds to specific receptors – Then enters the nucleus to bind with the cells DNA which then activates certain genes (Direct gene activation). – mRNA is synthesized in the nucleus and enters the cytoplasm and promotes protein synthesis for: • Enzymes as catalysts • Tissue growth and repair • Regulate enzyme function
- 27. Mechanism of action of steroid hormones
- 28. • Non-steroid Hormones – React with specific receptors outside the cell – This triggers an enzyme reaction with lead to the formation of a second messenger (cAMP). – cAMP can produce specific intracellular functions: • Activates cell enzymes • Change in membrane permeability • Promote protein synthesis • Change in cell metabolism • Stimulation of cell secretions
- 29. cAMP in glycogenolysis (phosphorylation)
- 30. cAMP in glycogen synthesis (glycogenesis) Dephosphorylation Similar action of cGMP from GTP
- 31. cAMP in Lipolysis + promoting effect - inhibiting effect
- 32. Synthesis and degradation of cAMP
- 33. G. Proteins: Types & Functions
- 34. The Endocrine Systems • The Pituitary Gland is divided into 2 areas, which differ – structurally and functionally – each area has separate types of hormone production. – Anterior Pituitary: • produces thyroid- stimulating hormone (TSH) • growth hormone (GH) • adrenocorticotropin (ACTH) • follicle-stimulating hormone (FSH) • Leutinizing (LH) • Prolactin (PRL) – The two segments are: • Posterior Pituitary: – produces oxytocin and antidiuretic hormone (ADH)
- 35. Overview of pituitary gland
- 37. • Pituitary Gland – A marble-sized gland at the base of the brain – Controlled by the hypothalamus or other neural mechanisms and therefore the middle man. • Posterior Lobe – Antidiuretic hormone: responsible for fluid retention – Oxytocin: contraction of the uterus Oxytocin ADH
- 38. Comparison between ADH & Insulin deficiency Diabetes Diabetes Mellitus Diabetes Inspidus Mellitus means sweet inspidus means tasteless. Insulin deficiency ADH deficiency Polyuria moderate polyuria severe Urine sp. gravity↑ specific gravity↓ Hyperglycemia Blood glucose normal Urine benedict test +ve Benedict test negative
- 39. Exercise appears to be a strong stimulant to the hypothalamus for the release of all anterior pituitary hormones. Hypothalamic hormones: TRH, CRH, GnRH, GRH, GRIH, PRIH • Pituitary Gland • Master Endocrine Gland (Chairman) • ADENOHYPOPHYSIS: catagorized as • GH-PROLACTIN GROUP: growth hormone, Prolactin • GLYCOPROTIN HORMONES: TSH, LH, FSH, HCG? • POMC PEPTIDE FAMILY : ACTH, LPH?, endorphin?
- 40. Main actions of ACTH Effects on adrenal cortex :- i. Increases synthesis and release of adrenocorticoids ii. Increases adrenal cortical growth (trophic effect). iii. ↑production leads to ↑glucose & cushing syndrome. iv. Lowers contents of vit.C of adrenal cortex. v. Lowers cholesterol of adrenal cortex. Extra adrenal effects of ACTH:- i. Release of free fatty acids from fats. ii. Slight diabetogenic action. iii. Release of insulin. iv. Decreased deamination of amino acids. v. Liberation of histamine. vi. Pigmentation of the skin.
- 41. Main actions of Growth Hormone Protein synthesis Hyperglycemia Lipolysis ↑rate of growth Retention of Ca, P, Mg, Na, K, CI. Growth Hormone disorders 1. Panhypopitutarism:↓GH, ↓growth →dawarfism. 2. Hyperpituitarism with excessive GH production: a) Gigantism (before puberty) b) Acromegaly (in adult age)
- 42. Pro-opiomelanocortin (POMC) family members ACTH-Adrenocorticotropic Hormone LPH-Lipotropin, MSH-Melanocyte stimulating hormone CLIP-Corticotropin like intermediate lobe peptide
- 43. Amine hormones There are two groups of hormones derived from the amino acid tyrosine Thyroid hormones and Catecholamines
- 44. • Two other amino acids are used for synthesis of hormones: • Tryptophan is the precursor to serotonin and the pineal hormone melatonin • Glutamic acid is converted to histamine
- 45. • The Thyroid Gland – lies in the anterior neck just below the larynyx. – Two lobes, located on either side of the trachea, connected by a narrow band of tissue called the isthmus. – Sacs inside the gland contain colloid • Within the colloid are the thyroid hormones: – thyroxine (T4) – triiodothyronine (T3) • When stimulated (by TSH or by cold), these are released into the circulatory system and the metabolic rate. – “C” cells within the thyroid produce the hormone calcitonin.
