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Transcript
The endocrine system Introduction Endocrine system consist of endocrine gland and endocrine cell. Hormones :chemical messenger secreted by one endocrine gland or cell Classification of the hormones (1)proteins and polypeptides: insulin, glucagon, parathyroid (2)steroids : cortisol, aldosterone, estrogen, progesterone (3) derivatives of the amino acid tyrosine (amine) : thyroxine, E, NE Characteristics of hormones (1) they are present in the circulation in low concentrations. Ranges between pmol and μmol. (2)every hormones has it’s specific receptor (3)Interaction synergism: actions of several hormones are complementary and their combined effect is greater than the sum of the separate one antagonism: one hormone reduce another one’s function permissiveness: one hormone must be present in adequate amounts for the full exertion of another hormone’s effect. Mechanisms of hormone actions Hormone receptors and their activation Types of hormone receptors: 1. In or on the surface of the cell membrane. 2. In the cell cytoplasm. 3. In the cell nucleus Intracellular signaling after hormone receptor activation 1. some hormones change membrane permeability. open channel 2. some hormones activate intracellular enzymes when they combine with their receptors. 3. some hormones activate genes by binding with intracellular receptors. The number of hormone receptors is regulated The number of receptors in a target cell usually does not remain constant from day to day, or even from minute to minute. down-regulation: decrease production of receptors Up-regulation: increase production of receptors Second messenger mechanisms for mediating intracellular hormonal functions (hydrophilic hormones) PIP2: phosphatidylinositol biphosphate IP3: inositol triphosphate DAG: diacylglycerol Hormones that act mainly on the genetic machinery of the cell (Lipophilic hormones) 1. The steroid hormone enters the cytoplasm of the cell, where it binds with a specific receptor protein. 2. The combined receptor protein-hormone then diffuses into the nucleus. 3. the combination binds at specific sites on the DNA strands in the chromosomes, which activates the transcription process of specific genes to form messenger RNA. 4. The messenger RNA diffuses into the cytoplasm, where it promotes the translation process at the ribosomes to form new proteins. The pituitary hormones and their control by the hypothalamus The pituitary gland and its relation to the hypo The pituitary gland has two distinct parts-the anterior and posterior lobes. The anterior pituitary also known as the adenohypophysis, the posterior pituitary also known as the neurohypophysis Hypothalamic releasing and inhibitory hormones control anterior pituitary secretion Major hypophysiotropic hormones Hormone effect on the anterior pituitary thyrotropin-releasing hormone(TRH) Corticotropin-releasing Hormone(CRH) Gonadotropin-releasing Hormone(GnRH) stimulates release of TSH (thyrotropin) and prolactin stimulates release of ACTH (adrenocorticotropic hormone) stimulates release of LH (luteinizing hormone) and FSH (follicle-stimulating hormone) stimulates release of growth hormone inhibits release of growth hormone stimulates release of prolactin inhibits release of prolactin Growth hormone-releasing Hormone(GHRH) Growth hormone-inhibiting Hormone(GHIH) Prolactin –releasing hormone(PRH) Prolactin –inhibiting hormone(PIH) The anterior pituitary secretes six established hormones 1. growth hormone (GH), the primary hormone responsible for regulating overall body growth, is also important in intermediary metabolism. 2. thyroid-stimulating stimulating hormone hormone and growth (TSH), of the thyroid gland. 3. adrenocorticotropic hormone (ACTH), stimulates cortisol secretion by the adrenal 4. follicle-stimulating hormone (FSH), has different function in male and females. In females it stimulates growth and development of ovarian follicles, within which the ova, or eggs develop. Furthermore, FSH promotes secretion of the hormone estrogen by the ovaries. In males FSH is required for sperm production. 5. luteinizing hormone (LH), in females LH is responsible for ovulation, luteinization, and regulation of ovarian secretion of the female sex hormones, estrogen and progesterone. In males the same hormone stimulates the interstitial cells of Leydig in the testes to secrete the male sex hormone, testosterone, giving rise to its alternate name of interstitial cell-stimulating hormone (ICSH). 6. Prolactin (PRL) development females. and Its enhance milk function breast production in in is males uncertain, although evidence indicates that it may induce the production of testicular LH receptors. Furthermore, recent studies suggest that prolactin may enhance the immune system and support the development of new blood vessels at the tissue level in both sexes- both actions totally unrelated to its known roles in reproductive growth hormone GH is a small protein molecule that contain 191 amino acids in a single chain. It causes growth of almost all tissues of the body that are capable of growing. 