Endocrine System (1) PDF

Endocrine System Overview Endocrine system: One of the two major control systems of the body; composed of glands and cells that secrete hormones. Nervous system: The other important control system of the body. Hormones: Chemical signals secreted into the plasma of the blood, re...

Endocrine System Overview Endocrine system: One of the two major control systems of the body; composed of glands and cells that secrete hormones. Nervous system: The other important control system of the body. Hormones: Chemical signals secreted into the plasma of the blood, regulating homeostasis. Hormones are secreted in response to: ○ Humoral stimuli: Changes in blood levels of ions and nutrients. ○ Neural stimuli: Nerve fibers stimulate hormone release. ○ Hormonal stimuli: Hormones stimulate other endocrine organs to release hormones. Target cells: Cells where hormones travel through blood plasma to regulate various body functions. Main Regulatory Functions of the Endocrine System 1. Regulation of metabolism: ○ Controls the rate of nutrient utilization and energy production. 2. Control of food intake and digestion: ○ Regulates feelings of satiation (fullness) and the breakdown of food into individual nutrients. 3. Modulation of tissue development: ○ Regulates the development of tissues, particularly the nervous system. 4. Regulation of ion levels: ○ Monitors blood pH, Na⁺, K⁺, and Ca²⁺ concentrations in the blood. 5. Control of water balance: ○ Regulates water balance by controlling the solute concentration in the blood. 6. Changes in heart rate and blood pressure: ○ Regulates heart rate and blood pressure, preparing the body for physical activity. 7. Control of blood glucose and other nutrients: ○ Regulates glucose and nutrient levels in the blood. 8. Control of reproductive functions: ○ Regulates the development and functions of the male and female reproductive systems. 9. Stimulation of uterine contractions and milk release: ○ Regulates uterine contractions during childbirth and stimulates milk release from the breasts in lactating females. 10. Modulation of immune system function: ○ Controls the production of immune cells. Disorders of the Endocrine System  Hypersecretion: Excessive hormone production. Hyposecretion: Insufficient hormone production. Summary The endocrine system plays a critical role in maintaining homeostasis by controlling various body functions such as metabolism, ion levels, water balance, heart rate, blood glucose levels, reproductive functions, and immune system modulation. Pituitary Gland and Hypothalamus Overview Endocrine system works with the nervous system to maintain homeostasis. Key structures: ○ Pituitary gland (hypophysis): Secretes 9 major hormones regulating body functions and other endocrine glands. ○ Hypothalamus: Regulates pituitary gland in response to hormones, sensory information, and emotions. Structure of the Pituitary Gland Location: Connected to the base of the brain, just below the hypothalamus, and rests in the sella turcica of the sphenoid bone. Size: 1 cm in diameter, 0.5–1.0 g (pea-sized). Connected by: Infundibulum (stalk of tissue) to the hypothalamus. Divided into: 1. Posterior pituitary (neurohypophysis): Continuous with the hypothalamus; forms from brain outgrowth. 2. Anterior pituitary (adenohypophysis): Derived from glandular epithelium (oral cavity). Posterior Pituitary (Neurohypophysis) Derived from an outgrowth of the hypothalamus during embryonic development. Hormones produced by the hypothalamus, stored in the posterior pituitary: ○ Neuropeptides/neurohormones: Released from neurons of the hypothalamus, transported through the hypothalamohypophysial tract. Anterior Pituitary (Adenohypophysis) Derived from epithelial tissue (not neural). Develops from the pituitary diverticulum (Rathke pouch) in the embryonic oral cavity. Thin band of tissue, pars intermedia, at the border with posterior pituitary (non-functional in adults). Hormones are traditional (not neuropeptides) and regulated by the hypothalamus. Relationship of the Pituitary Gland to the Hypothalamus Posterior pituitary regulation: ○ Via hypothalamohypophysial tract (neural pathway). ○ Hormones produced by neurons in the hypothalamus, stored in the posterior pituitary, released into the circulatory system upon stimulation. Anterior pituitary regulation: ○ Via hypothalamohypophysial portal system (blood vessel pathway).  ○ Hypothalamus secretes releasing/inhibiting hormones into a capillary bed that travels to the anterior pituitary, regulating its hormone secretion. Hypothalamic Control of the Posterior Pituitary 1. Neurons in the hypothalamus stimulate the secretion of posterior pituitary hormones. 2. Action potentials conducted along axons of hypothalamic neurons through the hypothalamohypophysial tract to the posterior pituitary. 3. Hormones stored in the posterior pituitary are released into circulation. 4. Hormones influence their target tissues via the circulatory system. Hypothalamic Control of the Anterior Pituitary 1. Neurons in the hypothalamus produce neuropeptides (releasing/inhibiting hormones) and secrete them into a capillary bed. 2. These hormones travel through the hypothalamohypophysial portal system to the anterior pituitary. 3. The neuropeptides bind to receptors on anterior pituitary cells, regulating hormone secretion. 4. Hormones secreted from the anterior pituitary enter the bloodstream and travel to target tissues. Hypothalamic Hormones Releasing hormones: Stimulate secretion of anterior pituitary hormones. Inhibiting hormones: Decrease secretion of anterior pituitary hormones. Pituitary Gland Hormones Posterior Pituitary (Neurohypophysis) Hormones: 1. Antidiuretic hormone (ADH): ○ Target: Kidneys. ○ Effect: Increases water reabsorption (reduces urine output). 2. Oxytocin: ○ Targets: Uterus, mammary glands. ○ Effects: Increases uterine contractions during birth, milk ejection from mammary glands. Anterior Pituitary (Adenohypophysis) Hormones: 1. Growth hormone (GH): ○ Target: Most tissues. ○ Effects: Promotes tissue growth, protein synthesis, fat breakdown, increases blood glucose levels, and IGF production. 2. Thyroid-stimulating hormone (TSH): ○ Target: Thyroid gland. ○ Effect: Increases thyroid hormone secretion. 3. Adrenocorticotropic hormone (ACTH): ○ Target: Adrenal cortex. ○ Effect: Increases glucocorticoid hormone secretion. 4. Lipotropins: ○ Target: Adipose tissue. ○ Effect: Increases lipid breakdown. 5. β-Endorphins: ○ Target: Brain. ○ Effects: Analgesia in the brain, inhibits GnRH secretion. 6. Melanocyte-stimulating hormone (MSH): ○ Target: Melanocytes in skin. ○ Effect: Increases melanin production (darkens skin), memory functions in the CNS. 7. Luteinizing hormone (LH): ○ Targets: Ovaries (females), testes (males). ○ Effects: Ovulation and progesterone production in females, testosterone synthesis and sperm production in males. 8. Follicle-stimulating hormone (FSH): ○ Targets: Follicles in ovaries (females), seminiferous tubules (males). ○ Effects: Follicle maturation, estrogen secretion (females); sperm cell production (males). 9. Prolactin: ○ Targets: Ovaries, mammary glands. ○ Effects: Milk production (females), enhances LH/FSH response, unclear reproductive function in males, roles in ion balance and immune regulation. Hormones of the Pituitary Gland The pituitary gland secretes hormones divided into two categories: 1. Posterior pituitary hormones 2. Anterior pituitary hormones Hormones from the pituitary gland have various effects on the body, and abnormal secretion can have major consequences. Posterior Pituitary Hormones The posterior pituitary is made up of neural tissue and stores/secretes two neuropeptides: 1. Antidiuretic Hormone (ADH) 2. Oxytocin Each hormone is secreted by a separate population of neurons. Antidiuretic Hormone (ADH) Function: Water conservation hormone that prevents the output of large amounts of urine (diuresis). Alternate name: Vasopressin (due to blood vessel constriction and increased blood pressure when large amounts are released). Synthesis: ADH is synthesized by neurosecretory neuron cell bodies in the hypothalamus (supraoptic nuclei) and stored in the posterior pituitary. Release Mechanism: ○ Action potentials in supraoptic neurons trigger ADH release into the blood. ○ ADH acts on kidney tubules, promoting water