- 46. Structures of Thyroid Hormones
- 47. Thyroid Hormone Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms. Thyroid hormone is produced by the thyroid gland and is lipid soluble Thyroid hormones are produced by modification of a tyrosine residue contained in thyroglobulin, post- translationally modified to bind iodine, then proteolytically cleaved and released as T4 and T3. T3 and T4 then bind to thyroxin binding globulin for transport in the blood
- 48. Biosynthesis of Thyroid Hormones
- 50. Overview of Regulation & functions of Thyroid Hormones
- 51. • Thyroid Gland – Located along the midline of the neck – Secretes two nonsteroid hormones • Triiodothyronine (T3) • Thyroxine (T4) – Regulates metabolism • increases protein synthesis • promotes glycolysis, gluconeogenesis, glucose uptake • Calcitonin: calcium metabolism • when released, lowers the amount of calcium in the blood.
- 52. • Disorders of hypothyroidism. In infants Cretinism: Growth & mental retardation. In adults Myxedema: Low BMR, sensitivity to cold, slow heart rate,, slowing of all intellectual functions, dry skin & hair, hypercholesterolemia, sluggish behaviour.
- 53. • Increased thyroid hormone release causes hyperthyroidism, commonly called Graves’ disease. – Signs and symptoms: • insomnia, fatigue • tachycardia • hypertension • heat intolerance • weight loss • ↑BMR, moist skin • Fine tremors • ↓B.Wt, hypocholesteremia – Long term hyperthyroidism: • Exopthalmos – bulging of the eyeballs (picture Barbara Bush) – ↑LATS/TSI, – ↑T3 & T4 • In severe cases - a medical emergency called thyrotoxicosis can result.
- 54. • Parathyroid Glands – small, pea-shaped glands, located in the neck near the thyroid – usually 4 - number can vary – Regulate the level of calcium in the body – Regulates phosphate levels – produce parathyroid hormone (PTH) - level of calcium in blood by osteoclast activity through cAMP – Hypocalcemia can result if parathyroids are removed or destroyed.
- 55. • Adrenal Glands – 2 small glands that sit atop both kidneys. – Each has 2 divisions, each with different functions. – Catecholamines: • Epinephrine: elicits a fight or flight response • Increase H.R. and B.P. • Increase respiration • Increase metabolic rate • Increase glycogenolysis • Lipolysis • Vasoconstriction • Dilation of bronchioles • Norepinephrine House keeping system A. The Adrenal Medulla secretes the catecholamine hormones norepinephrine and epinephrine (closely related to the sympathetic component of the autonomic nervous system). B. Adrenal cortex secrets Adrenocorticosteroids
- 56. Catecholamine hormones Catecholamines are both neurohormones and neurotransmitters. These include epinephrine, and norepinephrine Epinephrine and norepinephrine are produced by the adrenal medulla both are water soluble Secreted like peptide hormones
- 59. • Essential role of adrenaline in emergencies Increases body capabilities in stressful conditions : Raises blood glucose for energy (glycogenolysis). Increases FFA level for energy (lipolysis) ↑cardiac output, ↑BP, ↑ blood supply to muscle. ↑breathing capacity; ↑ rate and depth of respiration. Contract spleen to add more RBCs to circulation.
- 60. • Pheochromocytoma It is tumor of adrenal medulla causing hypersecretion of catecholamines. It is diagnosed by - Signs-symptoms : palpitation, tremors, headache etc. Raised BP. (hypertension: paroxysmal or persistent). Raised glucose hyperglycemia and glycosuria. Raised levels of plasma catecholamines ↑Urine excretion of VMA and catecholamines
- 61. Pancreas Gland – a key gland located in the folds of the duodenum – has both endocrine and exocrine functions – secretes several key digestive enzymes • Islets of Langerhans – specialized tissues in which the endocrine functions of the pancreas occurs • include 3 types of cells: • alpha ( ) • beta () • delta () • f- Cells • each secretes an important hormone.
