The Endocrine System Chapter 46

Types of Chemical Messengers A hormone is a chemical that is secreted into extracellular fluid and carried by the blood -Can therefore act at a distance from source -Only targets with receptor can respond Paracrine regulators do not travel in blood -Allow cells of organ to regulate each other Pheromones are chemicals released into the environment to communicate among individuals of a single species

Types of Chemical Messengers Some neurotransmitters are distributed by the blood and act as neurohormones -Norepinephrine coordinates the activity of heart, liver and blood vessels during stress Hormone production and release is often regulated directly or indirectly by the nervous system

Hormones carried by blood Axon Neurotransmitters Glands Paracrine secretion Hormones carried by blood Target cell Extracellular space Receptor proteins Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Endocrine System The endocrine system includes all the organs and tissues that produce hormones -Includes endocrine glands, which are specialized to secrete hormones -Also organs, like the liver, that secrete hormones in addition to other functions Exocrine glands secrete their products, such as saliva or milk, into a duct for transport to the outside

Parathyroid glands (behind thyroid) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovaries (in females) Parathyroid glands (behind thyroid) Hypothalamus Pineal gland Neurohypophysis Pituitary gland Thyroid gland Thymus Adrenal glands Pancreas Testes (in males) Adenohypophysis

Classes of Hormones Molecules that function as hormones must exhibit two basic characteristics 1. Must be sufficiently complex to convey regulatory information to their target cells 2. Must be adequately stable to resist destruction before reaching their target cells Three chemical classes meet these requirements

Classes of Hormones 1. Peptides and proteins -Glycoproteins 2. Amino acid derivatives -Catecholamines -Thyroid hormones -Melatonin 3. Steroids -Sex steroids -Corticosteroids

Classes of Hormones Hormones may be categorized as: -Lipophilic (nonpolar) = fat-soluble -Steroid hormones and thyroid hormones -Bind to intracellular receptors -Hydrophilic (polar) = water-soluble -All other hormones -Bind to extracellular receptors

Lipophilic Hydrophilic 1. Hormones 2. Hormones 3. Nontarget 5 3 4 1 2 Lipophilic Hydrophilic Endocrine gland A Endocrine gland B 1. Hormones secreted into extracellular fluid and diffuse into 2. Hormones distributed by blood to all cells. Diffuse from blood to extracellular fluid. 3. Nontarget cells lack receptors, and cell stimulation does not occur. 4. Target cells possess receptors, and are activated by hormones. 5. Unused, deactivated hormones are removed by the liver and kidney. Secretory vesicles Hormones Transport proteins Membrane receptors Target cell Activated Nuclear receptor Nontarget cells Extracellular fluid Blood vessels Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Paracrine Regulators Paracrine regulation occurs in most organs -Growth factors are proteins that promote growth and cell division in specific organs -Epidermal growth factor = Skin -Nerve growth factor = Neurons -Insulin-like growth factor = Bone -Cytokines = Immune system

Paracrine Regulators The endothelium of blood vessels is a rich source of paracrine regulators -Nitric oxide (NO) which promotes vasodilation -Endothelin which stimulates vasoconstriction -Bradykinin which promotes vasodilation

Paracrine Regulators Prostaglandins -A diverse group of fatty acids that are produced in almost every organ -Regulate a variety of functions including: -Smooth muscle contraction, lung function, labor, and inflammation -Synthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen

Lipophilic Hormones Lipophilic hormones include the steroid hormones (derived from cholesterol) and the thyroid hormones (tyrosine + iodine) -As well as the retinoids, or vitamin A Thyroxine Cortisol (Hydrocortisone) O HO OH H3C CH2OH C I NH2 CH2 COOH Testosterone CH

Lipophilic Hormones These hormones circulate in the blood bound to transport proteins -Dissociate from carrier at target cells -Pass through the cell membrane and bind to an intracellular receptor, either in the cytoplasm or the nucleus -Hormone-receptor complex binds to hormone response elements in DNA -Regulate gene expression

