Endocrine System

Objectives

• Describe the major functions and organization, cellular and histological components, and homeostatic imbalances of the endocrine system.

• Explain the classification, mechanism, and secretion of hormones.

Introduction

• The endocrine system is like a postal system.

• It consists of ductless glands that synthesize and secrete hormones.

• Hormones are released into the bloodstream and transported throughout the body.

• Target cells have specific receptors for a hormone, allowing them to bind and respond.

Comparison: Nervous vs. Endocrine

• Similarities:

  • Both systems release ligands (chemical messengers).

  • Ligands bind to receptors on target cells.

• Endocrine System:

  • Hormones are transported via the blood.

  • Targets can be any cells with receptors, leading to widespread effects.

  • Longer reaction times compared to the nervous system.

  • Longer-lasting effects (minutes to days/weeks).

Local Hormones

• Local hormones do not circulate in the blood.

• Some biologists may not consider them true hormones.

• They bind to neighboring cells or the cells that release them.

• Eicosanoids are fatty acids within the phospholipid bilayer of the membrane.

Eicosanoid Effects

• Autocrine stimulation: effects on the same cell where the messenger was formed (like a post-it note).

• Paracrine stimulation: effects on neighboring cells (like interoffice mail).

General Functions of the Endocrine System

• Regulating development, growth, and metabolism.

• Maintaining homeostasis of blood composition and volume.

• Controlling digestive processes.

• Controlling reproductive activities.

Location of Major Endocrine Glands

• Endocrine organs have solely endocrine functions (e.g., pituitary, pineal, thyroid, parathyroid, and adrenal glands).

• Some "glands" are clusters of cells within organs with other functions (e.g., hypothalamus, skin, thymus, heart, liver, stomach, pancreas, small intestine, adipose connective tissue, kidneys, and gonads).

Synthesis and Release

• Reflex to stimulus:

  • Hormonal: in response to a hormone (e.g., TSH).

  • Humoral: in response to changes in levels of a nutrient or ion in the blood (e.g., Insulin).

  • Nervous: in response to neuron stimulation (e.g., Adrenal medulla, ADH).

Types of Endocrine Stimulation

• Hormonal stimulation: Release of a hormone in response to another hormone

• Humoral stimulation: Release of a hormone in response to changes in level of nutrient or ion in the blood

• Nervous system stimulation: Release of a hormone in response to stimulation by the nervous system

Hormonal Stimuli

• Negative feedback loop: Hypothalamic hormones à anterior pituitary à pituitary hormones à more hormones.

• Exception: Oxytocin à positive feedback loop.

Categories of Hormones

• Steroids:

  • Lipid-soluble molecules.

  • Derived from cholesterol.

  • Examples: Gonadal steroids, cortisol, calcitriol.

• Biogenic Amines:

  • Modified amino acids.

  • Examples: Catecholamines, thyroid hormone, melatonin.

  • Water-soluble, except for thyroid hormone, which is lipid-soluble.

• Proteins:

  • Most hormones fall into this category.

  • Water-soluble chains of amino acids.

  • Subgroups: small peptides, large polypeptides, glycoproteins.

  • Examples: Antidiuretic hormone, insulin, glucagon, growth hormone, erythropoietin.

Hormone Solubility

• Lipid-soluble (lipophilic):

  • Steroid/steroid-based/thyroid hormone.

• Water-soluble (hydrophilic):

  • Biogenic amine – protein based.

Transport in the Blood

• Lipid-soluble hormones require carrier molecules as they are not dissolved in plasma.

  • Carriers are water-soluble proteins.

  • Carriers protect the hormone.

  • Binding is temporary, with frequent attachment, detachment, and reattachment.

  • Bound hormone = 90%.

  • Unbound (free) hormone exits the blood for receptor binding.

• Water-soluble hormones are free in the blood.

  • A few use carrier proteins to prolong their life.

Levels of Circulating Hormone

• Determined by synthesis vs. elimination.

  • Hormone synthesis is controlled by glands.

  • Increased synthesis/release leads to increased blood concentration.

  • Decreased synthesis/release leads to decreased blood concentration.

• Hormone elimination:

  • Enzymatic degradation (liver).

