Endocrine System. Human Physiology Unit 3

Transcription

1 Endocrine System Human Physiology Unit 3

2 Endocrine System Various glands located throughout the body Some organs may also have endocrine functions Endocrine glands/organs synthesize and release hormones Hormones travel in plasma to target cells

3 Functions of the Endocrine System Differentiation of nervous and reproductive system during fetal development Regulation of growth and development Regulation of the reproductive system Maintains homeostasis Responds to changes from resting state

4 Mechanisms of Hormone Regulation Hormones have different rates and rhythms of secretion Hormones are regulated by feedback systems to maintain homeostasis Receptors for hormones are only on specific effector cells Excretion of hormones vary for steroid hormones and peptide hormones

5 Regulation of Hormone Secretion Release of hormones occurs in response to A change from resting conditions Maintaining a regulated level of hormones or substances Hormone release is regulated by Chemical factors (glucose, calcium) Endocrine factors (tropic hormones, HPA) Neural controls (sympathetic activation) HPA = Hypothalamic-Pituitary Axis

6 Hormone Feedback Systems Negative feedback maintains hormone concentrations within physiological ranges Negative feedback Feedback to one level Long-loop Negative Feedback Feedback to two levels Hypothalamus-Pituitary-Gland Axis Loss of feedback control often leads to pathology

7 Negative Feedback Short-Loop Negative Feedback Long-Loop Negative Feedback

8 Hormone Transport Peptide/Protein Hormones Circulate in free forms (unbound) Short half life Degraded by circulating enzymes Examples Insulin: t ½ = 3-5 minutes Hypolthalamic hormones Pituitary hormones Parathyroid Hormone (PTH) Lipid Soluble Hormones Circulate bound to carrier or transport proteins (albumins) Remain in blood from hours to days Examples Androgens Estrogen, progesterone Glucocorticoids Mineralcorticoids Vitamin D Thyroid hormone Arachidonic acid derivatives

9 Hormone Receptors A hormone released in to plasma circulates throughout the entire body Only cells with the receptors for those hormones can respond Cell receptors have 2 functions Recognize and bind to hormone with high affinity Initiate a signal to intracellular effectors

10 Hormone Receptors Sensitivity is related to the number of receptors Plasma membrane receptors are constantly being synthesized and degraded Regulation as a response Changes in [receptor] may occur within hours Physiological conditions affect receptor number and affinity ph Temperature Ion concentration Diet Other chemicals (drugs)

11 Plasma Membrane Receptors Signal Transduction 2 nd Messenger Associated Hormones camp cgmp Adrenocorticotropic Hormone (ACTH) Luteinizing Hormone (LH) Human Chorionic Gonadotropin (hcg) Follicle-stimulating Hormone (FSH) Thyroid Stimulating Hormone (TSH) Antidiuretic Hormone (ADH) Thyrotropin Releasing Hormone (TRH) Parathyroid Hormone (PTH) Glucagon Atrial Natriuretic Peptide (ANP) 2 nd Messenger Associated Hormones Calcium IP 3 and DAG Tyrosine Kinase JAK Angiotensin II Gonadotropin-Releasing Hormone (GnRH) Antidiuretic Hormone (ADH) Angiotensin II Antidiuretic Hormone (ADH) Insulin Growth Hormone (GH) Leptin Prolactin

12 Hormone Effects Binding of hormones t their receptors trigger 3 types of responses 1. Acts on pre-existing channel-forming proteins to change membrane permeability 2. Activating pre-existing proteins by a 2 nd messenger 3. Activating genes resulting in protein synthesis Direct Effects Changes in cell function result from hormone binding Insulin causes cellular glucose/amino acid uptake Permissive Effects Hormone induced changes that facilitate the maximal response of a cell Insulin has a permissive effect on mammary gland cells, facilitating their response to prolactin

