Chemical Signals and Hormones

Chemical Signaling

• Physiological regulatory systems in multicellular animals require cell-to-cell communication.
• Chemical signals facilitate this communication.
• There are different classes of chemical signals

Chemical Signal Classes

• Growth factors mediate cell division.
• Morphogens mediate developmental processes.
• Cytokines control immune system cells.
• Neurotransmitters enable nerve cell communication.
• Endocrines secreted by epithelial cells into extracellular fluid and circulating in the blood are hormones.

Hormones Defined

• Hormones are secreted chemicals formed in specialized cells
• Hormones affect target cell function after traveling through body fluids.
• Hormones coordinate and control body functions.

Endocrine vs Nervous System

• The endocrine system uses hormones
• The endocrine system results in slow-acting and long-lasting (usually) effects
• The endocrine system coordinates growth and development, digestion, metabolism, and reproduction.
• The nervous system is fast-acting, short-lasting, and uses specific targeting.
• Nervous signals can affect nerve, muscle, and endocrine cells
• The nervous system is suited for rapid response to environmental stimuli
• Hormones are released into extra-cellular fluid.
• The primary hormone function is hormone production and secretion, scattered to target cells via blood (or hemolymph) throughout the body
• Hormones influence homeostasis, responses to environmental stimuli, and regulation of growth and development.
• Hormones are also involved in maintenance of constant body temperature (in endothermic animals), coordination of body's responses to stress, regulation/control of blood sugar, maintenance of water balance and reproduction.

Endocrine System Details

• Chemical signaling by hormones occurs within the endocrine system.
• Hormones are produced by cells in nearly all of the body's organs, often in specialized ductless glands (endocrine glands).
• Examples of endocrine glands include the hypothalamus, pineal, pituitary, thyroid, parathyroid, thymus, adrenal, ovary, and testis.

Paracrine and Autocrine Signaling

• Cells produce and secrete local regulators that reach nearby target cells, (paracrine), or act on the secreting cells themselves, (autocrine) by diffusion.
• This signaling is important in blood pressure regulation, nervous system function and reproduction.
• Prostaglandins (modified fatty acids) are involved in local signaling, their section is secreted in response to injury, promoting inflammation and pain sensation.
• Anti-inflammatory drugs (aspirin and ibuprofen) block prostaglandin synthesis.
• Neurohormones are secreted by nerve cells
• Pheromones are released by one animal to affect the behavior/physiology of another animal.

Chemical Classes of Hormones

• Protein/polypeptide hormones are the most abundant class, generally water-soluble; insulin and glucagon are examples
• Steroid hormones are lipid-soluble, containing four fused carbon rings; all synthesized from cholesterol.
• Steroid hormones are usually bound to large, soluble molecule carriers in blood; e.g., aldosterol and cortisol (made in adrenal glands), progesterone, estrogen, and testosterone
• Amine hormones can synthesize tryptop, epinephrin, or dopami

Cellular Response Pathways

• Water versus lipid solubility dictates the cellular response pathway.
• Water-soluble hormones generally cannot cross cell membranes
• Water-soluble hormones bind to receptors displayed on target cell surfaces
• Binding is covalent and reversible.
• The hormone binding triggers a cellular response, such as activation of an enzyme, change in uptake/secretion of specific molecules, or change in cytoskeleton.
• These responses are a series of changes in cellular proteins that converts the signal to an intracellular transduction pathway.
• Lipid-soluble hormones are not soluble in blood - require a transport protein
• Lipid-soluble hormones may enter the cell nucleus to trigger transcription (RNA synthesis) of certain genes.
• This proceeds by an intracellular receptor – hormone-receptor complex that moves into nucleus.

Examples of Hormone Classes

• Epinephrine is a water-soluble hormone

• It binds to a membrane-bound receptor.

• This causes a cytoplasmic response mediated by a second messenger.