  • Removal from blood (kidney).

  • Target cell uptake.

Half-Life

• Depends on elimination rate.

• Short half-life requires continuous maintenance of levels.

  • Water-soluble hormones generally have short half-lives.

  • Steroid hormones generally have long half-lives.

Lipid-Soluble Hormones and Intracellular Receptors

• Small, nonpolar, and lipophilic.

• Receptors are intracellular.

  • The unbound lipid-soluble hormone diffuses readily through the plasma membrane and binds with an intracellular receptor in the cytosol or nucleus, forming a hormone-receptor complex.

  • The hormone-receptor complex binds with a specific DNA sequence called a hormone-response element.

  • This binding stimulates mRNA synthesis.

  • mRNA exits the nucleus and is translated by a ribosome in the cytosol, resulting in the synthesis of a new protein.

Water-Soluble Hormones

• Polar, meaning receptors are on the cell surface.

• Utilize a signal transduction pathway.

  • Hormone = first messenger.

  • G-protein activation of a membrane enzyme (adenylate cyclase or phospholipase C).

  • Formation of a second messenger, which modifies cellular activity.

Activation of G Proteins

• Hormone (first messenger) binds to receptor and induces shape change to activate the receptor.

• G protein binds to activated receptor.

• GDP is "bumped off" and GTP binds to G protein; G protein is then activated.

• Activated G protein (with GTP) is released from the receptor and moves along the inside of the plasma membrane, which results in formation or availability of second messenger.

Action of G Proteins: Adenylate Cyclase Pathway

• Hormone binds receptor à G protein is activated à activates adenylate cyclase.

• Adenylate cyclase generates cAMP.

• cAMP activates protein kinase A.

• Protein kinase A phosphorylates other molecules (activating or inhibiting them).

Water-Soluble Hormones: Phospholipase C Pathway

• Hormone binds receptor à G protein is activated à activates phospholipase C.

  • Phospholipase C splits PIP2 into diacylglycerol (DAG) and inositol triphosphate (IP3).

  • DAG = second messenger of the membrane that activates protein kinase C, which phosphorylates other molecules.

Water-Soluble Hormones: Phospholipase C Pathway (continued)

• IP3 = second messenger.

  • Leaves membrane à increase in the levels of cytosolic Ca^{2+}.

  • Ca^{2+} acts as a third messenger, activating kinases (sometimes by binding to calmodulin) and interacting with ion channels.

Action of Water-Soluble Hormones

• Multiple results possible with different signal transduction pathways.

  • Enzymes can be activated or inhibited.

  • Growth can be stimulated (cell division).

  • Cellular secretions can be released.

  • Membrane permeability can be changed.

  • Muscles can be contracted or relaxed.

Amplification

• The hormone signals are amplified within the cell

Target Cells: Degree of Cellular Response

• Cell’s response to a hormone varies with:

  • Number of receptors.

  • Response to other hormones.

Number of Receptors

• Receptor number fluctuates.

  • Up-regulation: increases number of receptors, increasing sensitivity.

  • Down-regulation: decreases number of receptors, decreasing sensitivity.

Receptor/Hormone Interactions

• Different hormones can simultaneously bind to a cell.

  • Synergistic interactions: hormones work together to produce a greater effect (e.g., estrogen and progesterone).

  • Permissive interactions: first hormone allows action of second hormone (e.g., oxytocin and prolactin).

  • Antagonistic interactions: one hormone causes opposite effect of another hormone (e.g., glucagon and insulin).

Summary of Endocrine System

• What the endocrine system does.

• How the endocrine system does it – hormones.

• How hormones do what they do - solubility.

• Regulation:

  • Humoral

  • Neural

  • Hormonal

• Direct vs. indirect.

• Receptor availability/affinity.

• Elimination.

Hypothalamus and Pituitary

• The hypothalamus produces oxytocin and ADH

• The posterior pituitary stores and releases oxytocin and ADH

Major Endocrine Organs: Pituitary (Hypophysis)

• Pituitary gland – two lobes:

  • Neurohypophysis – posterior lobe (neural tissue).

    • Receives, stores, and releases hormones from the hypothalamus.

  • Adenohypophysis – anterior lobe (gland).

    • