Internal Signaling of the Body The Endocrine System Internal Signaling of the Body Hypothalamus Pineal gland Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas Ovary (female) Testis (male)

“Endocrine” = internal secretions Similar in most vertebrates Works with the nervous system to control the body.

Types of Signaling Molecules Neurotransmitters – local signals released by axons Hormones – travel through the blood stream Pheromones – act on OTHER organisms Travel through air, water, etc.

diffuses across synapse Local Signaling (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling

Hormones Are secreted by endocrine glands. Travel through the blood stream. Bind with receptors on or in target cells. Induce the cell to make changes.

Two Main Categories of Hormones: Steroid hormones Secreted by the adrenal glands and gonads Peptide hormones

Steroid Hormones Are lipids (hydrophobic) Can diffuse directly through the cell membrane Receptors are in the nucleus, cytoplasm, or on DNA They can activate or inhibit genes Transcribe and translate into proteins/enzymes Cells must have the appropriate receptors to receive the signals, otherwise they will induce an effect.

Examples of Steroid Hormones Androgens (testosterone) - masculinizing Estrogen - feminizing Progestins – pregnancy Cortisol – stress hormone

Peptide Hormones Include peptides, polypeptides, and glycoproteins They are water-soluble They must bind to receptors on the plasma membrane. Insulin is released by the pancreas in response to elevated blood glucose levels.

Peptide Hormones When they bind to membrane receptors, they change the shape of the receptor. This activates second messengers inside the cell.

Long-distance signaling Peptide Hormones Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell Types of membrane receptors: G-protein linked receptors Tyrosine kinases Ion channels

G-Protein-Linked Receptors Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate Segment that interacts with G proteins GDP GTP P i Signal-binding site When the signal binds, the receptor changes shape. It binds to the G-protein, causing GTP to replace GDP.

G-Protein-Linked Receptors Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate Segment that interacts with G proteins GDP GTP P i Signal-binding site The G-protein dissociates from the receptor and binds to the enzyme, triggering secondary messengers. The G-protein converts GTP back to GDP, becoming inactive.

Receptor Tyrosine Kinases Kinases – membrane receptors that are also enzymes. (They transfer phosphate groups to tyrosine amino acids) Signal molecule Signal-binding sitea CYTOPLASM Tyrosines Signal molecule Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP 6 ADP Abnormal RTK’s are associated with many different cancers.

Ligand-Gated Ion Channels Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Gate closed Ions Signals (ligands) open “gates” that allow ions to pass through. Gated Ion Channel

Second Messengers Cyclic AMP (cAMP) and Ca2+ are common second messengers (First messenger is the ligand) O –O N O P OH CH2 NH2 ATP Ch2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i 2nd Messenger

cAMP as Second Messenger ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine)

Relay molecules in a signal transduction pathway Peptide Hormones Signal transduction = cascade of messages allowing movement of an extracellular signal into the cell EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Reception 1 Transduction 2 Response 3

Phosphorylation cascade Signal Transduction Signal molecule Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P 

Cell B. Pathway branches, leading to two responses 2 3 Signal molecule Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response Activation or inhibition Receptor Relay molecules

Problems Associated with the Endocrine System Overproduction of hormones Underproduction of hormones Faulty receptors on target cells Androgen-Insensitivity Syndrome

Hypothalamus and Pituitary Gland Interact to produce and secrete hormones.

Hypothalamus and Pituitary Posterior pituitary releases ADH (antidiuretic hormone) and oxytocin

Hypothalamus and Pituitary Anterior pituitary receives hormones from the hypothalamus through capillaries.

Hypothalamus and Pituitary Anterior pituitary releases several “tropic” hormones. These hormones inhibit or stimulate other endocrine glands

Hypothalamus and Pituitary The four strictly tropic hormones are Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH)

Hypothalamus and Pituitary The “non-tropic” hormones include: Growth hormone (GH) Prolactin (PRL) Non-tropic hormones directly affect a non-endocrine target cell.

Thyroid Hormones The thyroid gland: Produces two iodine-containing hormones, triiodothyronine (T3) and thyroxine (T4)

The hypothalamus and anterior pituitary Control the secretion of thyroid hormones through two negative feedback loops Hypothalamus Anterior pituitary TSH Thyroid T3 T4 +

Roles of the Thyroid Hormones: Stimulating metabolism Influencing development and maturation

Hyperthyroidism An excessive secretion of thyroid hormones Can cause Graves’ disease in humans

Thyroid Gland Produces calcitonin

Parathyroid Glands Release parathyroid hormone (PTH)

The Pancreas Cells in the pancreas called “Pancreatic Islets” (Islets of Langerhans) regulate blood sugar levels Secrete two antagonistic hormones: Insulin Glucagon