• Epinephrine does not trigger a change in gene expression in this particular example

• Estradiol is a lipid-soluble hormone

• Its cytoplasmic receptor forms a hormone-receptor complex that enters the nucleus. -There, binds to DNA-binding protein or response element and changes gene expression (mRNA production)

Fight or Flight Response

• The brain detects danger and signals adrenal glands to release epinephrine, norepinephrine, and cortisol to the blood, prompting several physiological responses.
• Pupils dilate to allow more light in
• Muscles change the shape of the lens, decreasing short-range vision, decreasing peripheral vision.
• The liver breaks down glycogen to supply glucose (fuel) to the blood.
• Smooth muscle in the walls of stomach blood vessels constricts, shunting more blood to muscles
• The heart beats faster and stronger.
• Blood pressure rises.
• Fat cells release fatty acids (fuel) to the blood.
• Smooth muscle in walls of blood vessels in skeletal muscle dilate

Epinephrine Effects

• Epinephrine has multiple effects including metabolic and circulatory
• in liver cells, epinephrine binds to B receptors and glycogen breaks down until glucose is released from the cell
• In smooth muscle cells in wall of blood vessel that supplies skeletal muscle, epinephrine binds to B receptors to cause cell relaxation
• In smooth muscle cell in wall of blood vessel that supplies intestines, epinephrine binds to alpha receptors to cause cell contraction

Thyroid Regulation

• It plays a part in thermoregulation, bioenergetics, blood pressure, heart rate, muscle tone
• TRH (Thyrotropin Releasing Hormone) has endocrine gland/cells as target
• TRH stimulates production/secretion of TSH (Thyroid Stimulating Hormone) in the anterior pituitary
• TSH stimulates production/secretion of T3 and T₄ (Thyroid Hormone) in the thyroid gland
• T3 and T₄ stimulate cellular metabolism
• They maintain normal blood pressure, heart rate, and muscle tone
• They regulate digestive and reproductive functions.
• Diminished thyroid function is labeled as Hypothyroidism, and the symptoms include weight gain, lethargy, and intolerance to cold in adults.
• Iodine deficiency affects the levels of T3 and T4, which causes the normal negative feedback on TRH and TSH to not occur, This causes enlargement of the thyroid gland (visible goiters).
• 30% of the world population is susceptible to iodine deficiency.
• Excessive secretion of thyroid hormone is labelled as Hyperthyroidism, and it causes symptoms including high body temperature, profuse sweating, weight loss, high blood pressure.
• Autoimmune disorder in which antibodies bind to and activate TSH receptors,sustaining thyroid hormone production; affects 0.2-1.4% of the global population.
• Treatments for Hypothyroidism involve radioactive iodine therapy, drugs, and surgical removal of thyroid

Blood Glucose Control

• Homeostatic control maintains a set point of 70-110 mg/100 mL blood glucose level.
• Two antagonistic hormones, insulin and glucagon, regulate blood glucose levels
• Insulin decreases circulating glucose levels
• Glucagon increases circulating glucose levels

Diabetes Introduction

• Glucagon and insulin are made in the pancreas in clusters of cells called pancreatic islets or islets of Langerhans.
• These two types of cells make up only 1-2% of pancreatic mass
• Alpha cells produce and secrete glucagon.
• Beta cells produce and secrete insulin.

Type I Diabetes

• Insulin-dependent diabetes accounts for <10% of diabetes cases.
• It is an autoimmune disorder where the beta cells of the pancreas are destroyed and usually appears during childhood.
• Chronically high blood glucose levels are an effect.
• It is treatable with insulin injections, now obtainable through genetically engineered bacteria.
• Stem cell research may hold a possible cure if beta cells can be restored.

Type II Diabetes

• Non-insulin-dependent diabetes is typical in adult-onset
• In Type II Diabetes, the pancreas does not produce enough insulin, and skeletal muscle and adipose tissue cells respond poorly to insulin and take up less glucose than normal
• Blood glucose levels remain elevated but can be controlled through diet, exercise, and medications
• 38 million US adults have diabetes, and 20 % don't know that they have it.
• Medical costs and lost work and wages for people with diagnosed diabetes total $413 billion yearly
• Banting, Best, and Collip were awarded U.S. patents on insulin and the method used to make it. They sold these patents to the University of Toronto for $1 each.
• Eli Lilly began manufacturing insulin on a mass scale on 15 October 1923

Insulin Costs

• As of January 1st, 2023 for Medicare Part D, the insulin price is capped at $35/month
• As of July 1st, 2023, for Medicare Part B, the insulin price is capped at $35dollars/mo
• Representative statements stated that it is intended that the Affordable Insulin Now Act extend this $35/month cap to all Americans
• West Virginia and Mississippi had the highest diagnosed diabetes rates of any state.