1. Hormone passes 2. Inside target 3. Hormone-receptor Blood plasma Protein Lipophilic hormones mRNA DNA Hormone response element 1. Hormone passes through plasma membrane 2. Inside target cell the hormone binds to a receptor protein in the cytoplasm or nucleus 3. Hormone-receptor complex binds to hormone response element on DNA, regulating gene transcription 4. Protein synthesis 5. Change in protein synthesis is cellular response Cytoplasm Plasma membrane Nucleus Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hydrophilic Hormones Hydrophilic hormones include the peptide, protein and catecholamine hormones -Too large or polar to cross cell membrane Hormones bind to extracellular receptors -Initiate signal transduction pathways 1. Activation of protein kinases 2. Production of second messengers

1. Receptors Function as Kinase Enzymes Hormone Inactive Active kinase domain Receptor Target protein P Phosphorylated GPCR Inactive G Active G Second messenger- generating enzyme Hormones GTP GDP protein kinase proteins Active Protein kinase Second messenger 1. Receptors Function as Kinase Enzymes 2. Receptors Activate G Proteins Cellular response g a b ADP ATP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hydrophilic Hormones Receptor kinases -For some peptide hormones (like insulin) the receptor itself is a kinase -Can directly phosphorylate intracellular proteins that alter cellular activity -For other peptide hormones (like growth hormone) the receptor itself is not a kinase -Rather, it activates intracellular kinases

Hydrophilic Hormones Second-messenger systems -Many hydrophilic hormones work through second messenger systems -Two have been described: -One involving cyclic adenosine monophosphate (cAMP) -One that generates 2 lipid messengers: inositol triphosphate (IP3) and diacyl glycerol (DAG)

Hydrophilic Hormones Second-messenger systems -Receptors are linked to a second-messenger-generating enzyme via membrane proteins called G proteins -Are thus called G-protein-coupled receptors (GPCP) -When the G protein activates the enzyme, the second-messenger molecules increase

The Pituitary Gland The pituitary gland is also known as the hypophysis -It hangs by a stalk from the hypothalamus The pituitary gland consists of two parts: -Anterior pituitary (adenohypophysis) -Appears glandular -Posterior pituitary (neurohypophysis) -Appears fibrous

The Posterior Pituitary The posterior pituitary develops from growth of the brain -It remains directly connected to the hypothalamus by a tract of axons It stores and releases two hormones, that are actually produced by neuron cell bodies in the hypothalamus -Neuroendocrine reflex

The Posterior Pituitary Antidiuretic hormone (ADH) -A peptide hormone that stimulates water reabsorption by the kidney, and thus inhibits diuresis (urine production) Oxytocin -Like ADH, it is composed of 9 amino acids -In mammals, it stimulates the milk ejection reflex and uterine contractions during labor, and it regulates reproductive behavior

ADH increases vasoconstriction ADH reduces urine volume Effector ADH synthesized by neurosecretory cells in the hypothalamus is released from neuro- hypophysis into blood Integrating Center Water returned to Response Increases blood pressure Osmotic concentration of blood increases Stimulus Dehydration Lowers blood volume and pressure Osmoreceptors in CNS monitor concentration Sensor Baroreceptors in aorta monitor pressure ( – ) Negative feedback Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

The Anterior Pituitary The anterior pituitary develops from a pouch of epithelial tissue of the embryo’s mouth It produces at least seven essential hormones -Collectively called tropic hormones or tropins -Can be categorized into three families -Peptide hormones, protein hormones and glycoprotein hormones

The Anterior Pituitary Peptide hormones -Fewer than 40 amino acids in size -Adrenocorticotropic hormone (ACTH) -Melanocyte-stimulating hormone (MSH) Protein hormones -A single chain of about 200 amino acid -Growth hormone (GH) -Prolactin (PRL)

The Anterior Pituitary Glycoprotein hormones -Dimers, containing alpha (a) and beta (b) subunits, each around 100 amino acids -Thyroid-stimulating hormone (TSH) -Luteinizing hormone (LH) -Follicle-stimulating hormone (FSH)