reabsorption, reducing urine volume, and maintaining blood osmolality and volume. Regulation: ○ Changes in blood osmolality and volume regulate ADH secretion. ○ Osmoreceptors detect blood osmolality, and baroreceptors detect blood pressure changes. ○ Increase in osmolality or decrease in blood pressure stimulates ADH release, increasing water reabsorption. ○ Decrease in osmolality reduces ADH secretion, leading to increased urine output. ○ Blood pressure changes also influence ADH secretion, with a drop in blood pressure triggering more ADH release. Effect on Urine: ADH adjusts urine concentration based on water consumption, maintaining blood osmolality and volume. Oxytocin  Function: Important reproductive hormone. Synthesis: Oxytocin is synthesized in hypothalamic neurosecretory neurons (paraventricular nuclei) and stored in the posterior pituitary. Actions: ○ Stimulates uterine contractions during labor, menstruation, and sexual intercourse. ○ Facilitates sperm movement and milk letdown in breastfeeding mothers. ○ Associated with maternal nurturing and bonding. Regulation: ○ Stretch of the uterus, stimulation of the cervix, and nipple stimulation trigger oxytocin release. ○ Action potentials travel from sensory neurons to the hypothalamus and posterior pituitary, where oxytocin is released into the blood. ○ Oxytocin increases uterine contractions and milk letdown. Anterior Pituitary Hormones The anterior pituitary hormones are synthesized by cells within the gland. Secretion is regulated by hypothalamic releasing and inhibiting hormones. Hormones secreted from the anterior pituitary are proteins, glycoproteins, or polypeptides. Growth Hormone (GH) Function: Stimulates growth in most tissues and regulates metabolism. Actions: ○ Increases amino acid uptake into cells, promotes protein synthesis, and decreases protein breakdown. ○ Increases lipolysis (breakdown of lipids) and release of fatty acids for energy use. ○ Increases glucose synthesis by the liver and reduces glucose usage in other tissues. ○ Stimulates production of insulin-like growth factors (IGFs), which promote bone and muscle growth. Regulation: ○ Growth hormone–releasing hormone (GHRH) stimulates GH secretion. ○ Growth hormone–inhibiting hormone (GHIH) (somatostatin) inhibits GH secretion. ○ GH secretion increases with stress or low blood glucose. ○ GH levels peak during deep sleep. Prolactin (PRL) Function:  ○ Promotes milk production in lactating females. ○ May enhance progesterone secretion after ovulation. Regulation: ○ Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine), which inhibits PRL secretion. ○ Dopamine levels decrease to release PRL. Thyroid-Stimulating Hormone (TSH) Function: Stimulates the synthesis and secretion of thyroid hormones. Regulation: ○ Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates TSH secretion. ○ Negative feedback from thyroid hormones inhibits TSH and TRH release. Adrenocorticotropic Hormone (ACTH) Function: Stimulates the secretion of cortisol from the adrenal cortex. Derived from: Proopiomelanocortin (POMC), a large precursor protein, which also produces lipotropins, β-endorphins, and melanocyte-stimulating hormone (MSH). Regulation: ○ Stress increases ACTH secretion. ○ ACTH secretion increases cortisol release, regulating chronic stress. Lipotropins Function: Cause lipid breakdown and release of fatty acids into the blood. β Endorphins Function: Have analgesic (pain-relieving) effects, similar to opiates. Regulation: Stress and exercise increase β-endorphin secretion. Melanocyte-Stimulating Hormone (MSH) Function: Stimulates melanin deposition in the skin. Regulation: Not fully understood but may play a role in appetite and sexual behavior. Luteinizing Hormone (LH) & Follicle-Stimulating Hormone (FSH) Function: ○ LH and FSH regulate reproductive processes. ○ Stimulate production of gametes (sperm and eggs) and reproductive hormones (estrogen, progesterone, testosterone). Regulation: ○ Controlled by gonadotropin-releasing hormone (GnRH) from the hypothalamus. Thyroid Gland Overview: Hormones Synthesized and Secreted: ○ Triiodothyronine (T3) ○ Tetraiodothyronine (T4 or thyroxine) ○ Calcitonin Anatomy: ○ Composed