2 Section 1 IntroductionI. Organization of Endocrine SystemThe functions of the body are regulated by the nervous and the endocrine system.The endocrine system consists of endocrine glands and cells that secrete hormones in various tissues.
3 Chapter 11, ENDOCRINE SYSTEM The material in this lecture covers generalization common to all hormone or to specific groups of hormones.The chemical nature of the hormones and their mechanisms of action are covered.
4 Endocrine glands:Glands that do not use ducts to convey the secretion to a neighboring target, they are also called ductless glands.The secretions, known hormones, circulate all over the body in the blood but may produce effects only in selected sites.The target organ(s) may or may not be near the site of production of the hormone.
5 A hormone – --chemical substance --is secreted into the internal body fluids by one specialized cell or a group of cells and--has a physiological control effect on other cells of the body.
6 II. Endocrine vs. Nervous System Major communication systems in the bodyIntegrate stimuli and responses to changes in external and internal environmentBoth are crucial to coordinated functions of highly differentiated cells, tissues and organsUnlike the nervous system, the endocrine system is anatomically discontinuous.
7 Nervous systemThe nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone.Nervous control is electrical in nature and fast.
8 Hormones travel via the bloodstream to target cells The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular 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.
9 III. Transportation of Hormones 1, Endocrine, or telecrine: glands or specialized cells release hormones into the circulating blood that influence the function of cells at another location in the body.
10 Transportation of Hormones 2.Neuroendocrine: neurons secrete substances (neurohormones) that reach the circulating blood and influence the function of cells at another location of the body.
11 Transportation of Hormones 3. Paracrine. in which cells secret substances that diffuse into the extracellular fluid and affect neighboring cells.
13 IV. Classification of Hormones Proteins and Polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.Pancreas: 胰腺Pituitary：垂体parathyroid gland：甲状旁腺
14 2. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone)adrenal cortex：肾上腺皮质Ovary: 卵巢Testis(testes)： 睾丸Placenta: 胎盘ovary
15 3. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine)
16 V. Properties of the hormone effect 1. SpecificityThe special feature of the the target cells is the presence of receptors which can “attract” and interact with the hormone.
17 The receptors may be present either on the plasma membrane, or in the cytoplasm, or in the nucleus. These receptor molecules are protein in nature and may contain carbohydrate or phospholipid moieties.
18 2. Signal TransmissionThe role of the hormones is to transit the regulatory signals from the control (endocrine) system to the target cells (organs or glands).It could enhance or inhibit some function of the target.
19 3. High Biological Efficiency Low plasma concentration (nmol – pmol/L) great regulatory function
20 Signal amplification during the transmembrane and intracellular transmission
21 4. Interaction Between the Hormones (1) Synergistic effects. When two or more hormones work together to produce particular result their effect are said to be synergistic.These effects may be additive or complementary.Additive: Same effect of the hormones on one target organ, for example, epinephrine and norepinephrine on the heart rateComplementary: Work on different stages of a physiological procedure, for example, FSH (initiation) and testosterone (maintenance) on spermatogenesis
23 (2) Permissive effect. A hormone is said to have a permissive effect on the action of a second hormone when it enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone.Estrogen – Expression of progesterone receptors on uterus – progesterone effect on the uterus.Glucocorticoids – effects of catecholamines on cardiovascular system
25 (3) Antagonist Effects.In some situations the actions of one hormone antagonize the effects of another.Lactation during pregnancy is prevented because the high concentration of estrogen in the blood inhibits the milk secretion and action of prolactin.
26 VI. Mechanisms of Hormonal Action The first step of a hormone’s action is to bind to specific receptors at the target cell.Locations for the different types of hormones:1) On the surface of the cell membrane.protein, peptide, and catecholamine hormones2) In the cell cytoplasm.steroid hormones3) In the cell nucleus.thyroid hormones (T3 and T4)
27 1.Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions Hydrophilic hormones (proteins, peptides and catecholamine)--bind the receptors on the membrane,--activate some enzyme on the membrane,-- regulate the concentration of some messengers (second messengers) in the cytoplasm. .
46 4. Hormones Secreted from the Posterior Pituitary vasopressin and oxytocinproduced in neuron cell bodies within the supraoptic and paraventricular nuclei of the hypothalamustransported to the posterior pituitary by nerve fibers of the hypothalamo-hypophyseal tract.
