CLINICAL CHEMISTRY INTRODUCTION TO ENDOCRINOLOGY OUTLINE • Introduction to Endocrinology o Endocrine System o Hormones o Classification of Hormones According to Composition and Structure o Classification of Hormones According to Tissue Origin o Hormonal Interaction o Hormone Concentrations o Feedback Control Mechanisms INTRODUCTION TO ENDOCRINOLOGY • Endocrinology - study of processes involved in regulation and integration of cells and organ systems by hormones o Focuses on endocrine system and its effects on target cells/tissues • Endocrine system - function is specific to particular cell/group of cells • Hormones - can regulate metabolic activity through positive or negative feedback o Chemical substances that act as messenger molecules in the body o Can bind to specific receptors on target cells/tissues o Can influence biochemical changes in cells/tissues • Gland - organ/tissues capable of secreting hormones ENDOCRINE SYSTEM • Group of ductless glands (endocrine) that secrete hormones necessary for normal growth and development, reproduction, and homeostasis • Comes from Greek “endo” meaning within; “crine” meaning secrete; endocrine - to secrete within • Is a network of ductless glands of internal secretions • It is considered to be the regulatory system of the body • It is regulated by means of control of hormone synthesis rather than by degradation. • Refers to the collection of hormones • Hormones serve as chemical messengers and influence biochemical changes • Major endocrine glands in humans: o Hypothalamus o Pituitary gland o Pineal gland o Thyroid gland o Parathyroid gland o Adrenal gland o Islets of Langerhans (pancreas) o Ovaries o Testes • Dedicated endocrine gland: o Hypothalamus, Pituitary gland, Thyroid gland, Parathyroid gland, Ovaries, Testes, Endocrine pancreas, Adrenal HORMONES • Each hormone is produced by a specific endocrine gland • Chemical signals produced by specialized cells (endocrine cells) secreted into the blood stream and carried to a target site of action as free hormone or bound to transport protein. o Hormones are directly released to the bloodstream o Globulins - serve as transport protein • They play an important role in the growth and development of an organism o Hormones regulate the processes that lead to growth • They are regulated by the metabolic activity either positive or negative feedback mechanism o Positive feedback mechanism - an increase in the product also increases the activity of the system and the production rate ▪ Reinforcement, increasing product increases activity & production o Negative feedback mechanism - an increase in the product decreases the activity of the system and the production rate ▪ If target product is reached, system activity will subside and there will be no reinforcement ▪ More commonly employed in the body ▪ Allows balance/homeostasis o Major function: to maintain the constancy of chemical composition of ECF and ICF (electrolytes, nutrients, etc.) • Hormone secretion can be stimulated and inhibited by: o Other hormones: stimulating- or releasing- hormones ▪ Ex. Thyroid-stimulating hormone (TSH), o Plasma concentrations of ions or nutrient, as wells as binding globulins ▪ Ex. Ca levels dictate parathyroid hormone (PTH) is released or inhibited from parathyroid gland (hypocalcemia/ hypercalcemia) ▪ Globulin - protein bound to hormones; determines sercretion of hormone into the plasma o Neurons and mental activity ▪ Neurons - can secrete hormones ▪ Neuroendocrine cells in CNS can stimulates release of hormones o Environmental changes, e.g. light or temperature • Summary of typical hormone roles: o Stress response : ex: cortisol, epinephrine ▪ Stress - positive (overjoy, overexcitement), negative (overwhelm, anxiety) ▪ Regulates heart rate, blood pressure, inflammation o Maintenance of Homeostasis : ex: insulin, glucagon, cortisol ▪ Maintain more or less constant conditions (homeostatis) ▪ Maintains plasma glucose level (essential to ATP, energy/fuel for cells, brain activity) ▪ Insulin - hypoglycemic agent ▪ Glucagon , cortisol - hyperglycemic agent ▪ Hyperglycemia - insulin is secreted to lower plasma glucose level ▪ Hypoglycemia - glucagon and cortisol are secreted to spike plasma glucose level
