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Endocrine System Carl B. Goodman, Ph.D. College of Pharmacy & Pharmaceutical Sciences Florida A&M University 308E FSH-SRC 599-3128 [email protected] Endocrine System: Homeostasis Hormone - Regulatory molecules secreted into blood stream Endocrine Gland - Ductless glands contains secretory cells - Synthesis or produce hormones Effector - Target cells or tissues - Contains receptors to produce some physiological response Endocrine System vs Nervous System Function Secretory Cells Nervous System Neuron Endocrine System Glandular Epithelial Cells & Neurosecretory Cells Distance Short (Synapse) Long (Blood) Location of Receptors In Effector Cells Plasma Membrane Plasma Membrane & Within the Cell Characteristics of Regulatory Effects Appears Rapid, Short Lived Slow, Long Lasting Diagram Pre & Post Neurons Synaptic Target Cells Endocrine System vs Nervous System Function Overall Function Nervous System Regulate Effectors *HOMEOSTASIS Endocrine System Regulate Effectors *HOMEOSTASIS Control Feedback Loop Yes (Nervous Reflex) Yes (Endocrine Reflex) Chemical Messenger Neurotransmitter Hormone (Proteins or Steroids) Effector Tissues Muscle & Glandular Tissues All Cell Types *Muscles, Bones, Glandular Effector Cells Post Synaptic Neurons Target Cells Endocrine Action Endocrine System Endocrine Glands CNS: Pituitary Gland Periphery: Pancreas, Thyroid, Parathyroid, Adrenal, Testes and Ovaries Organs with Partial Endocrine Functions Hypothalamus, Pineal Gland, Stomach, Duodenum, Liver, Thymus, Heart, Skin, Kidney, Lung and Placenta Types of Hormones: Lipid Soluble Steroids - Cortisol - Aldosterone - Androgens - Estrogen/Progesterone - Testosterone - Calcitrol (Kidney) Gas - Nitric Oxide (NO) Thyroids - Triiodothyronine (T3) - Thyroxine (T4) Types of Hormones: Water Soluble Glycoproteins - Follicle Stimulating Hormone (FSH) - Luteinizing Hormone (LH) - Thyroid Stimulating Hormone (TSH) Peptides - Anti-diuretic Hormone (ADH) (8 AA) - Oxytocin (8 AA) - Melanocyte Stimulating Hormone (MSH) - Thyroid Releasing Hormone (TRH) Proteins - Growth Hormone (191), Calcitonin (32 AA), Prolactin, Insulin (21 & 30 AA), ACTH (39 AA), Parathyroid Hormone (84 AA) Fatty Acids (Arachidonic acid) - Leukotrienes - Prostaglandins - Thromboxanes - Prostacyclins Types of Hormones: Amino Acids Amines (Water Soluble) - Norepinephrine (Tyrosine) - Epinephrine (Tyrosine) - Melatonin (Tryptophan) - Serotonin (Tryptophan) - Histamine (Histadine) Iodinated Amino Acid - Thyroxine (T4) - Triiodothyronine (T3) Hormone Circulation Endocrine Action: hormone is distributed in blood and binds to distant target cell Paracrine Action: hormone acts locally by diffusing from its source to target cells in the neighborhood Autocrine Action: hormone acts on the same cell that produced it Hormone Transport in Blood Protein hormones circulate in free form in blood Steroid (lipid) & thyroid hormones must attach to transport proteins (Carrier Molecules) synthesized by liver – improve transport by making them water-soluble – slow loss of hormone by filtration within kidney – create reserve of hormone • only .1 to 10% of hormone is not bound to transport protein = free fraction Synthesis and Metabolism General Mechanisms of Hormone Action Hormone binds to cell surface or receptor inside target cell Cell may then: – synthesize new molecules (Protein Synthesis) – change permeability of membrane (Ion channels) – alter rates of reactions (Enzymes) Each target cell responds to hormone differently – Liver cells: insulin stimulates glycogen synthesis – Adipose: insulin stimulates triglyceride synthesis Circadian Rhythm for all Hormones (Basal Level) - Ex. Cortisol: increased daytime and decreased at night Hormone Interaction Synergistic Permissive- a second hormone, strengthens the effects of the first Ex. thyroid strengthens epinephrine’s effect upon lipolysis or Estrogen and Progesterone are need for maturation of follicle Antagonistic ex. Insulin and Glucagon Prehormone ex. T4 converted to T3 ex. Vitamin D3 converted to 1,25 dihydroxyvitamin D3 Role of Hormone Receptors Constantly being synthesized & broken down A range of 2,000-100,000 receptors / target cell Down-regulation (Hypersecretion of Hormone) – excess hormone, produces a decrease in number of receptors • receptors undergo Endocytosis and are degraded – decreases sensitivity of target cell to hormone Up-regulation (Hyposecretion of Hormone) – deficiency of