47 II. Physiological Function of Hormones Secreted From Anterior and Posterior Pituitary
48 1.Growth Hormone Physiological functions of growth hormone. 1) Growth effectGrowth hormone stimulates cell division, especially in muscle and epiphyseal cartilage of long bones.The result is muscular growth as well as linear growth.
49 GH also stimulates growth in several other tissues, e.g. skeletal muscle, heart, skin, connective tissue, liver, kidney, pancreas, intestines, adrenals and parathyroids.Hypersecretion of GH leads to cause gigantism in children and acromegaly in adult.Hyposection of GH results in dwarfism during childhood.
51 Effect of hypophysectomy on growth of the immature rhesus monkey. Both monkeys were the same size and weight 2 years previously, when the one on the left was hypophysectomized.
52 Effect of growth hormone treatment for 4 days on the proximal tibial epiphysis of the hypophysectiomized rat.Note that increased width of the unstained cartilage plate in the tibia of the right, compared with the control in the left.
53 Growth Hormone Excessin childhood leads to GIGANTISM
54 If an acidophilic tumor occur after adolescence – that is , after the epiphyses of the lone bones have fused with shafts– the person cannot grow taller,but the soft tissue can continue to grow and the bones can grow in thickness.This condition is known as acromegaly.
55 Growth Hormone Excessin adulthood leads to ACROMEGALY
56 Receptor mechanism of the growth hormone effect GH somatomedins (SM) （also called insulin-like growth factor, IGF) in the liver growth of bone and other peripheral tissues.
57 2) Metabolic effects of GH A, On Protein metabolismEnhance amino acid transport to the interior of the cells and increase RNA translation and nuclear transcription of DNA to form mRNA, and so increase rate of protein synthesis.GH also reduces the breakdown of cell proteins by decreasing catabolism of protein.
58 B, On fat metabolismCause release of fatty acids from adipose tissue and then increasing the concentration of fatty acids.Therefore, utilization of fat is used for providing energy in preference to both carbohydrates and proteins.
59 C. On glucose metabolism Decreases cellular uptake of glucose and glucose utilization,leads to increase of the blood glucose concentration.
60 (2) Regulation of GH secretion The plasma concentration of GH changes with age. 5 – 20 years old, 6ng/ml; 20 – 40 years old, 3ng/ml; 40 –70 years old, 1.6ng/ml.The change of GH concentration within one day.
61 - - - - 1) Role of hypothalamus and feedback mechanism + SSGRH--PituitaryGHLiverTarget tissuesSM+ increase the secretion; - inhibit the secretion
62 2) Other factors that affect the GH secretion A, Starvation, especially with severe protein deficiencyB, Hypoglycemia or low concentration of fatty acids in the bloodC, ExerciseD, ExcitementE, Trauma
63 2. Prolactin (PRL)Physiological function of PRLOn breast: stimulate the development and milk secretionIn women, breasts development at puberty is stimulated by estrogen, progesterone, growth hormone, cortisol, insulin, thyroid hormones and prolactin.During pregnancy, great growth of breast tissues occurs by stimulation of estrogen, progesterone and prolactin but estrogen and progesterone inhibit the secretion of milk.
64 Immediately after the baby is born, the sudden loss of estrogen and progesterone secreted by the placenta allows the lactogenic effect of PRL to assume its nature milk promoting role, initiating milk secretion.After birth of the baby, the level of PRL secretion returns to the normal level before pregnancy but each time the mother nurses her baby causes a 10 to 20 fold surge in PRL secretion that lasts for about 1 hour. Lactation is maintained for nursing period.
66 2) Effect on sexual organs In women, PRL combined with PRL receptors in granulosa cells stimulates production of LH receptors. Through LH receptors, LH promotes ovulation and then formation of corpus luteum. (permissive effect)In male, PRL promotes growth of prostate glands and seminal vesicle, enhancing the effect of LH on the interstitial cells producing testosterone.
67 - (2) Regulation of PRL secretion 1) Hypothalamic hormones and feedback mechanismHypothalamus: PIF PRF-++Anterior pituitary: Prolactin+ increase the secretion; - inhibit the secretion
68 2) Milk rejection reflex Sucking, tactile stimulationAfferent nerve (somatic nerve)Centers including spinal cord and hypothalamusPRF secretionOxytocin secretionMyoepithelial cells contraction of mammary glandsPRL secretionMilk production increaseMilk flows
71 3. Synthesis and Release of Vasopressin (VP) and Oxytocin (OXT) Cells in neurohypophysis do not synthesize hormones but act simply as supporting structure for nerve fibers.