- 62. • Alpha () cells release glucagon, essential for controlling blood glucose levels. • When blood glucose levels fall, cells the amount of glucagon in the blood . • The surge of glucagon stimulates the liver to release glucose stores (from glycogen and additional storage sites). • Also, glucagon stimulates the liver to manufacture glucose by gluconeogenesis.
- 63. • Beta Cells () release insulin (antagonistic to glucagon). • Insulin the rate at which various body cells take up glucose. Thus, insulin lowers the blood glucose level (Hypoglycemic). • Insulin is rapidly broken down by the liver by insulinase and must be secreted constantly. • Delta Cells () produce somatostatin, which inhibits both glucagon and insulin. • f- Cells-- Polypeptide
- 64. Main actions of insulin and glucagon Insulin Glucaqon a) Anabolic catabolic b) Hypoglycemic hyperglycemic c) Glycogenesis glycogenolysis d) ↓Gluconeogenesis ↑gluconeogenesis e) ↑ GIycolysis ↓glycolysis f) Protein synthesis proteolysis g) Lipogenesis lipolysis h) ↓Ketogenesis ↑ketogenesis i) Nucleic acid synthesis urea synthesis.
- 65. Human proinsulin, insulin & C-peptide
- 66. Mechanism of insulin action IRS= Insulin receptor substrate
- 67. insulin-dependent tissues for glucose metabolism Adipose tissue, Skeletal muscle, Liver. Liver cells require insulin for glucose metabolism not for glucose transport through cells. insulin-independent tissues for glucose uptake Brain, liver, RBCs, WBCs, intestinal mucosa, cornea, lens of eyes & renal tubules. The word NSILA stands Non-suppressible insulin like activity (somatomedin).
- 68. Glucose Homeostasis Blood Glucose Fastin 70-100 mg/dl Post-prandial 110-126mg/dl
- 69. Comparison B/W types of D.M
- 70. • Main complaints of a diabetic person In early stage of disease: Polyuria, polydipsia, polyphagia. In late stage patient develops: body pains, weight loss, generalized weakness, neuropathy (burning feet), nephropathy (albuminuria), retinopathy and cataract in early age. • Common tests for diabetes mellitus Routine laboratory tests for diagnosis for DM. are :- a) Urine test for sugar: +ve from green to red ppt. b) Fasting blood glucose : >140 mg/dl confirms DM. c) Random or 2 hrs glucose: >200 mg/dl confirms DM. d) GTT is done to confirm if above tests are disputed. e) HbA 1c estimation for DM management
- 71. Oral GTT
- 72. Glycosuria& its causes. Glycos-sweet, uria-urine. It means presence of sugar in urine. Normally sugar is not present in urine. Causes are: a) Diabetes mellitus b) Renal glycosuria (renal threshold) c) Alimentary d) In pregnancy e) Emotional glycosuria. Glycosylated Hb(HbA 1c) & its significance. Glycosylated Hb (HbA1c) is formed by post-synthetic interaction between Hb and glucose, whereby glucose is attached to the N- terminal amino group of beta-chain by a ketoamine linkage. The normal levels range 3—6 gm% but increase 2—3 fold in uncontrolled diabetes mellitus. HbAtc is utmost help for monitoring the glycemic control of diabetic patients.
- 73. All steroid hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it. All steroid hormones are lipid soluble Steroid hormones
- 74. The Endocrine Glands • Adrenal Cortex • Secretes over 30 different steroid hormones (corticosteroids) – Mineralocorticoids • Aldosterone: maintains electrolyte balance – Glucocorticoids • Cortisol: – Stimulates gluconeogenisis – Mobilization of free fatty acids – Glucose sparing – Anti-inflammatory agent – Gonadocorticoids • testosterone, estrogen, progesterone
- 75. Types of steroid hormones • Glucocorticoids; cortisol is the major representative in most mammals • Mineralocorticoids; aldosterone being most prominent • Androgens such as testosterone • Estrogens, including estradiol and estrone • Progestogens (also known a progestins) such as progesterone
- 76. The Endocrine System • The Adrenal Cortex secretes 3 classes of hormones, all steroid hormones: – gluticocorticoids mineralocorticoids – androgenic hormones • One at a time… – gluticocorticoids: – accounts for 95% of adrenal cortex hormone production – the level of glucose in the blood – Released in response to stress, injury, or serious infection - like the hormones from the adrenal medulla.
