Ch. 10: Endocrine System ● FUNCTIONS OF THE ENDOCRINE SYSTEM ○ Metabolism ○ Control of food intake and digestion ■ Regulates level of satiety and breakdown of food into nutrients ○ Tissue development ○ Ion regulation ○ Water balance ○ Heart rate & blood pressure regulation ○ Control of blood glucose and other nutrients ○ Control of reproductive functions ○ Uterine contractions and milk release ○ Immune system regulation ● PRINCIPLES OF CHEMICAL COMMUNICATION ○ Chemical Messengers: allow cells to communicate with each other to regulate bodily activities ■ Produced by glands ● Glands consist of epithelial cells that specialize in secretion ● CHARACTERISTICS OF THE ENDOCRINE SYSTEM ○ Composed of endocrine glands, hormones, and target tissues (hormone receptors) ■ Secrete hormones (substance secreted by endocrine tissues into the blood that acts on a target tissue to produce a specific response) into the bloodstream, not a duct! ■ Target Tissue: also known as effectors, site on which hormones act ○ Exocrine glands are not endocrine glands ■ Exocrine glands have ducts ● Carry secretions to the outside of the body (or into a hollow organ) ○ i.e. saliva, sweat, breast milk, digestive enzymes ● HORMONES ○ Chemical secreted by specialized cells that travels through the blood to distant target cells; regulate physiological processes ○ Chemical Nature of Hormones ■ Lipid-soluble vs. water-soluble hormones ● Lipid bilayer is selectively permeable that excludes watersoluble molecules, but allows lipid-soluble molecules to pass through ■ Lipid-Soluble Hormones ● Non-polar steroid, thyroid, and/or fatty-acid derivatives hormones ● Travel in bloodstream attached to transporter proteins ○ Rate at which lipid-soluble hormones are eliminated from bloodstream is reduced due to low solubility in blood water and small size ○ Without transporter proteins, lipid-soluble hormones would diffuse out of capillaries and be degraded by enzymes ■ Hydrolytic enzymes can metabolize free lipid- soluble hormones, excreting them in urine/bile ■ Water-Soluble Hormones ● Polar protein, peptide, and/or amino-acid derivatives hormones → cannot diffuse through lipid bilayer ● Short half-lives ○ Rapidly changing concentrations and regulate activities that have rapid onset and short duration ● Circulate as free hormones ○ Dissolve in blood and degraded by proteases ○ Most are large molecules → diffuse into tissue spaces more slowly ■ Capillaries of organs are very porous (fenestrated) ○ All hormones are destroyed either in circulation or target cells ○ Kidneys remove hormone breakdown products from the blood after watersoluble hormones are broken down by proteases ○ Target cells destroy water-soluble hormones when internalized via endocytosis ■ Lysosomal enzymes degrade them ■ Target cell recycles amino acids of peptide and protein hormones to synthesize new proteins ● CONTROL OF HORMONE SECRETION ○ 3 types of stimuli: Humoral, Neural, and Hormonal ○ Blood level of most hormones fluctuates within homeostatic range due to negative-feedback mechanisms (positive-feedback systems also regulate blood hormone levels in a few instances) ○ Stimulation of Hormone Release ■ Control by Humoral Stimuli ● Humoral Stimuli → blood-borne body fluids, circulate in the blood ●Sensitive to blood levels of particular substances like glucose, calcium, and sodium ● Examples: ○ Parathyroid (PTH hormone → secreted when low calcium ○ Antidiuretic (ADH) hormone → water-conservation ○ Insulin → secreted when high level of glucose ○ Aldosterone → secreted when high level of potassium ■ Control by Neural Stimuli ● Following action potentials, neurons release neurotransmitter into synapse with the cells that produce the hormone → neurotransmitter stimulates cells to increase hormone secretion ● Some neurons secrete chemical messengers directly into the blood when they are stimulated → Neuropeptides ○ Releasing Hormones: regulates secretion of hormones from cells of anterior pituitary gland; released from neurons in hypothalamus ■ Control by Hormonal Stimuli ● Occurs when a hormone secreted stimulates the secretion of other hormones ○ e.g. Tropic Hormones ■ Part of a process in which a releasing hormone from the hypothalamus stimulates release of tropic hormone from pituitary gland ■ Tropic hormone then travels to third endocrine gland and stimulates release of third hormone ○ Inhibition of Hormone Release ■ Involves the same 3 