72 Vasopressin (VP), also called ADH, and oxytocin (OXT) are initially synthesized in the cell bodies of the supraoptic and paraventricuar nuclei of hypothalamusand are transported down to the nerve endings in the neurohypophysis by hypothalamic hypophyseal tract.
73 When nerve impulses are transmitted downward along the fibers from nuclei, the hormone is immediately released from secretary granules in the nerve endings by exocytosis and is absorbed into adjacent capillaries.
74 Roles of ADHAntidiuretic effect (refer to chapter 8)Pressure effect. High concentration of ADH have a potent effect of constricting the arterioles everywhere in the body, raise the resistance blood flow and blood pressure
76 (2) Role of Oxytocin (OXT) Effect on mammary glands.Cause the contraction of the myoepithelial cells that surround the outer walls of the alveoli of the mammary glands, press the milk from the alveoli to the duct and make it flow out --- milk ejectionUnconditioned and conditioned reflex
78 2) Effect on uterusOXT powerful stimulate the smooth muscle contraction, especially that towards the end of gestation.It is believed that OXT is at least partially responsible for causing birth of the baby
80 Section 3 Thyroid Gland Functional Anatomy largest endocrine glands in the body,weighting about 20 – 25g.
81 Composed of large numbers of closed follicles filled with colloid and lined with a layer of cuboidal epithelioid cells.The thyroid hormones are synthesized and secreted by the epithelioid cells but stored in colloid.
83 II. Production of Thyroid Hormones Iodide (I-) actively transported into the follicle and secreted into the colloid.Oxidized to iodine (Io).H2O2Hydrogen Peroxide
84 Iodine attached to tyrosine within thyroglobulin chain. Attachment of 1 iodine produces monoiodotyrosine (MIT).Attachment of 2 iodines produces diiodotyrosine (DIT).
85 Within the colloid, enzymes modify the structure of MIT and DIT and couple them together. When two DIT molecules are coupled together, a molecule of tetraiodothyronine, T4, or thyroxine, is produced.The combination of one MIT with one DIT forms triiodythyronine, T3.
86 Thyroid Hormone Synthesis: 3’35’5DITDIT + DIT = THYROXINE (T4)3, 5, 3’, 5’-TETRAIODOTHYRONINEMIT + DIT = TRIIODOTHYRONINE (T3)3, 5, 3’-TRIIODOTHYRONINE
88 Upon stimulation by TSH, Note that within the colloid T4 and T3 are still attached to thyroglobulin.Upon stimulation by TSH,the cells of the follicle take up a small volume of colloid by pinocytosis,hydrolyze the T3 and T4 from the thyroglobulin, andsecrete the free hormones into the blood.TSH
91 III. Biological Actions of Thyroid Hormones T3 and T4 (Almost all is deiodinated by one iodide ion, forming T3) bind with nuclear receptor,activate and initiate genetic transcription mRNAprotein synthesis in cytoplasmic ribosomes ----general increase in functional activity throughout the body.
92 On Metabolism Calorigenic action of thyroid hormones Thyroid hormones increase O2 consumption of most tissues in the body, increasing heat production and BMR.The mechanism of calorigenic effect of thyroid hormones may be:A: Enhances Na+-K+ ATPase activityB: Causes the cell membrane of most cells to become leaky to Na+ ions, which farther activates sodium pump and increases heat production.
94 (2) Effect on metabolism of protein, carbohydrate and fat On Protein Metabolism.Normally, T4 and T3 stimulates synthesis of proteins and enzymes, increasing anabolism of protein and causing positive balance of nitrogen.In patient with hyperthyroidism, catabolism of protein increases, especially muscular protein, which leads weigh-loss and muscle weakness.
95 In patients with hypothyroidism, myxedema develops because of deposition of mucoprotein binding with positive ions and water molecules in the interstitial spaces while protein synthesis decreases.Hypothyroidism
96 2) On carbohydrate metabolism A: Increase absorption of glucose from the gastrointestinal tractE: Enhance glycogenolysis, and even enhanced diabetogenic effect of glucagon, cortisol and growth hormone.C: Enhancement of glucose utilization of peripheral tissues.
97 3) On fat metabolismThyroid hormones accelerate the oxidation of free fatty acids by cells and increase the effect of catecholamine on decomposition of fat.Thyroid hormones not only promote synthesis of cholesterol but also increase decomposition of cholesterol by liver cells.The net effect of T3 and T4 is to decrease plasma cholesterol concentration because the rate of synthesis is less than that of decomposition.