- 77. The Endocrine System • Mineralocorticoids: – work to regulate the concentration of potassium and sodium in the body. • Prolonged in adrenal cortex hormone results in Cushing’s Disease. • Signs & Symptoms of Cushing’s Disease: – in blood sugar levels – unusual body fat distribution – rapid mood swings
- 78. The Endocrine System • And - if there is an in mineralocorticoids as well – A serious electolyte imbalance will occur due to the potassium excretion by the kidney, which results in hypokalemia. • Sodium can also be retained by the kidney, resulting in hyponatremia. – Causes: • dysrhythmias • coma • death – usually results from a tumor - TX? Removal of tumor.
- 79. The Endocrine System • Gonads and Ovaries: – the endocrine glands associated with human reproduction. – Female ovaries produce eggs – Male gonads produce sperm • both have endocrine functions. • Ovaries: – located in the abdominal cavity adjacent to the uterus. – Under the control of LH and FSH from the anterior pituitary they manufacture • estrogen • protesterone
- 80. The Endocrine System • Estrogen and Progesterone have several functions, including sexual development and preparation of the uterus for implantation of the egg. • Testes: – located in the scrotum – produce sperm for reproduction – manufacture testosterone - • promotes male growth and masculinization – Controlled by anterior pituitary hormones FSH and LH.
- 81. Steroid hormones • Are not packaged, but synthesized and immediately released • Are all derived from the same parent compound: Cholesterol • Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER • Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
- 82. Steroid hormones • Steroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins. • Corticosteroid binding globulin carries cortisol • Sex steroid binding globulin carries testosterone and estradiol • In some cases a steroid is secreted by one cell and is converted to the active steroid by the target cell: an example is androgen which secreted by the gonad and converted into estrogen in the brain
- 83. Steroids can be transformed to active steroid in target cell
- 84. Steroidogenic Enzymes Common name "Old" name Current name Side-chain cleavage enzyme; desmolase P450SCC CYP11A1 3 beta-hydroxysteroid dehydrogenase 3 beta-HSD 3 beta-HSD 17 alpha-hydroxylase/17,20 lyase P450C17 CYP17 21-hydroxylase P450C21 CYP21A2 11 beta-hydroxylase P450C11 CYP11B1 Aldosterone synthase P450C11AS CYP11B2 Aromatase P450aro CYP19
- 86. Steroid hormone synthesis All steroid hormones are derived from cholesterol. A series of enzymatic steps in the mitochondria and ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones and intermediates. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. This step is carried out by the Steroidogenic Acute Regulatory Protein (StAR)
- 87. Steroid hormone synthesis •The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from uptake of cholesterol-containing low density lipoproteins. •Lipoproteins taken up from plasma are most important when steroidogenic cells are chronically stimulated.
- 89. 1,25-dihydroxy Vitamin D3 is also derived from cholesterol and is lipid soluble Not really a “vitamin” as it can be synthesized de novo Acts as a true hormone 1,25-Dihydroxy Vitamin D3
- 90. Fatty Acid Derivatives - Eicosanoids • Arachadonic acid is the most abundant precursor for these hormones. Stores of arachadonic acid are present in membrane lipids and released through the action of various lipases. The specific eicosanoids synthesized by a cell are dictated by the battery of processing enzymes expressed in that cell. • These hormones are rapidly inactivated by being metabolized, and are typically active for only a few seconds.
- 91. Fatty Acid Derivatives - Eicosanoids • Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids. • The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes.
- 92. The Endocrine Glands • Gonads – testes (testosterone) = sex characteristics • muscle development and maturity – ovaries (estrogen) = sex characteristics • maturity and coordination • Kidneys (erythropoietin) – regulates red blood cell production
- 93. Regulation of hormone secretion Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are: receipt of stimulus synthesis and secretion of hormone delivery of hormone to target cell evoking target cell response degradation of hormone
- 94. 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.
- 95. Control of Endocrine Activity The concentration of hormone as seen by target cells is determined by three factors: •Rate of production •Rate of delivery •Rate of degradation and elimination
- 96. Control of Endocrine Activity 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, as described below in more detail.
- 97. Control of Endocrine Activity 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.
- 98. Control of Endocrine Activity Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Shutting off secretion of a hormone that has a very short half-life causes circulating hormone concentration to plummet, but if a hormone's biological half-life is long, effective concentrations persist for some time after secretion ceases.