of two lobes connected by a narrow band of thyroid tissue (isthmus). ○ Located lateral to the trachea, inferior to the larynx; isthmus lies across the anterior trachea. ○ Weight: Approximately 20 grams, highly vascular, darker red than surrounding tissues. Structure: ○ Contains follicles: small spheres with cuboidal epithelial cells; the center of follicles is filled with colloid, which stores thyroid hormones in the form of thyroglobulin. ○ Parafollicular cells (located between follicles) secrete calcitonin, which reduces calcium levels when elevated. Thyroid Hormones (T3 & T4): Secretion: ○ T3 and T4 secreted from thyroid follicles. ○ T4 accounts for 80% of thyroid hormone secretion, T3 for 10%. ○ T4 is the precursor of T3. Synthesis of T3 and T4: 1. Iodide ions (I–) are taken up by thyroid follicle cells via secondary active transport (sodium-iodide symporter, NIS). 2. Thyroglobulin synthesized within follicle cells. 3. Iodide ions diffuse into follicle lumen, oxidized to iodine (I), and bind to tyrosine residues of thyroglobulin by thyroid peroxidase. ○ If 1 iodine binds to tyrosine = monoiodotyrosine (MIT). ○ If 2 iodine atoms bind = diiodotyrosine (DIT). 4. In colloid, two DIT combine to form T4, or one MIT and one DIT combine to form T3. 5. T3 and T4 stored in thyroid follicles bound to thyroglobulin. 6. Thyroglobulin taken up by follicle cells through endocytosis. 7. Lysosomes break down thyroglobulin to release T3 and T4. 8. T3 and T4 secreted into capillaries and transported in blood. Transport in Blood:  75% of T3 and T4 bound to thyroxine-binding globulin (TBG); remaining bound to albumin and other proteins. T3 and T4 form a reservoir in circulation, maintaining hormone levels. T3 is more potent than T4 (40% of T4 converted to T3 in tissues). Mechanism of Action of T3 and T4: Lipid-soluble hormones: Bind to nuclear receptors in target tissues, influencing genes and stimulating protein synthesis. Affects nearly every tissue by regulating metabolism and cell growth/differentiation. Increased Metabolic Rate: ○ Increased glucose, lipid, and protein metabolism. ○ Increased heat production due to Na+–K+ pump activity and mitochondrial ATP synthesis. Growth and Maturation: ○ Essential for the growth of bones, teeth, hair, and nervous tissue. ○ Permissive role for growth hormone (GH) function. Effects of Hypo- and Hyperthyroidism: Hypothyroidism (Decreased T3 and T4): ○ Symptoms: Low metabolic rate, weight gain, low body temperature, dry skin, slow heart rate, sluggish movement, apathy, myxedema (swelling). ○ Developmental Impact: Neonatal hypothyroidism leads to developmental delays, short stature, and physical deformities. Hyperthyroidism (Increased T3 and T4): ○ Symptoms: High metabolic rate, weight loss, high body temperature, rapid heart rate, tremors, hyperactivity, exophthalmos (protruding eyes). ○ Developmental Impact: Growth abnormalities, increased metabolism leading to tissue changes. Regulation of Thyroid Hormone Secretion: TRH (Thyrotropin-releasing hormone) from the hypothalamus and TSH (Thyroid-stimulating hormone) from the anterior pituitary regulate T3 and T4 secretion. Negative Feedback: T3 and T4 inhibit TRH and TSH release to maintain homeostasis. Stress and Cold Exposure: Increases TRH secretion. Dietary Iodine Deficiency: Can lead to hypothyroidism and goiter. Calcitonin: Secreted by Parafollicular Cells in response to elevated blood calcium levels. Target Tissue: Bone; reduces osteoclast activity and promotes bone deposition. Functions: 1. Protects against hypercalcemia in infants and children. 2. Stimulates calcium and phosphate secretion by kidneys. 3. Inhibits parathyroid hormone (PTH) effects. Clinical Use: Calcitonin nasal spray used for postmenopausal osteoporosis management. 18.4 Parathyroid Glands: Key Points Location & Structure: ○ Usually embedded in the posterior part of the thyroid gland. ○ Composed of two cell types: chief cells (secrete parathyroid hormone, PTH) and oxyphils (function not fully understood). ○ Typically, four parathyroid glands are present. ○ Cells organized in densely packed masses (cords), not follicles. ○ In some cases, one or more glands remain in nearby connective tissue rather than being embedded in the thyroid. Parathyroid Hormone (PTH): ○ Crucial for regulating calcium levels in body fluids. ○ Major target tissues: Bone Kidneys Small intestine (indirectly by stimulating vitamin D activation). ○ PTH binds to membrane-bound receptors and activates G protein, increasing cAMP levels. Effects of PTH: ○ Bone: Stimulates osteoclast activity, increasing bone reabsorption, leading to a rise in blood calcium levels. Osteoclasts don't have PTH receptors; osteoblasts and bone marrow stem cells do. PTH binds to osteoblasts, promoting osteoclast activity. ○ Kidneys: Increases calcium reabsorption, reducing calcium loss in urine. Enhances active vitamin D3 formation in the kidneys. ○ Small Intestine: Vitamin D3 stimulates calcium absorption in intestinal epithelial cells. PTH increases active vitamin D3 synthesis, raising calcium and phosphate absorption. Phosphate Regulation: ○ PTH increases phosphate release from bone and stimulates its absorption in the small intestine. ○ However, PTH increases phosphate excretion in the kidneys. ○ The overall effect is to decrease blood phosphate levels to avoid calcium phosphate precipitation, which could cause soft tissue irritation and inflammation. PTH Secretion Regulation: ○ Triggered by low blood calcium (Ca²⁺) levels. ○ Inhibited by elevated blood calcium levels. ○ This maintains blood calcium within a normal range. Effects of PTH Imbalance: ○ Hypoparathyroidism (Hyposecretion of PTH):  Commonly caused by accidental removal during thyroid surgery. Results in hypocalcemia (low blood calcium). Symptoms: increased neuromuscular excitability, tetany, laryngospasm, potential death from asphyxiation, flaccid heart muscle, cardiac arrhythmia, diarrhea. ○ Hyperparathyroidism (Hypersecretion of PTH): Primary: Due to abnormal parathyroid function (90% adenomas, 9% idiopathic hyperplasia, 1% carcinoma). Secondary: Due to conditions lowering blood calcium levels (poor diet, vitamin D deficiency, pregnancy, lactation). May cause hypercalcemia (high blood calcium) or normal calcium levels. Symptoms: Calcium deposits in kidneys (kidney stones), lungs, blood vessels, and gastric mucosa. Weakened bones due to calcium reabsorption. Neuromuscular system becomes less excitable (muscular weakness). Increased force of heart contractions; high blood calcium levels can cause cardiac arrest during contraction. Constipation. Consequences of Hypocalcemia: ○ Inactive parathyroid glands can lead to hypocalcemia. ○ Low calcium increases Na+ channel activity, causing depolarization. ○ Symptoms: nervousness, muscle spasms, cardiac arrhythmia, convulsions, possible death from tetany (including respiratory muscles). Adrenal Glands Overview Location: Near superior poles of kidneys, behind peritoneum, surrounded by adipose tissue. Structure: ○ Enclosed by connective tissue capsule. ○ Well-developed blood supply. ○ Composed of an inner medulla and an outer cortex, derived from separate embryonic tissues. Blood supply: Trabeculae of connective tissue penetrate the gland, supplying blood. Adrenal Medulla Origin: Arises from neural crest cells (same as sympathetic postganglionic neurons). Structure: Closely packed polyhedral cells in the center of the gland. Hormones: ○ Epinephrine (80%) and Norepinephrine (20%). ○ Both bind to adrenergic receptors (α and β receptors). Effects of Epinephrine and Norepinephrine: ○ Prepare body for physical activity (fight-or-flight response). ○ Increase heart rate and contraction force. ○ Blood vessel constriction in skin, kidneys, and gastrointestinal tract. ○ Blood vessel dilation in skeletal and cardiac muscles. ○ Metabolic effects of epinephrine: 1. Increases blood glucose by promoting glycogen breakdown in liver. 2. Increases glycogen breakdown in muscles (for internal use). 3. Increases lipid breakdown in adipose tissue, releasing fatty acids for energy use. Secretion Process of Adrenal Medullary Hormones 1. Stress, physical activity, or low blood glucose stimulate the hypothalamus. 2. Sympathetic nervous system activity increases, leading to adrenal medulla stimulation. 