o Regulation of episodic or cyclic events : ex: estrogen, insulin, oxytocin ▪ Regulates lactation among lactating mothers ▪ Regulates pregnancy ▪ Regulates eating, and effects of eating (glucose levels) o Growth/overall regulation : ex: growth factors (growth hormone), tropic hormones ▪ Regulates overall growth and development ▪ Tropic hormone - hormones with suffix -tropic; regulates production of other hormones o Hormones may have more than one function . ▪ Ex. Cortisol is constantly made to maintain homeostasis but it is secreted in larger amounts in response to stress TYPES OF HORMONE ACTIONS / PATTERNS OF HORMONE COMMUNICATION • Autocrine : hormone secreted by a cell and acts on that cell o Hormone released would also bind to the specific receptor of the cell that released it to promote self-regulation of function o Secreted by cells into the ECF and affect the function of the same cells that produced them by binding got cell surface receptors • Paracrine : hormones secreted by a cell and acts on nearby, neighboring, or adjacent cells o Hormones are released into the interstitial space and bind to nearby cells to affect function o Secreted by cells into the ECF and affect nearby/ neighboring/adjacent cells of different type o Hormones secreted into the extracellular space can also regulate nearby cells without ever passing through the systemic circulation o Paracrine signaling : cells release signals that affect nearby target cells • Endocrine : o Released by glands or specialized cells into the circulating blood and influence the function of cells at another location the body o Affects distant cells • Neuroendocrine : Hormone secreted by nerve cells (endocrine cells is a neuron) into blood and acts on distant target cells • Juxtacrine : o Secreted hormone by endocrine cell is released and remain in the plasma membrane of the cell o From the surface/plasma membrane of endocrine cell, hormone can immediately act on nearby cell by binding on the receptor of the adjacent cell (cell-to-cell contact) • Exocrine : o Hormones secreted by endocrine cell are released into the lumen of the gut into GIT o Hormones can affect the functions of the GIT • Neurocrine o Hormones secreted by neurons are released into the extracellular space and bind to the receptor of nearby cells to affect their function o Similar to neuroendocrine in terms of origin o Differ in target cells ▪ Neuroendocrine - distant target cell; released into the bloodstream ▪ Neurocrine - nearby target cells ACTIONS OF HORMONES • Regulatory function : o Hormones maintain constancy of chemical composition of the ECF & ICF o Concentration must be maintained in homeostasis • Morphogenesis : o Some hormones play a role in controlling the growth and development of an organism o Development of organs, bones, tissues as part of the growth cycle of an individual • Integrative action : o Each hormone has a specific function o Hormones, by several endocrine glands & hormones, may be important in maintain a specific function o Several hormones may function together/interact to function as one or execute a particular function CLASSIFICATION OF HORMONES ACCORDING TO COMPOSITION AND STRUCTURE PEPTIDES AND PROTEINS • All proteins are synthesized in rough endoplasmic reticulum (RER); Ribosomes attach to ER (site for protein synthesis) • All secretory peptides are synthesized in polyribosomes as larger precursors, known as a prohormone or a preprohormones (precursors for peptide) o Synthesized and stored within the cell in the form of secretory granules o When there is a need for peptide hormones, secretory granules are cleaved to release hormones • All secretory peptide hormones are stored (vesicle/granules); receptor site is the cell membrane (CM) o Peptide/protein hormones cannot cross the CM o They cannot cross the cell membrane and thus, produce their effects on the outer surface of the cells • Destined for secretion outside the cell • Hydrophilic; water-soluble & unbound from carrier proteins o Peptide/protein hormones are free-form • Most hormones in body exist as peptide/protein hormone • Synthesized and stored within the cell in the form of secretory granules and are cleaved as needed • Examples: o Glycoprotein – Follicle-stimulating Hormone (FSH), Human Chorionic Gonadotropin (hCG), Thyroid-stimulating Hormone (TSH), Erythropoietin o Polypeptides – Adrenocorticotropic Hormone (ACTH), Antidiuretic Hormone/Arginine Vasopressin (ADH/AVP), Growth Hormone (GH), Angiotensin, Calcitonin, Cholecystokinin, Gastrin, Glucagon, Insulin, Melanocyte-Stimulating Hormone (MSH), Oxytocin, Parathyroid Hormone (PTH), Prolactin, Somatostatin