13 Hormone Excretion Steroid Hormone Excretion Excreted directly by the kidneys Metabolized (conjugated) by the liver which inactivates them and makes them more water soluble Peptide Hormone Excretion Deactivated by enzymes and excreted in urine or feces

14 Hypothalamic-Pituitary Axis Anterior Pituitary Neurosecretory cells in the hypothalamus communicate with endocrine cells in the anterior pituitary Hypothalamo-pituitary portal vessels Endocrine cells of the anterior pituitary secrete their hormones into general circulation Posterior Pituitary Hypothalamic neurons extend into the posterior pituitary Hypothalamohypophysialnerve tract Neurons of the Supraoptic Nucleus and Paraventricular Nucleus Hormones are stored and released from the posterior pituitary into general circulation

15 Hypothalamic-Pituitary Axis Hypothalamo-pituitary portal vessels Capillaries in Infundibulum Venule Capillaries in Anterior Lobe Venule General Circulation Hypothalamohypophysial Nerve Tract

16 Hypothalamus Hypothalamus Neural input to the neurosecretory cells of the hypothalamus control their actions Neurons from other parts of the brain Sensory feedback to the hypothalamus Neurosecretory cells secrete releasing and inhibiting hormones Hypophysiotropic Hormones Tropic hormones cause other hormones to be produced Tropic Hormones released by the hypothalamus that cause hormones to be released by the anterior pituitary

17 Hypothalamus Hypothalamus Hormone Target Tissue Actions Thyrotropin-Releasing Hormone (TRH) Anterior Pituitary (+) Thyroid stimulating Hormone (TSH) Gonadotropin-Releasing Hormone (GnRH) Anterior Pituitary (+) Follicle Stimulating Hormone (FSH) (+) Luteinizing Hormone (LH) Growth Hormone Releasing Hormone (GHRH) Somatocrinin Anterior Pituitary (+) Growth Hormone (GH) Somatostatin Anterior Pituitary (-) Growth Hormone (GH) (-) Thyroid Stimulating Hormone (TSH) Corticotropin-Releasing Hormone (CRH) Anterior Pituitary (+) Adrenocorticotropic Hormone (ACTH) (+) β endorphin Substance P Anterior Pituitary (+) Growth Hormone (GH) (+) Follicle Stimulating Hormone (FSH) (+) Luteinizing Hormone (+) Prolactin (-) Adrenocorticotropic Hormone (ACTH) Prolactin-Releasing Factor (PRF) Anterior Pituitary (+) Prolactin Dopamine (DA) Anterior Pituitary (-) Prolactin

18 Anterior Pituitary Anterior Pituitary Also called adenohypophysis Chromophils are the secretory cells of the anterior pituitary 7 different sub-types Secretes tropic hormones Causes target glands to secrete hormones Regulation of the anterior pituitary Feedback of the releasing/inhibiting hormones Feedback from target gland hormones Direct effects of neurotransmitters

19 Anterior Pituitary Anterior Pituitary Hormone Target Organ Actions Adrenocorticotropic Hormone (ACTH) Adrenal Cortex (+) Cortisol, DHEA Melanocyte Stimulating Hormone (MSH) Anterior Pituitary (+) Secretion of melatonin Growth Hormone (GH) Liver (and Muscle, Bone) (+) Insulin-Like Growth Factor (IGF-1) Prolactin Mammary Glands (+) production of milk Thyroid-Stimulating Hormone (TSH) Thyroid Gland (+) Thyroid Hormone (T3, T4) (+) iodide uptake Luteinizing Hormone (LH) Follicle Stimulating Hormone (FSH) Gonads Women granulosa cells Men Leydig cells Gonads Women granulosa cells Men Sertoli cells β-lipotropin Adipocytes Lipolysis β-endorphins Adipocytes (Brain opioid receptors) (+) progesterone Ovulation (+) testosterone Testicular growth (+) estrogen Follicle development Spermatogenesis Analgesia, food and water intake, body temperature regulation