3. Adrenal medulla secretes epinephrine and norepinephrine. Adrenal Cortex Layers: Three distinct layers, each secreting a different hormone type. 1. Zona Glomerulosa - secretes Mineralocorticoids (mainly aldosterone). 2. Zona Fasciculata - secretes Glucocorticoids (mainly cortisol). 3. Zona Reticularis - secretes Androgens. Hormones are lipid-soluble (derived from cholesterol) and diffuse from cells as they are synthesized. Transport: Bound to plasma proteins in blood. Mineralocorticoids (e.g., Aldosterone) Function: Regulate ion balance. ○ Increases sodium (Na+) reabsorption and potassium (K+) excretion by kidneys. ○ Increases water reabsorption, raising blood pressure. ○ Stimulates hydrogen ion (H+) excretion, preventing alkalosis. Glucocorticoids (e.g., Cortisol) Functions: ○ Metabolic: Increase lipid and protein breakdown. Stimulate gluconeogenesis (glucose production) and increase blood glucose levels. ○ Developmental: Aid in tissue maturation and receptor development for epinephrine and norepinephrine. ○ Anti-inflammatory: Suppress immune response by reducing white blood cells and inflammatory chemicals. Regulation: ○ Controlled by ACTH from the anterior pituitary. ○ CRH (Corticotropin-releasing hormone) from the hypothalamus stimulates ACTH release. ○ Stress and low blood glucose trigger increased secretion of CRH and cortisol. Adrenal Androgens Function: Weak androgens that promote pubic and axillary hair growth and sex drive in females. Converted to testosterone in peripheral tissues. Effects in males are negligible compared to testosterone from testes. Hormone Abnormalities Hypersecretion or hyposecretion of adrenal hormones can result in various disorders (discussed in detail in later chapters). Pancreas Overview The pancreas functions as both an exocrine gland (produces pancreatic juice) and an endocrine gland (secretes hormones). Exocrine portion: Acini produce pancreatic juice carried to the small intestine by a duct system. Endocrine portion: Consists of pancreatic islets (islets of Langerhans), which secrete hormones into the bloodstream. Located behind the peritoneum between the stomach’s greater curvature and the duodenum. Size: About 15 cm long and 85–100 grams in weight. The head of the pancreas lies near the duodenum, and the body and tail extend toward the spleen. Pancreatic Islets (Islets of Langerhans) Composed of 500,000 to 1 million islets. Cell types: 1. Alpha (α) cells (20%): Secrete glucagon (peptide hormone). 2. Beta (β) cells (75%): Secrete insulin (peptide hormone with two peptide chains). 3. Delta (δ) cells: Secrete somatostatin (peptide hormone). Islets are surrounded by a capillary network and are innervated by the autonomic nervous system. Effect of Insulin and Glucagon on Target Tissues The pancreatic hormones regulate blood nutrient levels, especially glucose and amino acids. Insulin's target tissues: 1. Liver 2. Adipose tissue 3. Skeletal muscle 4. Satiety center in the hypothalamus, which controls appetite. Insulin Function Primary function: Lowers blood glucose levels by stimulating glucose transport into cells. Secretion: Occurs when blood glucose levels are elevated (e.g., after a meal). Insulin binds to receptors on target cells, causing the phosphorylation of membrane proteins and increasing the number of transport proteins for glucose and amino acids. The target tissue responds by increasing glucose and amino acid uptake for energy, glycogen, or lipid synthesis (adipose tissue).  Without insulin, glucose and amino acid uptake decreases significantly, leading to elevated blood glucose levels (e.g., in diabetes). High blood glucose causes: ○ Polyphagia: Intense hunger despite high glucose levels. ○ Polyuria: Increased urine volume due to glucose filtering into kidney tubules, leading to water loss. ○ Polydipsia: Increased thirst due to elevated blood osmolality. Effects of Excess and Deficiency in Insulin Excess insulin: Causes rapid glucose uptake, leading to low blood glucose levels, which can affect the nervous system, causing dizziness, cognitive issues, or loss of consciousness. Insulin is vital for normal blood glucose regulation. Glucagon Function Companion hormone to insulin: Secreted when blood glucose levels drop. Promotes