hormone, produces an increase in the number of receptors – target tissue more sensitive to the hormone H + R = HR Complex Intracellular Chemical Signal Autocrine: secreted in a local area ex. Prostaglandins Paracrine: neighboring cell ex. Histamine, Prostaglandins Hormone: secreted in blood… ex. Insulin, T4, and T3 Neurohormone: produced by neurons ex. Oxytocin, ADH Neurotransmitter or Neurohumor: Pheromone: produced by neurons and secreted into synapse ex. Acetylcholine and Epinephrine pheromones secreted in environment, modifies behavior ex. Sex Hormone Signal Transduction Pathway Steroids Hormone Protein Hormone Second Messengers cAMP cGMP Phospholipase C Ca++ Opposing 2nd Messenger System with Same Hormone Beta Adrenergic Receptors - Relaxation/Dilation = cAMP Alpha Adrenergic Receptors - Constriction = Phospholipase C Feedback Control System Negative Feedback Positive Feedback Hypothalamic-Pituitary System Neurohypophysis Adenohypophysis Pituitary Gland = Hypophysis Hypothalamic-Pituitary System Pars Tuberalis Pars Nervosa Pars Distalis Pars Intermedia Posterior Pituitary Gland: Neurohormones Anti-diuretic Hormone (ADH) or Vasopressin Osmoreceptors near Supraoptic Nucleus (Dehydration) (Alcohol) H2O is reabsorbed from the tubules of the kidney and returned to the blood instead of the urine (H20 is conserved) Decrease in rate of perspiration during dehydration Raises Blood Pressure by constricting Arterioles Oxytocin Stimulate contraction of uterine muscle (smooth muscle) Initiate milk ejection from the Alveolar Cells into the ducts of the breast in lactating women Melanocyte-Stimulating Hormone (MSH) Pars Intermedia (Corticotroph cells) Melanocytes - Melanin (Darkening of Skin) Pre-proopiomelanocortin 2o Addision’s Disease (skin darkening) Estrogen/Progesterone (skin darkening) Anterior Pituitary Gland Growth Hormone (Somatotrophin) Prolactin Tropic Hormones Adenocorticotrophic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Luteinizing Hormone (LH) Follicle Stimulating Hormone (FSH) Growth Hormone Produced by somatotrophs (191AA) Within target cells increases synthesis of Somatomedins and Insulin-like Growth Factors that act locally or enter bloodstream – common target cells are liver, skeletal muscle, cartilage and bone – increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins – stimulate lipolysis in adipose so fatty acids used for ATP – retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain Abnormal Levels of Growth Hormone Hypersecretion of GH Hyposecretion of GH During the growth years before ossification of Epiphyseal plates, causes increase in rate of skeletal growth = Gigantism After the growth years = Acromegaly -Excess cartilage growth forming new bones. -Enlarged hands, feet, jaws, separation of teeth, -*Soft Tissue (forehead and nose) During the growth years, results in stunted body growth = Pituitary Dwarfism Prolactin Hypothalamus regulates lactotroph cells Primary function is to generate/initiate milk secretion (Lactation) 1. During Pregnancy, high prolactin promote development of breast for milk secretion 2. At Birth of an Infant, suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production Mammary glands are primed with E/P, Cortisol, GH, T4 and Insulin Nursing ceases & milk production slows Abnormal Levels of Prolactin Hypersecretion of Prolactin Hyposecretion of Prolactin Causes lactation in non-nursing women Disruption of the menstrual cycle (Men) can cause impotence Insignificant except in women, who want to nurse feed their babies ACTH Hypothalamus releasing hormones stimulate corticotrophs Corticotrophs secrete ACTH & MSH ACTH stimulates cells of the adrenal cortex that produce glucocorticoids & TSH Hypothalamus regulates thyrotroph cells Thyrotroph cells produce TSH TSH stimulates the synthesis & secretion of T3 and T4 Metabolic rate stimulated Gonadotrophins Luteinizing Hormone Releasing hormones from hypothalamus stimulate gonadotrophs Gonadotrophs produce LH In females, LH stimulates – secretion of estrogen – ovulation of 2nd oocyte from ovary – formation of corpus luteum – secretion of progesterone In males, stimulates interstitial cells to secrete testosterone Follicle Stimulating Hormone Releasing hormone from hypothalamus controls gonadotrophs Gonadotrophs release follicle stimulating hormone FSH functions – initiates the formation of follicles within the ovary – stimulates follicle cells to secrete estrogen – stimulates sperm production in testes