types of stimuli ● Inhibition of Release by Humoral Stimuli ○ Often when a hormone’s release is sensitive to presence of humoral stimulus, there exists a companion hormone whose release is inhibited by same humoral stimulus ■ Companion hormone counteracts effects of secreted hormone’s actions ● i.e. Atrial Natriuretic Peptide (ANP) (lowers BP) & Aldosterone (raises BP) ● Inhibition of Release by Neural Stimuli ○ If a neurotransmitter is inhibitory, the target endocrine gland does not secrete its hormone ● Inhibition of Release by Hormonal Stimuli ○ Some hormones prevent secretion of other hormones ○ Inhibiting Hormones → hormones from hypothalamus that prevent secretion of tropic hormones from pituitary gland ● REGULATION OF HORMONE LEVELS IN BLOOD 1. Negative Feedback a. Most hormones are regulated by negative-feedback mechanism i. Hormone’s secretion is inhibited by the hormone itself once blood levels have reached proper point and there is adequate hormone to activate target cell 1. i.e. Estrogen, GnRH, LH b. Self-liming system 2. Positive Feedback a. Some hormones, when stimulated by tropic hormone, promote synthesis and secretion of tropic hormone in addition to stimulating target cell i. Stimulates further secretion of original hormone 1. i.e. Progesterone ● HORMONE RECEPTORS & MECHANISMS OF ACTION ○ Receptors: protein molecule on cell surface or within cytoplasm that binds to a specific factor like a hormone, neurotransmitter, drug, or antigen ■ A hormone can only stimulate the cells that have the receptor for that hormone ■ Binds to a receptor site ● Shape and chemical characteristics of receptor sites only allow a specific hormone to bind to it → specificity ○ Classes of Receptors 1. Lipid-Soluble hormones bind to Nuclear Receptors a. Since lipid-soluble hormones are small, they diffuse through plasma membrane and bind to nuclear receptors (found in cell nucleus) i. Nuclear receptors can also be in cytoplasm, but move to nucleus when activated b. When hormones bind to nuclear receptors, hormone-receptor complex interacts w/ DNA in nucleus or other cell enzymes to regulate transcription of genes in target tissue (takes minutes to hours) c. Lipid-Soluble hormones may also rarely have rapid effects (less than a minute) on target cells due to membrane-bound receptors instead of nuclear receptors d. Examples of hormones that bind to nuclear receptors: i. Testosterone, Estrogen, Progesterone ii. Aldosterone, Cortisol 2. Water-Soluble hormones bind to Membrane-Bound Receptors a. Since water-soluble hormones are polar, they cannot pass through the plasma membrane i. Instead, they interact w/ membrane-bound receptors (found along plasma membrane) b. When hormone binds to receptor on outside of plasma membrane, hormone-receptor complex initiates a response inside the cell c. Examples of hormones that bind to membrane-bound receptors: i. Proteins, peptides, amino-acid derivatives (epinephrine, norepinephrine) ii. Glucagon, Prolactin ○ Action of Nuclear Receptors ● After lipid-soluble hormones diffuse across plasma membrane and bind to receptors, hormone receptor complex binds to DNA to produce response ■ Receptors that bind to DNA have fingerlike projections that recognize/bind to specific nucleotide sequences in DNA called hormone-response elements ● Combination of the hormone and its receptor forms a transcription factor ■ When the hormone-receptor complex binds to the hormone-response element, it regulates transcription of mRNA molecules ● Newly formed mRNA move to cytoplasm to be translated into specific proteins at the ribosomes ● Newly formed proteins produce the cell’s response to the hormone ● Target cells that synthesize new proteins in response to hormonal stimuli normally have a latent period of several hours between time the hormones bind to receptors and the time responses are observed ● Hormone-receptor complexes are eventually degraded within the cell, limiting length of time hormones influence the cell's activities ○ Membrane-Bound Receptors & Signal Amplification ● Membrane-bound receptors have peptide chains that are anchored in phospholipid bilayer of plasma membrane ● Membrane-bound receptors can activate responses in 2 ways: ■ Alter activity of G proteins at inner surface of plasma membrane ■ Other receptors directly alter activity of intracellular enzymes ● These pathways elicit specific responses in cells as well as the production of second