The Anterior Pituitary The activity of the anterior pituitary is controlled by hormones of the hypothalamus -Neurons secrete releasing hormones and inhibiting hormones, which diffuse into blood capillaries at the hypothalamus’ base -Each hormone delivered by the hypothalamohypophysial portal system regulates a specific anterior pituitary hormone

Secondary capillaries Neurohypophysis Primary capillaries Portal veins Hypothalamus Adenohypophysis Secondary capillaries Neurohypophysis Primary capillaries Primary capillaries Axons to primary Neuron cell bodies Hormones Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

The Anterior Pituitary The hypothalamus and the anterior pituitary are partially controlled by the very hormones whose secretion they stimulate -This is termed negative feedback or feedback inhibition Positive feedback is uncommon because it causes deviations from homeostasis -One example is the control of ovulation

Hypothalamus Adenohypophysis Target Glands Hormones Releasing hormones Tropic hormones (TSH, ACTH, FSH, LH) Adenohypophysis Thyroid, adrenal cortex, gonads Target Glands Hormones Releasing hormones (TRH, CRH, GnRH) Hypothalamus ( + ) Target cells ( – ) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Negative feedback

The Anterior Pituitary The anterior pituitary is sometimes referred to as the “master gland” -Its effects may be direct or indirect -Direct: activation of nonendocrine targets -Indirect: activation of other endocrine glands Hypophysectomy is the surgical removal of the pituitary

Anterior Pituitary Disorders Growth hormone stimulates growth of muscles and connective tissue -It also promotes the production of insulin-like growth factors -Stimulate cell division in the epiphyseal growth plates, and thus bone elongation Gigantism is caused by an excessive secretion of growth hormone in a child

Anterior Pituitary Disorders

Anterior Pituitary Disorders In contrast, pituitary dwarfism is caused by a deficiency in GH secretion during childhood GH can no longer cause an increase in height in adults because human skeletal plates transform from cartilage into bone at puberty -Excessive GH secretion in an adult results in acromegaly

The Thyroid Gland In humans, the thyroid gland is shaped like a bow tie, and lies just below the Adam’s apple in the front of the neck -It secretes: -Thyroid hormones -Thyroxine -Triiodothyronine -Calcitonin

The Thyroid Gland Thyroid hormones bind to nuclear receptors -Regulate carbohydrate & lipid metabolism -Adults with hypothyroidism have low production of thyroxine -Reduced metabolism and overweight -Adults with hyperthyroidism have high production of thyroxine -High metabolism and weight loss -Trigger metamorphosis in amphibians

rapid differentiation Thyroxine production –35 –30 –25 –20 –15 Days from emergence of forelimb –10 –5 +5 +10 +20 TSH stimulates thyroid to produce thyroxine. Forelimbs emerge. T ail is reabsorbed . Hypothalamus stimulates adenohypophysis to secrete TSH. Rapid growth Reduced growth, rapid differentiation Rapid differentiation Premetamorphosis Prometamorphosis Climax Receptor stimulation Hypothalamus stimulation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

The Thyroid Gland Calcitonin -A peptide hormone -Stimulates the uptake of calcium (Ca2+) into bones -Thus, lowering its levels in the blood

The Parathyroid Glands The parathyroid glands are four small glands attached to the thyroid -Produce parathyroid hormone (PTH) in response to falling levels of Ca2+ in blood -Stimulates osteoclasts to dissolve calcium phosphate crystals in the bone matrix and release Ca2+ into blood -Stimulates the kidneys to reabsorb Ca2+ from the urine

The Parathyroid Glands PTH also indirectly leads to the absorption of Ca2+ from food in the intestines by its activation of vitamin D -Vitamin D is produced in the skin from a cholesterol derivative in response to UV light -It diffuses into blood in an inactive form -Activated by an enzyme that is stimulated by PTH

Stimulus Parathyroid Effector Response Increased blood Ca2+ Low blood Ca2+ Stimulus Parathyroid glands Parathyroid Secretes PTH ( + ) ( – ) Osteoclasts dissolve Ca(PO4)2 crystals in bone, releasing Ca2+ Effector Reabsorption of Ca2+, excretion of PO43– absorption of Ca2+ from intestine (due to PTH activation of vitamin D) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Negative feedback