1.GH promotes protein deposition in tissues enhancement of amino acid transport through the cell membranes enhancement of RNA translation to cause protein synthesis by the ribosomes. Increased nuclear transcription of DNA to form RNA. Decreased catabolism of protein and amino acids. 2.GH enhances fat utilization for energy 3.GH decreases carbohydrate utilization 4.necessity of insulin and carbohydrate for the growth-promoting action of hormone. 5.GH stimulates cartilage and bone growth Regulation of GH secretion GH is secreted in a pulsatile pattern, increasing and decreasing. Stimulate secretion: starvation, hypoglycemia and low concentration of fatty acids in the blood, exercise, excitement, trauma . GH is also regulated by growth hormone-releasing hormone and growth hormone inhibitory hormone. Abnormalities of GH secretion Dwarfism: lack of GH, Most instance of dwarfism result from generalized deficiency of anterior pituitary secretion during childhood. Gigantism: result from excessive GH during childhood. Acromegaly: result from excessive growth hormone in adult. Other hormones besides GH are essential ways for normal growth:thyroid hormone, insulin, androgens, estrogens. The neurohypophysis gland and its relation to the hypothalamus Paraventricular nucleus’s and supraoptic nucleus’s fibers release antidiuretic hormone and oxytocin which reserve in the neurohypophysis. ADH is formed primarily in the supraoptic nuclei, whereas oxytoxin is formed primarily in the paraventricular nuclei. Antidiuratic hormone Acts in kidney to regulate water balance and control blood pressure Oxytocin Function: (1)oxytocin causes contraction of the pregnant uterus (2)oxytocin aids in milk ejection by the breasts Regulation of oxytocin release Oxytocin secretion is increased by reflexes that originate within the birth canal during childbirth. Milkejection reflex: Oxytocin secretion is increased by reflexes that are triggered when the infant suckles the nipple. These reflexes also be called neurohumoral reflex. Psychological and emotional factors, such as fear, may inhibit the release of oxytocin. Anxiety,pain and sympathoadrenal stimulation release oxytocin alcohol inhibits its secretion. The thyroid hormones The thyroid gland secrets two significant hormones: thyroxine(T4) triiodothyronine (T3). Raw material of thyroid synthesis : iodine and thyroglobin. Iodine combine with thyroglobin produce T4 and T3. The TH are stored in the follicles in an amount sufficient to supply the body with its normal requirements of TH for 2 to 3 months. T4 secretion > T3 secretion T4 converted to T3 in most tissues, especially liver and kidney T3 is more active hormone than T4. On entering the blood, over 99 per cent of the T4 and T3 combines immediately with thyroxine-binding globulin, thyroxinebinding prealbumin, albumin. Physiological functions of the thyroid hormones 1.TH increase cellular metabolic activity. The basal metabolic rate can increase 60 to 100 per cent above normal. when large quantities of the hormones are secreted. . TH increase the number and activity of mitochondria. Increase the rate of formation of ATP, increase activity of the cell. Thyroid hormones increase active transport of ions through cell membranes. The activity of sodium –potassium ATPase increases. 2. Effect of TH on growth Skeletal growth : promotion of skeletal maturation 3.Promote growth and development of the brain during fetal life and for the first few years of postnatal life. Lack of thyroid hormone after birth and without therapy with thyroid hormones, this disease is called “cretinism”. Failure of body growth and by mental retardation. 4. Effects of TH on specific bodily mechanisms (1)stimulation of carbohydrate metabolism (2)stimulation of fat metabolism (3)increased requirement for vitamins. (4)increased basal metabolic rate (5)decreased body weight 5. Effects of TH on the cardiovascular system (1)increased blood flow and cardiac output. (2)increased heart rate (3)increased heart strength 6. Increased gastrointestinal motility, increased respiration 7. excitatory effects on the CNS slightly increase in TH, makes the muscles react with vigor, excessive hormone, because of excess protein catabolism, muscles become sluggish. 