messengers (chemical produced inside a cell once a hormone or another chemical binds to certain membrane bound receptors; activates set of events collectively known as second-messenger system) ■ i.e. Cyclic AMP (cAMP) 1. Membrane-Bound Receptors That Activate G Proteins 2. G Proteins That Interact With Adenylate Cyclase ○ Signal Amplification ● Hormones that stimulate synthesis of second messengers (water-soluble hormones) can produce an Instantaneous response since the response proteins are already present! ● Each receptor produces a large number of second messengers, leading to a cascade effect and amplification of the hormonal signal! ● Endocrine Glands and Their Hormones ○ Pituitary and Hypothalamus ■ Pituitary → rests in depression of sphenoid bone inferior to hypothalamus; “master gland” ● Anterior Pituitary (Adenohypophysis) ○ Epithelial cells from embryonic oral cavity; indirectly connected to hypothalamus via blood vessels ● Posterior Pituitary (Neurohypophysis) ○ Extension of the brain, composed of nerve cells ■ Hypothalamus → autonomic nervous system and endocrine control center of brain, below thalamus ● Connected to pituitary gland via infundibulum ● Controls pituitary gland via hormonal control & direct innervation ● Controls joy, anger, chronic stress and more! ● Hormonal Control of the Anterior Pituitary ○ Neurons of hypothalamus produce/secrete neuropeptides that act on anterior pituitary gland ■ Act as either releasing hormones or inhibiting hormones by traveling through hypothalamus-pituitary portal system ● Direct Innervation of the Posterior Pituitary ○ Stimulation of neurons within hypothalamus controls secretion of hormones from posterior pituitary ■ Cell bodies of these neurons are in hypothalamus, axons extend through infundibulum to the posterior pituitary ○ Hormones are produced in nerve cell bodies and transported through the axons to the posterior pituitary where they are stored in the axon endings ● Thyroid Gland ○ Highly vascular ○ Secrete thyroid hormones which bind to nuclear receptors and regulate rate of metabolism ■ Synthesized and stored within gland in thyroid follicles where the hormones attach to thyroglobulin (protein) ■ Between follicles is network of loose connective tissue that contains “C Cells” which secrete Calcitonin ○ Thyroid hormones have a negative-feedback effect on hypothalamus and pituitary ■ Increasing levels of thyroid hormones inhibit secretion of TSH-releasing hormone from hypothalamus and inhibit TSH secretion from anterior pituitary gland ● A loss of negative-feedback would result in excess TSH, causing them to enlarge (goiter) ○ Hypothyroidism: lack of thyroid hormone secretion ■ Cretinism: appears in children; results in mental retardation, short stature, and abnormally formed skeletal structure ■ In adults, lack of thyroid hormone results in lower metabolic rate, sluggishness, and myxedema (accumulation of fluid) ○ Hyperthyroidism: elevated rate of thyroid hormone secretion ■ Causes increased metabolic rate, extreme nervousness, chronic fatigue ■ Graves Disease: abnormal proteins produced by immune system similar in structure/function to TSH ● Causes bulging of the eyes → exophthalmia ○ Thyroid gland requires iodine to synthesize thyroid hormones ■ Iodine is taken up by thyroid hormones ● If lacking iodine, production/secretion of thyroid hormones decrease! ■ Number near T indicates how many iodine atoms there are ● Lack of iodine results in reduced T3 and T4 synthesis ○ Parafollicular cells of thyroid gland release calcitonin in addition to thyroid hormones ● PARATHYROID GLANDS (4) ○ Located in posterior wall of thyroid gland ○ Secrete parathyroid hormone (PTH) ■ Essential for helping to regulate blood calcium levels (more important than calcitonin) ■ Has many effects: 1. PTH binds to membrane-bound receptors of renal tubule cells, which increases active vitamin D formation. Vitamin D causes epithelial cells of intestine to increase calcium absorption a. (Vitamin D: skin → liver → kidneys) 2. PTH binds to receptors on osteoblasts. Substances released by osteoblasts increase osteoclast activity and cause resorption of bone tissue to release calcium into the circulatory system 3. PTH binds to receptors on cells of the renal tubules and decreases the rate at which calcium is lost in urine 4. PTH acts on its target tissues to raise blood calcium levels to normal ○ Hyperparathyroidism: high rate of