9 The Endocrine System Yong Jeong, MD, PhD Department of Bio and Brain Engineering The Endocrine System Second controlling system of the body Nervous system is the fast-control system Uses chemical messengers (hormones) that are released into the blood Hormones control several major processes Reproduction Growth and development Mobilization of body defenses Maintenance of much of homeostasis Regulation of metabolism 1
Binding of ligands to membrane-spanning receptors activates diverse response mechanisms. Hormone Overview Hormones are produced by specialized cells Cells secrete hormones into extracellular fluids Blood transfers hormones to target sites These hormones regulate the activity of other cells 2
The Chemistry of Hormones Hormones are classified chemically as Amino acid based, which includes Proteins Peptides Amines Steroids made from cholesterol Prostaglandins made from highly active lipids Mechanisms of Hormone Action Hormones affect only certain tissues or organs (target cells or target organs) Target cells must have specific protein receptors Hormone-binding alters cellular activity 3
Effects Caused by Hormones Changes in plasma membrane permeability or electrical state Synthesis of proteins, such as enzymes Activation or inactivation of enzymes Stimulation of mitosis Promotion of secretory activity The Chemistry of Hormones Two mechanisms in which hormones act Direct gene activation Second-messenger system 4
Direct Gene Activation (Steroid Hormone Action) Diffuse through the plasma membrane of target cells Enter the nucleus Bind to a specific protein within the nucleus Bind to specific sites on the cell s DNA Activate genes that result in synthesis of new proteins Steroid hormone Cytoplasm Nucleus 1 2 Receptor protein Hormonereceptor 3 complex 4 New protein DNA mrna 5 Plasma membrane of target cell 6 Figure 9.1a, step 6 5
Second-Messenger System (Nonsteroid Hormone Action) Hormone binds to a membrane receptor Hormone does not enter the cell Sets off a series of reactions that activates an enzyme Catalyzes a reaction that produces a secondmessenger molecule (such as camp) Oversees additional intracellular changes to promote a specific response Nonsteroid hormone (first messenger) Enzyme Cytoplasm ATP 1 2 3 camp Second messenger Receptor protein Plasma membrane of target cell 4 Effect on cellular function, such as glycogen breakdown (b) Nonsteroid hormone action Figure 9.1b 6
Control of Hormone Release Hormone levels in the blood are mostly maintained by negative feedback A stimulus or low hormone levels in the blood triggers the release of more hormone Hormone release stops once an appropriate level in the blood is reached Hormonal Stimuli of Endocrine Glands Most common stimuli Endocrine glands are activated by other hormones Examples: Anterior pituitary hormones travel to target glands, such as the thyroid gland, to prompt the release of a particular hormone, such as thyroid hormone 7
(a) Hormonal stimulus 1 The hypothalamus secretes hormones that Hypothalamus 2 stimulate the anterior pituitary gland to secrete hormones that Anterior pituitary gland Thyroid gland Adrenal cortex Gonad (Testis) 3 stimulate other endocrine glands to secrete hormones Figure 9.2a Humoral Stimuli of Endocrine Glands Changing blood levels of certain ions stimulate hormone release Humoral indicates various body fluids such as blood and bile Examples: Parathyroid hormone and calcitonin are produced in response to changing levels of blood calcium levels Insulin is produced in response to changing levels of blood glucose levels 8
(b) Humoral stimulus 1 Capillary blood contains low concentration of Ca 2+, which stimulates Capillary (low Ca 2+ in blood) Thyroid gland (posterior view) Parathyroid glands PTH Parathyroid glands 2 secretion of parathyroid hormone (PTH) by parathyroid glands Figure 9.2b Neural Stimuli of Endocrine Glands Nerve impulses stimulate hormone release Most are under the control of the sympathetic nervous system Examples: The release of norepinephrine and epinephrine by the adrenal medulla 9
(c) Neural stimulus 1 Preganglionic sympathetic fiber stimulates adrenal medulla cells CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary 2 to secrete catecholamines (epinephrine and norepinephrine) Figure 9.2c Major Endocrine Organs Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pineal gland Thymus gland Pancreas Gonads (Ovaries and Testes) Hypothalamus 10
Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9.3 Pituitary Gland Size of a pea Hangs by a stalk from the hypothalamus in the brain Protected by the sphenoid bone Has two functional lobes Anterior pituitary glandular tissue Posterior pituitary nervous tissue Often called the master endocrine gland 11
Hormones of the Anterior Pituitary Six anterior pituitary hormones Two affect non-endocrine targets Growth hormone Prolactin Four stimulate other endocrine glands (tropic hormones) Thyroid-stimulating hormone (thyrotropic hormone) Adrenocorticotropic hormone Two gonadotropic hormones Hormones of the Anterior Pituitary Characteristics of all anterior pituitary hormones Proteins (or peptides) Act through second-messenger systems Regulated by hormonal stimuli, mostly negative feedback 12
Releasing hormones secreted into portal circulation Hypothalamus Anterior pituitary Hypophyseal portal system Growth hormone (GH) Posterior pituitary Adrenocorticotropic hormone (ACTH) Bones and muscles Prolactin (PRL) Mammary glands Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Thyrotropic hormone (TH) Thyroid Adrenal cortex Testes or ovaries Figure 9.4 Hormones of the Anterior Pituitary Growth hormone General metabolic hormone Major effects are directed to growth of skeletal muscles and long bones Plays a role in determining final body size Causes amino acids to be built into proteins Causes fats to be broken down for a source of energy 13
Hormones of the Anterior Pituitary Growth hormone (GH) disorders Pituitary dwarfism results from hyposecretion of GH during childhood Gigantism results from hypersecretion of GH during childhood Acromegaly results from hypersecretion of GH during adulthood Pituitary dwarf (left), Giant (center), Normal height woman (right) Figure 9.5 14
Hormones of the Anterior Pituitary Prolactin (PRL) Stimulates and maintains milk production following childbirth Function in males is unknown Adrenocorticotropic hormone (ACTH) Regulates endocrine activity of the adrenal cortex Thyroid-stimulating hormone (TSH) Influences growth and activity of the thyroid gland Hormones of the Anterior Pituitary Gonadotropic hormones Regulate hormonal activity of the gonads Follicle-stimulating hormone (FSH) Stimulates follicle development in ovaries Stimulates sperm development in testes Luteinizing hormone (LH) Triggers ovulation of an egg in females Stimulates testosterone production in males 15
Pituitary Hypothalamus Relationship Hormonal release is regulated by releasing and inhibiting hormones produced by the hypothalamus Hypothalamus produces two hormones These hormones are transported to neurosecretory cells of the posterior pituitary Oxytocin Antidiuretic hormone The posterior pituitary is not strictly an endocrine gland, but does release hormones Hormones of the Posterior Pituitary Oxytocin Stimulates contractions of the uterus during labor, sexual relations, and breastfeeding Causes milk ejection in a nursing woman 16
Hormones of the Posterior Pituitary Antidiuretic hormone (ADH) Inhibits urine production by promoting water reabsorption by the kidneys In large amounts, causes vasoconstriction leading to increased blood pressure Also known as vasopressin Optic chiasma Hypothalamic neurosecretory cells Hypothalamus Axon terminals Arterial blood supply Posterior lobe Capillary bed Anterior lobe of the pituitary Venous drainage ADH Oxytocin Kidney tubules Mammary glands Uterine muscles Figure 9.6 17
Thyroid Gland Found at the base of the throat Consists of two lobes and a connecting isthmus Produces two hormones Thyroid hormone Calcitonin Thyroid cartilage Epiglottis Common carotid artery Isthmus of thyroid gland Trachea Brachiocephalic artery Left subclavian artery Left lobe of thyroid gland Aorta (a) Gross anatomy of the thyroid gland, anterior view Figure 9.7a 18
Thyroid Gland Thyroid hormone Major metabolic hormone Composed of two active iodine-containing hormones Thyroxine (T 4 ) secreted by thyroid follicles Triiodothyronine (T 3 ) conversion of T 4 at target tissues Colloid-filled follicles Follicle cells Parafollicular cell (b) Photomicrograph of thyroid gland follicles (125 ) Figure 9.7b 19