STEROIDS • All are synthesized in smooth endoplasmic reticulum (SER) • No storage forms • Cholesterol - common precursor molecule for steroids • Hydrophobic; receptor site is the nucleus o All are bound to protein carriers/transporter • Act by modulating gene expression, inherited genes • Onset of action is slower and lasts longer o Hormones bind in the nucleus • Steroid hormones are produced/made by the adrenal cortex, ovaries, testes, and placenta • Steroid hormones from these glands fall into 5 categories: o Progestins o Mineralocorticoids o Glucocorticoids o Androgens o Estrogens • Lipid molecules that have cholesterol as a common precursor • Example: o Aldosterone - sodium regulation o Cortisol - stress response o Estradiol - gynecologic hormone; female-predominant o Estrone - gynecologic hormone; female-predominant o Progesterone - gynecologic hormone; female-dom. o Testosterone - androgenic hormone; male-dominant AMINES/AMINO-ACID DERIVED HORMONES • Function similar to steroid or peptides • Synthesized in the cytoplasm • Derived from various amino acids and they are intermediary between steroid and protein hormones • Most are derived from Tyrosine and some from Tryptophan • Example: o Epinephrine, Norepinephrine - stress hormones o T3, T4 - thyroid hormones o Serotonin CLASSIFICATION OF HORMONES ACCORDING TO TISSUE ORIGIN • Hypothalamus - TRH, GnRH, CRF • Anterior Pituitary - TSH, ACTH. FSH, LH, Prolactin, GH • Posterior Pituitary - Vasopressin, Oxytocin • Adrenal Medulla - Epinephrine, Norepinephrine • Adrenal Cortex - Cortisol, Aldosterone • Parathyroid - Parathyroid hormone • Thyroid - T3, T4, Calcitonin • Pancreas - Insulin, Glucagon • Ovaries - Estrogen, Progesterone • Testes - Testosterone, other Androgens HORMONAL INTERACTION • Synergistic o 2 or more hormones are additive/complementary in effect to certain target cell o Ex. FSH & LH • Antagonistic o 1 hormone offsets another hormone o Ex. Plasma glucose level maintenance ▪ The regulation of plasma glucose involves insulin (increase blood glucose) and glucagon (decrease blood glucose) hormones • Permissive o 1 hormone will enhance the responsiveness of a target to another hormone o Ex. Increased thyroid hormone levels make tissues responsive to catecholamine • Potentiation Reaction o The presence of one hormone increases the action of another hormone o Ex. ACTH & androgen ▪ Increased ACTH, increases androgen action • Stimulatory Reaction o The presence of one hormone stimulates the secretion of another hormone o Ex. Prolactin & oxytocin (important during pregnancy) • Inhibitory Reaction o The presence of one hormone inhibits the secretion of another hormone offsets another hormone o Ex. Prolactin and FSH/GnRH HORMONE CONCENTRATIONS • Threshold - hormone will not have any physiological effect until hormone threshold is reached • Concentration effect - differential physiology depending on concentration of hormones o Ex. Testosterone - surge of testosterone after puberty causing development of secondary sex characteristics (increased muscle mass, body hair growth) • Half-life - the time it takes for the concentration of a hormone to reduce 50% o Liver and kidney - important in determining half-life o Liver filters the concentration of hormones via blood. o Kidney can excrete a certain amount of hormones o Endocrine hormones have the longest half-life due to the varying distance for the endocrine hormones to reach target cells o Autocrine hormones have the shortest half-life due to immediate adherence to the cell membrane of the same cell that secreted them • Receptor saturation - hormone receptors are not a set number; can down regulate If bombarded with hormones FEEDBACK CONTROL MECHANISMS • Hormones maintained by homeostatic mechanism • Negative Feedback Control o Increase in hormone decreases gland activity & production rate o Example: Regulation of blood calcium levels ▪ PTH - important for maintaining normal blood Ca ▪ Hypocalcemia (↓ Ca) - parathyroid gland will secrete PTH to normalize Ca levels ▪ Normocalcemia (normal Ca) - parathyroid glands and PTH activity gradually decreases due to reaching normal calcium levels o Critical for maintaining homeostasis • Positive Feedback Control o Reinforcement o Increase in product increases production rate o Example: Labor & Childbirth ▪ During normal delivery labor, the head of the baby will press up the cervix which will stimulate the nerves to stimulate the pituitary gland to produce oxytocin causing uterus to contract to allow the head of baby to move out of the body
o Example: Lactation ▪ During lactation, sucking of the offspring from the mother stimulates the production prolactin which induces milk production ▪ Frequent sucking of the offspring will cause increased prolactin production causing increased milk production of the mother ▪ Intake of soupy diet can also increase milk prod.