20 Posterior Pituitary Posterior Pituitary Also called neurohypophysis Secretes 2 peptide hormones Oxytocin Antidiuretic Hormone (ADH) Secreted from the hypothalamus Supraoptic nucleus Paraventricular nucleus

21 Posterior Pituitary Posterior Pituitary Hormone Target Gland Actions Oxytocin Uterine smooth muscle Mammary Glands Causes uterine contraction Causes the milk ejection reflex Antidiuretic Hormone (ADH) Kidney tubules Controls plasma osmolality

22 Pineal Gland Pineal Gland Contains photoreceptor cells that secrete Melatonin Synthesized from tryptophan tryptophan serotonin melatonin Melatonin release: Stimulated by exposure to dark Inhibited by exposure to light Melatonin regulates circadian rhythms and reproductive systems

23 Thyroid Gland Thyroid Gland Neurons of the ANS terminate on blood vessels of the thyroid ACh Catecholamines Thyroid gland secretes 2 hormones Thyroid hormone Calcitonin Actions of TSH on the Thyroid 1. Immediate release of stored thyroid hormone 2. Increased iodide uptake and oxidation 3. Increase in thyroid hormone synthesis 4. Increase in the synthesis and secretion of prostaglandins by the thyroid 5. Stimulates the growth and maintenance of the thyroid

24 Thyroid Gland Feedback Regulation of thyroid hormone by long-loop negative feedback Stimulus for secretion of TRH from the hypothalamus Sleep Extreme cold Exercise Stress Low plasma glucose Thyroid Gland Thyroxine (T 4 ) is monitored in plasma for feedback

25 Thyroid Hormone Synthesis Thyroid Hormone produced: 90% T 4 10% T 3 Thyroid Gland Follicular cells form thyroid follicles Thyroid Hormone is synthesized inside the follicles Triiodothyronine (T 3 ) Thyroxine (T 4 ) Iodide is attached to tyrosine rings bound to thyroglobulin inside the follicle MIT+DIT = T 3 DIT+DIT = T 4 MCT: Thyroid hormone transporter

26 Thyroid Hormone TH Receptors Thyroid Gland In the tissues, T 4 is converted to T 3 which binds to nuclear hormone receptors Thyroid beta receptor (THβ1, THβ2) Liver, brain Modulates cholesterol and triglyceride levels Thyroid alpha receptor (THα1) Heart Modulates heart rate, contraction

27 Thyroid Gland Thyroid Hormone Direct Actions Permissive Actions Regulates cell metabolism Protein metabolism Triglyceride metabolism Glucose metabolism Increased cellular metabolism increases Oxygen consumption Heat production Maintains Healthy metabolic processes Normal growth and maturation Activity of Na + /K + /ATPase pumps Stimulates bone resorption Fetal neurologic development Neurologic functioning in adults Growth hormone secretion Skeletal maturation And more

28 Thyroid Hormone Pathologies Thyroid Gland Within physiological ranges, the permissive effects are modest The permissive effects of TH become pronounced when there are high/low circulating levels Hyperthyroidism Hypothyroidism

29 Thyroid Gland Calcitonin Parafollicular Cells (C Cells) Secrete Calcitonin Causes serum calcium levels to decrease Inhibits osteoclasts Used to treat Osteoporosis Osteoarthritis Paget bone disease Hypercalcemia Metastatic bone cancer

30 Parathyroid Gland Parathyroid Gland Produce Parathyroid Hormone (PTH) Works with vitamin D to increase serum Calcium levels Concomitant decrease in serum phosphate levels Water soluble hormone GPCR + camp receptors Acts on bone Osteoclast activity, proliferation Acts on kidneys Acts on DCT to increase calcium reabsorption

31 Pancreas Pancreas Islets of Langerhans have 4 secretory cell types Pancreatic hormones regulate carbohydrate, fat and protein metabolism Alpha cells Glucagon Beta cells Insulin Delta cells Somatostatin F cells Polypeptide regulating digestion