- 99. Feedback Control of Hormone Production Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion
- 100. Negative Feedback • Negative feedback is the primary mechanism through which your endocrine system maintains homeostasis • Secretion of a specific hormone s turned on or off by specific physiological changes (similar to a thermostat) • EXAMPLE: plasma glucose levels and insulin response
- 101. Inputs to endocrine cells
- 102. Neural control • Neural input to hypothalamus stimulates synthesis and secretion of releasing factors which stimulate pituitary hormone production and release
- 103. Chronotropic control • Endogenous neuronal rhythmicity • Diurnal rhythms, circadian rhythms (growth hormone and cortisol), Sleep- wake cycle; seasonal rhythm
- 104. Episodic secretion of hormones • Response-stimulus coupling enables the endocrine system to remain responsive to physiological demands • Secretory episodes occur with different periodicity • Pulses can be as frequent as every 5-10 minutes
- 105. • The most prominent episodes of release occur with a frequency of about one hour—referred to as circhoral • An episode of release longer than an hour, but less than 24 hours, the rhythm is referred to as ultradian • If the periodicity is approximately 24 hours, the rhythm is referred to as circadian – usually referred to as diurnal because the increase in secretory activity happens at a defined period of the day. Episodic secretion of hormones
- 107. Circadian Clock
- 108. Physiological importance of pulsatile hormone release • Demonstrated by GnRH infusion • If given once hourly, gonadotropin secretion and gonadal function are maintained normally • A slower frequency won’t maintain gonad function • Faster, or continuous infusion inhibits gonadotropin secretion and blocks gonadal steroid production
- 109. Clinical correlate • Long-acting GnRH analogs (such as leuproline) have been applied to the treatment of precocious puberty, to manipulate reproductive cycles (used in IVF), for the treatment of endometriosis, PCOS, uterine leiomyoma etc
- 110. Feedback control • Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion • Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation
- 111. Negative feedback effects of cortisol
- 112. Substrate-hormone control • Glucose and insulin: as glucose increases it stimulates the pancreas to secrete insulin
- 113. Feedback control of insulin by glucose concentrations
- 114. The Endocrine Response to Exercise
- 115. Regulation of Glucose Metabolism During Exercise • Glucagon secretion increases during exercise to promote liver glycogen breakdown (glycogenolysis) • Epinephrine and Norepinephrine further increase glycogenolysis • Cortisol levels also increase during exercise for protein catabolism for later gluconeogenesis. • Growth Hormone mobilizes free fatty acids • Thyroxine promotes glucose catabolism
- 116. Hormonal Effects on Fluid and Electrolyte Balance • Reduced plasma volume leads to release of aldosterone which increases Na+ and H2O reabsorption by the kidneys and renal tubes. • Antidiuretic Hormone (ADH) is released from the posterior pituitary when dehydration is sensed by osmoreceptors, and water is then reabsorbed by the kidneys.
- 117. The Endocrine System • Endocrine Emergencies: • Diabetes Mellitus – one of the most common diseases in North America. – insulin secretion by the Beta () cells of the islets of Langerhans in the pancreas. • Complications of Diabetes: – contributes to heart disease – stroke – kidney disease – blindness
- 118. The Endocrine System • Pathophysiology of Diabetes: • Glucose Metabolism – Glucose (dextrose) is a simple sugar required by the body to produce energy. – Sugars, or carbohydrates, are 1 of 3 major food sources used by the body. • The other 2 major food sources are – proteins – fats • Most sugars in the human diet are complex and must be broken down into simple sugars: glucose, galactose and fructose - before use.
- 119. The Endocrine System • Breakdown of sugars is carried out by enzymes in the gastro intestinal system. – As simple sugars, these are absorbed from the GE system into the body. – More than 95% enter the body as glucose. • To be converted into energy, glucose must first be transmitted through the cell membrane. BUT - the glucose molecule is large and doesn’t readily diffuse through the cell membrane.
- 120. The Endocrine System • Glucose must pass into the cell by binding to a special carrier protein on the cell’s surface. – Facilitated diffusion - doesn’t use energy. The carrier protein binds with the glucose and carries it into the cell. • The rate at which glucose can enter the cell is dependent upon insulin levels. – Insulin serves as the messenger - travels via blood to target tissues. – Combines with specific insulin receptors on the surface of the cell membrane.