PTH secretion ○ Soft bones, less excitable muscle/nerve cells (fatigue), kidney stones ○ Hypoparathyroidism: low rate of PTH secretion ○ Results from injury to or surgical removal of thyroid and parathyroid glands ○ Highly excitable muscle/nerve cells → spontaneous action potentials (cramps, tetanus) → respiratory muscles → breathing stops → death ● ADRENAL GLANDS (2) ○ Located superior to each kidney ○ Has an adrenal medulla (inner part) and adrenal cortex (outer part) ■ Inner and outer parts function as separate endocrine glands ○ Adrenal Medulla ■ Releases Epinephrine (Adrenaline) and small amounts of Norepinephrine ● Responses to sympathetic nervous system (becomes active when excited or physically active) → fight-or-flight response ○ Bind to membrane-bound receptors in target tissues ○ Major effects of the hormones released from Adrenal Medulla: 1. Increases in breakdown of glycogen to glucose in the liver, the release of glucose into the blood, and the release of fatty acids from adipose tissue. The glucose and fatty acids serve as energy sources to maintain body’s increases rate of metabolism 2. Increased heart rate, which increases blood pressure 3. Stimulation of smooth muscle in the walls of arteries supplying internal organs and skin, but NOT those supplying skeletal muscle. Blood flow to internal organs and skin decreases, which decreases function of internal organs. a. Blood flow to skeletal muscles increases 4. Increased blood pressure due to smooth muscle contraction in the walls of blood vessels in internal organs and skin 5. Increased metabolic rate of several tissues, especiall skeletal muscle, cardiac muscle, and nervous tissue (Regulation of Adrenal Medullary Secretions) ○ Responses from adrenal medulla reinforce effect of sympathetic/autonomic divisions of nervous system to prepare body for fight-or-flight/stress/physical activity ● ADRENAL CORTEX ○ Secretes 3 steroid hormones: mineralocorticoids, glucocorticoids, and androgens ○ Molecules of these steroid hormones enter target cells and bind to nuclear receptor molecules ○ Mineralocorticoids ■ Secreted by outer layer of adrenal cortex ■ Regulate blood volume and blood levels of K+ and Na+ ■ Aldosterone: major hormone of Mineralocorticoids ● Binds to receptor molecules in kidney, but also affects intestine, sweat glands, and salivary glands ● Causes Na+ and water to be retained ● Increases rate at which K+ is eliminated ● Rate of aldosterone secretion increases when blood K+ levels increase, or when blood Na+ levels decrease ● Blood pressure affects rate of aldosterone secretion ○ Renin (enzyme) is released from kidney due to low blood pressure ■ Causes Angiotensinogen to be converted to Angiotensin I which is converted by Angiotensin-Converting Enzyme into Angiotensin II ● Angiotensin II causes smooth muscle in blood vessels to constrict ● Increases aldosterone secretion ○ Aldosterone causes retention of Na+ and water, leading to increase in blood volume ■ All of this raises blood pressure! ○ Adrenal gland is VERY sensitive to changes in blood K+ levels ○ Glucocorticoids ■ Regulates blood nutrient levels ■ Cortisol: major hormone of Glucocorticoids ● Increases breakdown of proteins and lipids; increases their conversion to forms of usable energy ● Reduces inflammatory and immune responses ○ Cortisone → closely related steroid that reduces inflammation and immune responses from allergies, etc. ● Aids body by providing energy sources for tissues ○ If stressful conditions are prolonged however, immune system can be suppressed enough to make body susceptible to stress-related conditions ■ Adrenocorticotropic hormone (ACTH) from anterior pituitary bind to membrane-bound receptors and regulate secretion of cortisol from adrenal cortex ○ Androgens ○ Stimulate development of male sexual characteristics ○ Small amounts are secreted from adrenal cortex in both males and females ■ In males, androgens are released by testes ■ In females, androgens influence female sex drive ● PANCREAS, INSULIN, AND DIABETES ○ Endocrine part of pancreas consists of Pancreatic Islets of Langerhans (dispersed throughout exocrine portion of pancreas) ■ Secretes insulin (Beta cells), glucagon (Alpha cells), and somatostatin (Delta cells) ● Regulate blood levels of nutrients, especially glucose ○ If blood glucose levels are too low, lipids and proteins are broken down for energy → acidosis due to buildup of ketones ○ If