Thyroid Gland Thyroid hormone disorders Goiters Thyroid gland enlarges due to lack of iodine Salt is iodized to prevent goiters Cretinism Caused by hyposecretion of thyroxine Results in dwarfism during childhood Figure 9.8 20
Thyroid Gland Thyroid hormone disorders (continued) Myxedema Caused by hypothyroidism in adults Results in physical and mental slugishness Graves disease Caused by hyperthyroidism Results in increased metabolism, heat intolerance, rapid heartbeat, weight loss, and exophthalmos Figure 9.9 21
Thyroid Gland Calcitonin Decreases blood calcium levels by causing its deposition on bone Antagonistic to parathyroid hormone Produced by parafollicular cells Parafollicular cells are found between the follicles Colloid-filled follicles Follicle cells Parafollicular cell (b) Photomicrograph of thyroid gland follicles (125 ) Figure 9.7b 22
Parathyroid Glands Tiny masses on the posterior of the thyroid Secrete parathyroid hormone (PTH) Stimulate osteoclasts to remove calcium from bone Stimulate the kidneys and intestine to absorb more calcium Raise calcium levels in the blood Calcitonin Calcitonin stimulates calcium salt deposit in bone. Thyroid gland releases calcitonin. Stimulus Rising blood Ca 2+ levels Calcium homeostasis of blood: 9 11 mg/100 ml BALANCE BALANCE Stimulus Falling blood Ca 2+ levels Osteoclasts degrade bone matrix and release Ca 2+ into blood. PTH Thyroid gland Parathyroid glands Parathyroid glands release parathyroid hormone (PTH). Figure 9.10 23
Adrenal Glands Sit on top of the kidneys Two regions Adrenal cortex outer glandular region has three layers Mineralocorticoids secreted by outermost layer Glucocorticoids secreted by middle layer Sex hormones secreted by innermost layer Adrenal medulla inner neural tissue region Adrenal gland Kidney Capsule Mineralocorticoidsecreting area Adrenal gland Medulla Cortex Kidney Medulla Cortex Glucocorticoidsecreting area Sex hormone secreting area Adrenal medulla Adrenal cortex Figure 9.11 24
Hormones of the Adrenal Cortex Mineralocorticoids (mainly aldosterone) Produced in outer adrenal cortex Regulate mineral content in blood Regulate water and electrolyte balance Target organ is the kidney Production stimulated by renin and aldosterone Production inhibited by atrial natriuretic peptide (ANP) Decreased Na + or increased K + in blood Decreased blood volume and/or blood pressure Kidney ACTH Stress Hypothalamus Corticotropinreleasing hormone Anterior pituitary Increased blood pressure or blood volume Renin Indirect stimulating effect via angiotensin Angiotensin II Direct stimulating effect Heart Atrial natriuretic peptide (ANP) Inhibitory effect Mineralocorticoidproducing part of adrenal cortex Enhanced secretion of aldosterone targets kidney tubules Increased absorption Increased blood of Na + and water; volume and increased K + excretion blood pressure Figure 9.12 25
Hormones of the Adrenal Cortex Glucocorticoids (including cortisone and cortisol) Produced in the middle layer of the adrenal cortex Promote normal cell metabolism Help resist long-term stressors Released in response to increased blood levels of ACTH Short term Spinal cord Hypothalamus Nerve impulses Stress Releasing hormones Corticotropic cells of anterior pituitary More prolonged Preganglionic Adrenal sympathetic medulla fibers ACTH Adrenal cortex Mineralocorticoids Glucocorticoids Short-term stress response Catecholamines 1. Increased heart rate 2. Increased blood pressure (epinephrine and 3. Liver converts glycogen norepinephrine) to glucose and releases glucose to blood 4. Dilation of bronchioles 5. Changes in blood flow patterns, leading to increased alertness and decreased digestive and kidney activity 6. Increased metabolic rate Long-term stress response 1. Retention of sodium and water by kidneys 2. Increased blood volume and blood pressure 1. Proteins and fats converted to glucose or broken down for energy 2. Increased blood sugar 3. Suppression of immune system Figure 9.13 26
Hormones of the Adrenal Cortex Sex hormones Produced in the inner layer of the adrenal cortex Small amounts are made throughout life Mostly androgens (male sex hormones) are made but some estrogens (female sex hormones) are also formed Adrenal Glands Adrenal cortex disorders Addison s disease Results from hyposecretion of all adrenal cortex hormones Bronze skin tone, muscles are weak, burnout, susceptibility to infection Hyperaldosteronism May result from an ACTH-releasing tumor Excess water and sodium are retained leading to high blood pressure and edema 27