8. effect on sleep, other endocrine glands Difficult to sleep, insulin increase. Regulation of TH secretion TH is regulated by the hypothalamus-pituitary-thyroid axis. If lack of iodine in food, T3 and T4 synthesis decrease, the inhibition of TSH is free, TSH is higher than normal condition, the thyroid gland is enlargement. (endemic goiter) Stress,cold hypothalamus — thyrotropin-releasing Hormone(TRH) + pituitary thyroid-stimulating Hormone(TSH) + thyroid gland Thyroid hormone T3 T4 — thyroid-stimulating hormone (TSH) stimulating hormone and growth of the thyroid gland. Diseases of Thyroid Gland Hyperthyroidism = overactive thyroid Increased metabolic rate Enlargement of thyroid gland (goiter) Weight loss, nervousness, irritability Intolerance to heat Bulging eyeballs Hypothyroidism = underactive thyroid Slowed metabolic rate, fatigue, weight gain Cretinism, if present and untreated at birth The adrenocortical hormones The adrenal gland: Paired glands; located on top of kidneys Each adrenal gland has two parts Medulla Inner portion Synthesizes/secretes E and NE (stress hormones) Cortex Outer portion Cortex zona reticularis: sex hormone, and rogens (dehydroepiandrosterone DHEA), estrogen zona glomerulosa: mineralocorticoids (aldosterone) zona fasciculata: glucocorticoids (cortisol, corticosterone) Functions of the mineralocorticoids -aldosterone Aldosterone Regulates Na+ and K+ balance ; promotes Na+ reuptake in kidney Deficiency of aldosterone : wasting of sodium chloride and hyperkalemia Excess aldosterone : causes hypokalemia and muscle weakness Functions of the glucocorticoids-hydrocortisol 1. It stimulates hepatic gluconeogenesis into carbohydrate within the liver. 2. It inhibits glucose uptake and use by many tissues, but not brain. It can increase blood glucose concentration. 3. It stimulates protein degradation in many tissues, especially muscle. 4.It facilitates lipolysis, the breakdown of lipid stores in adipose tissue, thus releasing free fatty acids into the blood. 5.Permissive actions cotisol strengthen the vasoconstriction of NE. 6.Role in adaptation to stress Resistance to Stress. When an animal or human is exposed to a wide variety of noxious stimuli, there is an increased secretion of ACTH and consequently rise in the circulatory glucocorticoid level. This rise is essential for survival. Noxious stimuli that increase the ACTH secretion is called “stressor”. The reason that an elevated circulatory glucocorticoid level is essential for resisting stress remains for the most part unknown. Regulation of cortisol secretion by adrenocorticotropic hormone from the pituitary gland Diseases of Adrenal Glands Cushing’s Disease –hyperactive adrenal cortex –rounded face & obesity –Thin, frail skin; poor wound healing Addison’s Disease = adrenal cortex insufficiency –Decreased appetite, weight loss –Cold intolerance –Stress susceptibility pancreas (1)the acini, which secrete digestive juices into the duodenum (2)the islets of Langerhans, which secret insulin and glucagon into the blood. Insulin and its metabolic effects Insulin is secreted by beta cells in islets of Langhans. Functions: Insulin lowers blood glucose, amino acid, and fatty acid levels. promote the synthesis of protein, fat and glucogen. It causes fat storage in the adipose tissue. All the excess carbohydrates that can not be stored as glycogen are converted into fats stored in the adipose tissue. In the case of proteins, insulin has a direct in promoting amino acid uptake by cells and conversion of these amino acids into protein. Regulation of insulin 1.The primary stimulus for increased insulin secretion is an increase in blood glucose concentration . An elevated blood glucose level directly stimulates synthesis and release of insulin by the beta cells 2. An elevated blood amino acid level directly stimulates beta cells to increase insulin secretion. 3.the major gastrointestinal hormones secreted, the insulin increase. 4.the parasympathetic nerve stimulate insulin release, on the contrary, the sympathetic nerve inhibit insulin release. Diabetes:lack of insulin glucagon and its function A hormone secreted by alpha cells of the islets of Langerhans Functions: Breakdown of liver glycogen and increased gluconeogenesis in the liver, therefore increase glucose concentration. Regulation of glucagon increased blood glucose inhibits glucagon secretion. Increased blood amino acids stimulate glucagon secretion. Endocrine control of calcium and metabolism Extracellular fluid calcium concentration normally is 2.4 mmol/L. Calcium metabolism is regulated by parathyroid hormone (PTH), vitamin D calcitonin. Parathyroid (PTH) hormone Secreted by parathyroid gland respond to reduced blood calcium levels. Function: 1. PTH stimulate osteoclast to remove Ca2+ from the bone matrix and inhibit osteoblast from making new bone. 2. Kidney: PTH increased Ca2+ reabsorption, PO42excretion. Regulation of PTH Fall in plasma Ca2+ concentration, the PTH increase . Calcitonin Produced by the C cells of the thyroid gland. Function It suppression of osteoclast bone absorption reducing plasma Ca2+ and PO42-. Regulation Concentration of Ca2+ increased ,The calcitonin increased. Vitamin D Vitamin D is obtained from the diet or synthesized by the skin as a result of irradiation of 7-dehydrocholesterol by ultraviolet rays from the sun. Circulating Vitamin D is first hydroxylated in liver to yields 25-hydroxycholecalciferol, further hydroxylation in the kidney yields the active form, 1,25- dihydroxycholecalciferol. Function of Vitamin D Promotes intestinal calcium and phosphate absorption. Deceases renal calcium and phosphate excretion. All in all, it can coordinate with PTH increase Ca 2+ .