98 2. Effect of Thyroid Hormones on Growth and Development Thyroid hormone is essential for normal growth and development especially skeletal growth and development.Thyroid hormones stimulate formation of dendrites, axons, myelin and neuroglia.A child without a thyroid gland will suffer from critinism, which is characterized by growth and mental retardation.Without specific thyroid therapy within three months after birth, the child with cretinism will remain mentally deficient throughout life.
100 3. Effects of Thyroid Hormone on Nervous System Thyroid hormones increase excitability of central nervous system.In hyperthyroidism, the patient is likely to have extreme nervousness, many psychoneurotic tendencies including anxiety complexes, extreme worry and paranoia, and muscle tremor.Hyperthyroidism
101 In addition, thyroid hormones can also stimulate the sympathetic nervous system. HypothyroidismThe hypothyroid individual is to have fatigue, extreme somnolence, poor memory and slow mentation.
102 4. Other Effects of Thyroid Hormone Effect on cardiovascular systemThyroid hormones have a significant effect on cardiac output because of increase in heart rate and stroke volume, (may through enhance calcium release from sarcoplasmic reticulum).
103 (2) Effect on gastrointestinal tract Thyroid hormones increase the appetite and food intake by metabolic rate increased.Thyroid hormones increase both the rate of secretion of the digestive juices and the motility of the gastrointestinal tract.Lack of thyroid hormone can cause constipation.
104 IV Regulation of Thyroid Hormone Secretion 1. Hypothalamic Pituitary Thyroid AxisEffect of TSHIncrease secretion of T4 and T3 by proteolysis of thyroglobulinIncrease synthesis of thyroid hormonesthrough enhancement of ioidide trapping, ioidination of tyrosine and coupling to form hormones3) Stimulate thyroid gland to growth, increasing size and number of thyroid cells
105 (2) TRH secreted by hypothalamus causes the anterior pituitary to produce and release of TSH. Cold and various emotional reactions can increase TRH secretion through nervous system and thenindirectly affect the secretion of TSH and thyroid hormones.
106 2. Feedback Mechanisms of Thyroid Hormones T3 and T inhibitory protein in anterior pituitaryreduces production and secretion of TSH,decrease response of pituitary to TRH.Because of the negative mechanism, the concentration of free thyroid hormone in the blood can be maintained within a normal range.
108 In the absence of sufficient dietary iodide the thyroid cannot produce adequate amounts of T4 and T3.The resulting lack of negative feedback inhibition causes abnormally high level of the TSH secretion, which in turn stimulate the abnormal growth of the thyroid (a goiter).
109 3. Autoregulation of Thyroid Hormone Secretion Without control of TSH, the thyroid gland can adapt itself function to iodide uptake, which is the autoregulation of thyroid gland.In normal individuals, large doses of iodide act directly on the thyroid gland to produce a mild and transit inhibition of hormone synthesis.When iodine is insufficient, the thyroid gland increases formation of hormones.
110 In patients with hyperthyroidism, iodides cause colloid to accumulate and the vascularity of hyperplastic gland to decrease,making iodide treatment considerable in preparing patients for surgery.
111 4. Effect of Autonomic Nervous System on Thyroid Activity The thyroid gland is innervated by both sympathetic nerve and parasympathetic nerve.Electrical stimulation of sympathetic nerve increases formation of thyroid hormoneswhile stimulation of cholinergic fibers (vagus nerve) inhibits secretion of thyroid hormone.
117 Hormones of the Adrenal Cortex all adrenal cortex hormones are steroidnot stored, synthesized as neededOC = OHOOHCH2OHOHOtestosteronecortisol
118 Adrenal Cortical Hormones The mineralocorticoids are secreted by zona glomerulosa,regulates the concentration of the extracellular fluid.Aldosterone is the principal mineralocorticoid.
119 The glucocorticoids are secreted by both zona fasciculata and zona reticularis, exhibiting an important effect on increasing blood glucose concentration.Cortisol is the principal glucocorticoid.Small amounts of sex hormones are secreted by the zona reticularis.
120 1. Biological Effects of Adrenocortical Hormones
121 On metabolism On carbohydrate metabolism. A, Stimulation of gluconeogenesis (formation of carbohydrate from protein and other substances) by the liver through two pathways.----Cortisol activates DNA transcription in the liver cell nuclei with formation of messenger RNAs that in turn lead to the array of enzymes required for gluconeogenesis.----The other is cortisol causes mobilization of amino acids from extrahepatic tissues, mainly from muscle.One of the effects of increased gluconeogenesis is a marked increase in glycogen storage in the liver cells.