Alpha cells of pancreas are stimulated to release Beta cells of pancreas are stimulated to release insulin into the blood. Insulin Liver takes up glucose and stores it as glycogen. Body cells take up more glucose. Blood glucose level declines to set point; stimulus for insulin release diminishes. STIMULUS: Rising blood glucose level (for instance, after eating a carbohydrate- rich meal) Homeostasis: (about 90 mg/100 mL) rises to set point; stimulus for glucagon Dropping blood glucose skipping a meal) Alpha cells of pancreas are stimulated to release glucagon into the blood. Liver breaks down glycogen and releases glucose into blood. Glucagon

Diabetes Mellitus Diabetes mellitus Is caused by a deficiency of insulin or a decreased response to insulin in target tissues Patients have elevated blood glucose levels

Type I diabetes mellitus (insulin-dependent diabetes) Is an autoimmune disorder in which the immune system destroys the beta cells of the pancreas Type II diabetes mellitus (non-insulin-dependent diabetes) Is characterized either by a deficiency of insulin or, more commonly, by reduced responsiveness of target cells due to some change in insulin receptors

Adrenal Glands: Response to Stress The adrenal glands include the adrenal medulla and the adrenal cortex.

Adrenal Medulla Secretes epinephrine (adrenaline) and norepinephrine (noradrenaline) Different receptors different cell responses Epinephrine a receptor b receptor Vessel constricts dilates Glycogen breaks down and glucose is released from cell (a) Intestinal blood vessel (b) Skeletal muscle blood vessel (c) Liver cell Different intracellular proteins Glycogen deposits

Adrenal Cortex Produces stress hormones: Glucocorticoids, such as cortisol Influence glucose metabolism and the immune system Mineralocorticoids, such as aldosterone Affect salt and water balance

Gonadal Sex Hormones The gonads = testes and ovaries Produce most of the body’s sex hormones: androgens, estrogens, and progestins

The Testes Synthesize androgens (testosterone) Stimulate the development and maintenance of the male reproductive system Increase muscle and bone mass

The Ovaries Produce estrogens (estradiol) Responsible for the maintenance of the female reproductive system and the development of female secondary sex characteristics Produce progestins (progesterone) Involved in preparing and maintaining the uterus

The Pineal Gland Secretes melatonin Release of melatonin is controlled by light/dark cycles The function of melatonin appears to be related to biological rhythms associated with reproduction

Endocrine System in Insects Hormones control insect molting and development. Brain Neurosecretory cells Corpus cardiacum Corpus allatum EARLY LARVA LATER LARVA PUPA ADULT Prothoracic gland Ecdysone Brain hormone (BH) Juvenile hormone (JH) Low JH Neurosecretory cells in the brain produce brain hormone (BH), which is stored in the corpora cardiaca (singular, corpus cardiacum) until release. 1 BH signals its main target organ, the prothoracic gland, to produce the hormone ecdysone. 2 Ecdysone secretion from the prothoracic gland is episodic, with each release stimulating a molt. 3 Juvenile hormone (JH), secreted by the corpora allata, determines the result of the molt. At relatively high concen- trations of JH, ecdysone-stimulated molting produces another larval stage. JH suppresses metamorphosis. But when levels of JH fall below a certain concentration, a pupa forms at the next ecdysone-induced molt. The adult insect emerges from the pupa. 4

Brain hormone Is produced by neurosecretory cells Stimulates the release of ecdysone from the prothoracic glands Brain Neurosecretory cells Corpus cardiacum Corpus allatum EARLY LARVA LATER LARVA PUPA ADULT Prothoracic gland Ecdysone Brain hormone (BH) Juvenile hormone (JH) Low JH Neurosecretory cells in the brain produce brain hormone (BH), which is stored in the corpora cardiaca (singular, corpus cardiacum) until release. 1 BH signals its main target organ, the prothoracic gland, to produce the hormone ecdysone. 2 Ecdysone secretion from the prothoracic gland is episodic, with each release stimulating a molt. 3 Juvenile hormone (JH), secreted by the corpora allata, determines the result of the molt. At relatively high concen- trations of JH, ecdysone-stimulated molting produces another larval stage. JH suppresses metamorphosis. But when levels of JH fall below a certain concentration, a pupa forms at the next ecdysone-induced molt. The adult insect emerges from the pupa. 4

Ecdysone Juvenile hormone Promotes molting and the development of adult characteristics Juvenile hormone Promotes the retention of larval characteristics Brain Neurosecretory cells Corpus cardiacum Corpus allatum EARLY LARVA LATER LARVA PUPA ADULT Prothoracic gland Ecdysone Brain hormone (BH) Juvenile hormone (JH) Low JH Neurosecretory cells in the brain produce brain hormone (BH), which is stored in the corpora cardiaca (singular, corpus cardiacum) until release. 1 BH signals its main target organ, the prothoracic gland, to produce the hormone ecdysone. 2 Ecdysone secretion from the prothoracic gland is episodic, with each release stimulating a molt. 3 Juvenile hormone (JH), secreted by the corpora allata, determines the result of the molt. At relatively high concen- trations of JH, ecdysone-stimulated molting produces another larval stage. JH suppresses metamorphosis. But when levels of JH fall below a certain concentration, a pupa forms at the next ecdysone-induced molt. The adult insect emerges from the pupa. 4