The Adrenal Glands The adrenal glands are located just above each kidney -Medulla = Inner portion -Stimulated by the sympathetic division of the autonomous nervous system -Cortex = Outer portion -Stimulated by the anterior pituitary, through the hormone ACTH

The Adrenal Glands The medulla secretes the catecholamines epinephrine and norepinephrine -These trigger “alarm” responses helping the body prepare for extreme efforts -Lead to an increase in: heart rate, blood pressure, blood glucose level, and blood flow to heart and muscle

The Adrenal Glands The cortex secretes steroid hormones called corticosteroids -Glucocorticoids (such as cortisol) maintain glucose homeostasis and modulate some aspects of the immune response -Mineralocorticoids (such as aldosterone) regulate mineral balance by stimulating the kidneys to reabsorb Na+ and excrete K+

Catecholamine Hormones Glucocorticoids Stimulus Sympathetic nervous system Sympathetic axons Adrenal medulla Adrenal cortex Adenohypophysis Effector Catecholamine Hormones Glucocorticoids ACTH secreted from the adenohypophysis Longer term stress response. ( + ) Stress Stimulus ( – ) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Effects on lipid and carbohydrate metabol- ism, immune system, and damage repair. Short term stress Effects on cardiovascular system, carbohydrate and lipid metabolism, central nervous system. Negative feedback

The Pancreas The pancreas is located adjacent to stomach -Connected to the duodenum of the small intestine by the pancreatic duct The islets of Langerhans are scattered clusters of cells throughout the pancreas -These govern blood glucose levels through two hormones with antagonistic functions

The Pancreas Insulin -Secreted by beta (b) cells of the islets -Stimulates cellular uptake of blood glucose and its storage as glycogen in the liver and muscle cells or as fat in fat cells Glucagon -Secreted by alpha (a) cells of the islets -Promotes the hydrolysis of glycogen in the liver and fat in adipose tissue

Stimulus After a Meal Between Meals Effector Response ( + ) ( – ) Blood glucose increased Stimulus Blood glucose decreased After a Meal Between Meals Effector Increased glucagon production by a cells Increased insulin by b cells Response Glycogen hydrolyzed to glucose, then secreted into blood, increasing blood glucose Glucose moves from blood into cells, reducing blood glucose Sensor Pancreatic Islets Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Negative Feedback

Diabetes Mellitus Diabetics cannot take up glucose from blood -Type I (insulin-dependent diabetes) -Individuals lack insulin-secreting b cells -Treated by daily injections of insulin -Type II (noninsulin-dependent diabetes) -Most patients have this form -Very low number of insulin receptors -Treated by diet and exercise

The Gonads The ovaries and testes in vertebrates -Produce sex steroids that regulate reproductive development -Estrogen and progesterone -“Female” hormones -Androgens -“Male” hormones -Testosterone and its derivatives

The Pineal Gland The pineal gland is located in the roof of the third ventricle of the brain -Functions as an endocrine gland by secreting the hormone melatonin -Reduces dispersal of melanin granules -Regulates biological clocks -Synchronizes various body processes to a circadian rhythm

Other Hormones Some hormones are secreted by organs that are not exclusively endocrine glands -Atrial natriuretic hormone is secreted by the right atrium of the heart -Promotes salt and water excretion -Erythropoietin is secreted by the kidney -Stimulates the bone marrow to produce red blood cells

Insect Hormones Insects undergo two types of transformations during post-embryonic development -Molting = Shedding of old exoskeleton and secretion of a new larger one -Metamorphosis = Radical transformation from the larval to the adult form

Insect Hormones Hormonal secretions influence both molting and metamorphosis -Brain hormone stimulates prothoracic gland to produce ecdysone, or molting hormone -High levels cause molting -The corpora allata produce a hormone called the juvenile hormone -Low levels result in metamorphosis

Neurosecretory cells Larval molt Pupal molt Adult molt Corpora allata Prothoracic gland Brain hormone Juvenile hormone Ecdysone Low amounts Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.