32 Pancreas Insulin A peptide hormone Secretion is regulated by Chemical control: serum glucose, amino acids Neural control: ANS Hormonal control: GI hormones Insulin (feedback) Glucagon Gastrin Cholecystokinin Secretin Actions of Insulin Facilitates the rate of glucose and amino acid uptake Cellular glucose uptake by glucose transporters GLUT transporters Primary transporter: GLUT4 Cellular amino acid uptake by amino acid transporters

33 Insulin Receptors Pancreas Tyrosine Kinase receptor Receptors on liver, muscle, adipocytes Receptor activation leads to the insertion of glucose transporters in the cell membrane Cell takes in glucose Promotes all of the actions on glucose

34 Insulin Actions Pancreas Actions Liver Cells Muscle Cells Adipocytes Glucose uptake Increased Increased Increased Glycogenesis Increased Increased Glycogenolysis Decreased Decreased Glycolysis Increased Increased Increased Gluconeogenesis Increased Other fatty acid synthesis ketogenesis urea cycle activity amino acid uptake protein synthesis proteolysis fat esterification lipolysis fat storage

35 Pancreas Glucagon Produced by pancreatic α cells and cells lining the GI tract Stimulus for glucagon release Low serum glucose Sympathetic stimulation Some amino acids Protein rich meal Inhibition of glucagon release High serum glucose Actions of Glucagon Liver glycogenolysis gluconeogenesis Adipocytes lipolysis

36 Pancreas Somatostatin Essential in carbohydrate, fat and protein metabolism Homeostasis of ingested nutrients Regulates pancreatic alpha and beta cells NOT the same as hypothalamic somatostatin

37 Adrenal Glands Adrenal Glands Stimulated by ACTH Derived from Cholesterol Region of Adrenal Cortex % of Cortex Hormones Released Example Zona Glomerulosa 15% Mineral Corticoids Aldosterone * Zona Fasciculata 78% Glucocorticoids Cortisol Zona Reticularis 7% Mineral Corticoids Androgens Glucocorticoids Aldosterone* Adrenal androgens* Estrogens * * We will discuss these hormones when we discuss renal and reproductive physiology

38 Adrenal Glands Glucocorticoids Glucocorticoids Direct effect on carbohydrate metabolism Glucocorticoids have various effects: Metabolic actions Neurologic actions Anti-inflammatory actions Growth-suppressing actions Regulation of ACTH Serum cortisol levels Diurnal rhythms People. With regular sleep/wake patterns, ACTH peaks 3-5 hours after sleep begins and declines throughout the day Psychologic and physiologic stress Adrenal Glands

39 Adrenal Glands Cortisol Most potent glucocorticoid Main secretory product of the adrenal glands Necessary for the maintenance of life and for protection from stress Half life of 90 minutes Deactivated by the liver Adrenal Glands Actions of Cortisol Increase blood glucose levels Promote gluconeogenesis in the liver Decreasing uptake of glucose by muscle and lymphatic cells Ultimate effect on the body is protein breakdown Suppression of immune system (-) bone formation (-) ADH secretion (+) gastric acid secretion Depress nerve cell function

40 Adrenal Glands Cortisol Adrenal Glands

41 Adrenal Glands Cortisol Stress Response Adrenal Glands

42 Organs That Have Endocrine Function Some organs have endocrine function in addition to their role as part of an organ system Organ Hormone Hormone Actions Liver Gastrointestinal Organs (Entetric endocrine system) Kidneys Insulin-like Growth Factor (IGF1) Thrombopoietin (THPO) Hepcidin MANY Hormones Erythropoietin Calcitriol Postnatal growth Platelet production Iron homeostasis Regulation of motility RBC production Vitamin D activation Heart Atrial Natriuretic Peptide (ANP) Decreases blood pressure Adipocytes Leptin Energy balance