the release of glucose from intracellular stores, primarily in the liver. Increases glycogen breakdown (glycogenolysis) and glucose production (gluconeogenesis) in the liver. Increases lipid breakdown (lipolysis) in adipose tissue. Hormones of the Pancreas (Summary) Glucagon (alpha cells): ○ Acts on the liver to increase glucose production and release. ○ Increases glycogen breakdown and glucose synthesis. Insulin (beta cells): ○ Acts on the liver, skeletal muscle, adipose tissue. ○ Increases glucose and amino acid uptake and utilization. Somatostatin (delta cells): ○ Inhibits insulin and glucagon secretion. Regulation of Pancreatic Hormones Insulin Secretion Increased by: 1. Hyperglycemia (high blood glucose levels). 2. Certain amino acids. 3. Parasympathetic stimulation (food intake). 4. Gastrointestinal hormones (gastrin, secretin, cholecystokinin). Decreased by:  1. Hypoglycemia (low blood glucose levels). 2. Sympathetic stimulation, which maintains glucose levels during physical activity. 3. Somatostatin, which inhibits insulin and glucagon secretion. Glucagon Secretion Increased by: ○ Low blood glucose levels. ○ Amino acids. ○ Sympathetic stimulation (physical activity). After a high-protein meal: Both insulin and glucagon secretion increase. ○ Insulin promotes amino acid uptake for protein synthesis. ○ Glucagon stimulates glucose synthesis from amino acids. Effects of Insulin and Glucagon on Target Tissues (Detailed) 1. Skeletal muscle, cardiac muscle, cartilage, bone, fibroblasts, leukocytes, mammary glands: ○ Insulin: Increases glucose uptake and glycogen synthesis. ○ Glucagon: Little effect (skeletal muscle lacks glucagon receptors). 2. Liver: ○ Insulin: Increases glycogen synthesis and glucose use for energy (glycolysis). ○ Glucagon: Rapid glycogen breakdown and glucose release, increased gluconeogenesis. 3. Adipose cells: ○ Insulin: Increases glucose uptake, glycogen and lipid synthesis, fatty acid uptake. ○ Glucagon: At high concentrations, promotes lipid breakdown. 4. Nervous system: ○ Insulin: Increases glucose uptake in the satiety center. ○ Glucagon: No significant effect. 18.7 Hormonal Regulation of Nutrient Utilization After a Meal (Under Resting Conditions): Decreased secretion of: ○ Glucagon ○ Cortisol ○ Growth hormone (GH) ○ Epinephrine Increased secretion of insulin: ○ Due to increased blood glucose and parasympathetic stimulation. ○ Effect of insulin: Increases uptake of glucose, amino acids, and lipids by target tissues. Substances not used for metabolism are stored. Glucose: Converted to glycogen in skeletal muscle and liver. Used for lipid synthesis in adipose tissue and liver. Amino acids: Incorporated into proteins. Lipids: Stored in adipose tissue and liver. ○ High protein meals: Small glucagon secretion increases liver's use of amino acids for glucose production. 1–2 Hours After a Meal: Absorption of nutrients declines. Blood glucose levels decline. Secretion increases for: ○ Glucagon ○ GH ○ Cortisol ○ Epinephrine Insulin secretion decreases: ○ Slows glucose entry into target tissues. ○ Stored glycogen: Converted back to glucose for energy. ○ Liver: Releases glucose into the blood. ○ Other tissues: Start using lipids and proteins for energy. ○ Adipose tissue: Releases fatty acids. ○ Liver: Releases triglycerides (in lipoproteins) and ketones into the blood. ○ Energy source: Lipids become the major energy source for most tissues when blood glucose is low. Negative Feedback Mechanism: When blood glucose is high:  ○ Hormones (insulin, GH, glucagon, epinephrine, cortisol) increase uptake and storage of glucose, amino acids, and lipids. When blood glucose is low: ○ These hormones release glucose, shifting energy source to lipids and proteins for most tissues. During Exercise: Increased demand for energy in skeletal muscles. Initial energy source: Intracellular nutrients sustain muscle contraction for a short time. During prolonged activity: ○ Sympathetic nervous system activation: Increases release of: Epinephrine (from adrenal medulla) Glucagon (from pancreas) ○ Epinephrine and glucagon: Convert glycogen to glucose in the liver. Release glucose into the blood for muscle energy. Short half-lives allow for rapid adjustment of blood glucose levels. Prolonged Sustained Activity: Glucose from the liver becomes insufficient to maintain blood glucose levels for brain function. Insulin decreases: ○ Prevents glucose uptake by most tissues, conserving it for the brain. Epinephrine, glucagon, cortisol, GH: ○ Increase fatty acids, triglycerides, and ketones in the blood. ○ GH increases protein synthesis and slows protein breakdown. ○ Glucose metabolism decreases. ○ Skeletal muscles shift to lipid metabolism for energy. ○ End of long exercise: Muscles rely more on lipid metabolism for energy. 