122 B, Reduction of glucose utilization by the cells. Cortisol decrease the rate of glucose utilization by the cells everywhere in the body because of inhibition of response of cells to insulin.C, Elevate blood glucose concentration
123 2) On protein metabolism A. Cortisol mobilizes amino acids from the nonhepatic tissues and diminishes the tissue stores of protein.B. Cortisol decreases protein synthesis in body cells except those of the liver and increases catabolism of protein in many extrahepatic tissues especially in muscle and lymphoid tissue.C. In the presence of great excesses of cortisol, the muscles become weak and the immunity functions of lymphoid tissue decrease.
124 3) On fat metabolismA. Cortisol promote mobilization of fatty acids from adipose tissue which increases the concentration of free acids in the plasmaB. Increases oxidation of fatty acids in the liver cells for energy.
125 Cushing’ s SyndromeMany people with excess cortisol secretion develop a peculiar type of obesity, with excess deposition of fat in the chest and head regions of the body, giving a buffalo-like torso and a rounded face, a “moon-face”.
127 4) Effects on water and electrolytes Cortisol has a slight effect on enhancement of sodium reabsorption and potassium excretion by distal tubules and colleting ducts in kidney.It increases the rate of renal blood flow and then glomerular filtration rates, facilitating water excretion.In patients with adrenal insufficiency, excretion of water is so slow that there is a danger of water intoxication and only glococorticoids can repair this deficit.
128 (2) On blood cellsCortisol increase the production of red cells and platelets by stimulating bone marrow.Cortisol decrease the number of lymphocytes and eosinocytes because it causes atrophy of the all lymphoid tissues and promotion of destruction of lymphocytes and eosinocytes.
129 (3) On cardiovascular system Glucocorticoids are necessary for maintenance of normal blood pressure. There are three mechanisms at least.Cause permissive action, enhancing the response of vascular muscle to catecholamines.Inhibit synthesis of prostaglandins that have vasodilator effect.Reduces the permeability of capillaries, which is useful to maintenance of blood volume.
130 (4) Effect on stress.Almost any type of stress, whether physical or neurogenic, will cause increase in ACTH secretion, and consequent cortisol secretion. This increase is essential for survival.
131 (5) Other effects.Glucocorticoids also have many other effects such as:increase in production of HCl and pepsin,promotion of synthesis of fetal surfactant.Glucocorticoids have pharmacological effects including anti-inflammatory, antiallergic and antishock effect.
132 2. Regulation of Secretion of Adrenocortical Hormone Hypothalamus – Anterior Pituitary – Adrenocortical Axis(1) Action of ACTH: Cortisol secretion is almost entirely controlled by ACTH (adrenocorticotropin hormone)
133 ACTH causes formation of adrenocortical hormones by increasing cAMP as a second messenger and activates steps for controlling adrenocortical secretion.Long-term stimulation of the adrenal cortex by ACTH not only increases secretory activity but also causes hypertrophy and proliferation of the adrenocorticol cells.
134 (2) CRH (corticotropin releasing hormone) A, Action of CRHThe action of CRH is to promote synthesis and release of ACTH in the cells of anterior pituitary gland.B, Regulation of CRH secretionCRH is secreted in irregular bursts throughout the day and plasma ACTH and cortisol tends to rise and fall in response to these bursts.
135 Fluctuations in plasma ACTH and glucotorticoids throughout the day in a normal girl (age 16). The circadian rhythm is driven by impulses from the supra-chiasmatic nuclei11-OHCS 11-oxysteroids (glucocorticoids)
136 Any type of stress can enhance secretion of CRH through afferent nerve pathways on hypothalamus. Consequently, ACTH secretion increases and cortisol concentration becomes very high in the blood.CRH secretion is inhibited by cortisol via a feedback mechanism
137 (3) Feedback mechanismCortisol has direct negative feedbacks on the hypothalamus to decrease formation of CRHHigh circulating levels of cortisol inhibit secretion and formation of ACTH, decreasing response of anterior pituitary gland to CRH.
138 High levels of ACTH also inhibit CRH secretion by a negative feedback mechanism. These feedbacks help regulate the plasma concentration of cortisol toward a normal control level.
139 Clinical treatment of cortisol (large does and long time) always cause the atrophy of the adrenal gland. Please describe the mechanism.
140 Section 5 Parathyroid Gland, Vitamin D and Parafollicular Cells Self-study