blood glucose levels are too high, large volume of urine containing high amounts of glucose is produced by kidneys → dehydration ○ Insulin ■ Released by beta cells due to high glucose levels ■ Target tissues for insulin are liver, adipose tissue, muscles, and satiety center of hypothalamus ■ Binds to membrane-bound receptors → increases rate of glucose and amino acid uptake in these tissues ■ Diabetes Mellitus ● Type 1 Diabetes Mellitus: occurs when too little insulin is released from pancreas ○ Tissues cannot take up glucose effectively → hyperglycemia ○ Exaggerated appetite since glucose cannot be taken up by the satiety center of hypothalamus ○ Excess glucose in blood is excreted in urine → dehydration ○ Lipids and proteins are broken down to provide energy source for metabolism → body tissues are destroyed → acidosis, ketosis ○ Lack of energy ○ Insulin must be injected to control blood glucose levels! ● Type 2 Diabetes Mellitus: occurs when insufficient number of insulin receptors on target cells, or by defective receptors that do not respond to insulin ○ Glucagon ■ Released from alpha cells when glucose levels are low ■ Binds to membrane-bound receptors in liver to cause glycogen to convert to glucose ● Glucose is released from liver into blood to increase blood glucose levels ■ After a meal, when blood glucose levels are high, glucagon secretion is reduced ○ Somatostatin ■ Released by delta cells in response to food intake ■ Inhibits secretion of insulin and glucagon and inhibits gastric tract activity ● TESTES AND OVARIES ○ Secrete sex hormones that assist in developing sex characteristics ○ Testes produce sperm cells, ovaries produce oocytes ○ Testosterone ■ Main sex hormone of a male, secreted by testes ■ Responsible for growth/development of male reproductive structures, muscle enlargement, growth of body hair, voice changes, and male sex drive ○ Estrogen & Progesterone ■ Main sex hormones of female, secreted by ovaries ■ Contribute to development/function of female reproductive structures, growth of breasts, distribution of adipose tissue ● Also cyclically controls female menstrual cycle ○ LH and FSH stimulate secretion of hormones from ovaries and testes ■ Releasing hormone from hypothalamus controls rate of LH and FSH secretion ○ Hormones secreted by ovaries/testes have negative-feedback effect on hypothalamus and anterior pituitary ● THYMUS ○ Assists in immune system function ○ Secretes Thymosin → aids in development of white blood cells (T Cells) ■ Protect body against infection from foreign organisms ● PINEAL GLAND ○ Produces Melatonin → decreases secretion of LH and FSH by decreasing release of hypothalamicreleasing hormones ■ Inhibits functions of reproductive system ● Other Hormones ○ Cells in the lining of the stomach and small intestine secrete hormones that stimulate productive of digestive juices from stomach, pancreas, and liver ■ Hormones released from small intestine also help regulate rate at which food passes from stomach into small intestine ○ Prostaglandins ■ Function as intracellular signals (autocrine or paracrine chemical signals) → effects occur in tissues in which they are produced ■ Some cause relaxation of smooth muscle ■ Some cause contraction of smooth muscle, like the uterus during birth → have been used to initiate abortion ■ Play a role in inflammation to localize swelling/pain ● Needed for blood clotting ○ Erythropoietin ■ Released by kidneys in response to reduced oxygen levels in kidney ■ Acts on bone marrow to increase the production of red blood cells ○ Estrogen, Progesterone, Human Chorionic Gonadotropin ■ Stored in placenta (source of hormones that maintain pregnancy and stimulate breast development) ● Effects of Aging on the Endocrine System ○ Gradual decrease in secretion of some endocrine glands ○ GH secretion decreases whilst aging and lack of exercise ■ Decrease in bone/muscle mass, increase in adipose tissue ○ Melatonin secretion decreases ○ Thyroid hormone secretion decreases ○ Renin secretion from kidneys decrease ■ Reduces ability to respond to decreases in blood pressure ○ Reproductive hormone secretion decreases ■ Menopause in women ○ Thymosin secretion from thymus decreases ■ Smaller amount of lymphocytes → less effective immune system ○ PTH secretion increases to maintain blood calcium levels ■ Decrease in bone matrix ○ Higher tendency to develop Type 2 Diabetes Mellitus due to aging and weight gain