18.9 Hormones of the Pineal Gland Location: Pineal gland is located in the epithalamus of the brain. Primary function: Secretes hormones that act on the hypothalamus and gonads to inhibit reproductive functions. Key secretory products: 1. Melatonin: Can decrease hypothalamic GnRH secretion. May inhibit reproductive functions. Helps regulate sleep cycles by increasing the tendency to sleep. 2. Arginine vasotocin: Works with melatonin to regulate reproductive system in some animals. Inhibits GnRH secretion. Regulation of Pineal Secretions: Light and dark cycles regulate melatonin secretion: ○ Light enters the eye, stimulating neurons in the retina. ○ Action potentials are transmitted to the hypothalamus. ○ Action potentials from the hypothalamus are transmitted through the sympathetic division to the pineal gland. ○ Darkness: Increases sympathetic stimulation to the pineal gland and increases melatonin secretion. ○ Light: Decreases sympathetic stimulation and melatonin secretion. Melatonin’s effects: ○ Inhibits GnRH secretion from the hypothalamus. ○ May regulate sleep cycles. ○ Secretion increases at night, decreases during the day. Effect on reproductive system: ○ Animals that breed in spring experience reduced pineal secretion with longer daylight, leading to reproductive hypertrophy in summer. ○ In humans, melatonin's role in reproductive function is unclear, but supplemental melatonin may affect reproductive systems. Pineal gland dysfunction: ○ Tumors destroying the pineal gland correlate with early sexual development. ○ Tumors increasing pineal hormone secretion correlate with delayed reproductive system development. ○ It is unclear if the pineal gland controls puberty onset. 18.10 Other Hormones and Chemical Messengers Hormones of the Thymus:  Thymus location: Neck and superior to the heart. Hormone: Thymosin ○ Role in development and maturation of the immune system. Hormones of the Digestive Tract: Several hormones regulate digestive functions by influencing the activity of the stomach, intestines, liver, and pancreas. Hormones of Adipose Tissue: Hormone: Leptin ○ Secreted by adipocytes. ○ Regulates satiety signals in the hypothalamus. ○ Disables synthesis of leptin leads to excessive eating and obesity. Hormonelike Chemicals: Autocrine chemical messengers: ○ Released from cells and influence the same cell. Paracrine chemical messengers: ○ Released from one cell type, diffuse short distances, and influence target cells nearby. Examples of autocrine/paracrine messengers: ○ Eicosanoids: Derived from arachidonic acid, includes: Prostaglandins Thromboxanes Prostacyclins Leukotrienes ○ Released from injured cells, involved in inflammation and other processes (e.g., uterine contractions, coagulation). Prostaglandins: ○ Involved in pain sensation, vasodilation (linked to headaches). ○ Inhibited by anti-inflammatory drugs (e.g., aspirin). Endogenous analgesics: ○ Include enkephalins, endorphins, and dynorphins. ○ Act on the same receptors as morphine. ○ Produced in the brain, pituitary gland, spinal cord, intestines. ○ Moderate pain sensation and increase during exercise and stress. Growth factors: ○ Epidermal growth factor: Stimulates cell division and important for embryonic development. ○ Interleukin-2: Stimulates T lymphocyte proliferation, crucial for immune responses. Summary: Hormonelike chemicals and messengers play complex roles in regulating various bodily functions, often through autocrine and paracrine actions. Understanding these chemical messengers aids in the development of treatments for various diseases.