Adrenal Glands Adrenal cortex disorders Cushing s syndrome Results from a tumor in the middle cortical area of the adrenal cortex Moon face, buffalo hump on the upper back, high blood pressure, hyperglycemia, weakening of bones, depression Masculinization Results from hypersecretion of sex hormones Beard and male distribution of hair growth Hormones of the Adrenal Medulla Produces two similar hormones (catecholamines) Epinephrine (adrenaline) Norepinephrine (noradrenaline) These hormones prepare the body to deal with short-term stress ( fight or flight ) by Increasing heart rate, blood pressure, blood glucose levels Dilating small passageways of lungs 28
Adrenal gland Kidney Capsule Mineralocorticoidsecreting area Adrenal gland Medulla Cortex Kidney Medulla Cortex Glucocorticoidsecreting area Sex hormone secreting area Adrenal medulla Adrenal cortex Figure 9.11 Pancreatic Islets The pancreas is a mixed gland and has both endocrine and exocrine functions The pancreatic islets produce hormones Insulin allows glucose to cross plasma membranes into cells from beta cells Glucagon allows glucose to enter the blood from alpha cells These hormones are antagonists that maintain blood sugar homeostasis 29
Stomach Pancreas (a) Figure 9.14a Exocrine cells of pancreas (b) Pancreatic islets Figure 9.14b 30
Exocrine cells of pancreas Alpha (α) cells Capillaries (c) Cord of beta (β) cells secreting insulin into capillaries Figure 9.14c Uptake of glucose from blood is enhanced in most body cells Insulin-secreting cells of the pancreas activated; release insulin into the blood Elevated blood sugar level Pancreas Insulin Tissue cells Glucose Glycogen Liver takes up glucose and stores as glycogen Blood glucose falls to homeostatic set point; stimulus for insulin release diminishes Stimulus Blood glucose level (e.g., after eating four jelly doughnuts) Blood glucose rises to homeostatic set point; stimulus for glucagon release diminishes Stimulus Blood glucose level (e.g., after skipping a meal) Low blood sugar level Liver breaks Glucose Glycogen down glycogen stores and Liver releases glucose to the blood Glucagon Glucagon-releasing cells of pancreas activated; release glucagon into blood Figure 9.15 31
Pineal Gland Found on the third ventricle of the brain Secretes melatonin Helps establish the body s wake and sleep cycles Believed to coordinate the hormones of fertility in humans Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9.3 32
Thymus Gland Located posterior to the sternum Largest in infants and children Produces thymosin Matures some types of white blood cells Important in developing the immune system Gonads Ovaries Produce eggs Produce two groups of steroid hormone Estrogens Progesterone Testes Produce sperm Produce androgens, such as testosterone 33
Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Figure 9.3 Hormones of the Ovaries Estrogens Stimulate the development of secondary female characteristics Mature female reproductive organs With progesterone, estrogens also Promote breast development Regulate menstrual cycle 34
Hormones of the Ovaries Progesterone Acts with estrogen to bring about the menstrual cycle Helps in the implantation of an embryo in the uterus Helps prepare breasts for lactation Menstrual cycle 35
Hormones of the Testes Produce several androgens Testosterone is the most important androgen Responsible for adult male secondary sex characteristics Promotes growth and maturation of male reproductive system Required for sperm cell production Other Hormone-Producing Tissues and Organs Parts of the small intestine Parts of the stomach Kidneys Heart Many other areas have scattered endocrine cells 36
Endocrine Function of the Placenta Produces hormones that maintain the pregnancy Some hormones play a part in the delivery of the baby Produces human chorionic gonadotropin (hcg) in addition to estrogen, progesterone, and other hormones Developmental Aspects of the Endocrine System Most endocrine organs operate smoothly until old age Menopause is brought about by lack of efficiency of the ovaries Problems associated with reduced estrogen are common Growth hormone production declines with age Many endocrine glands decrease output with age 37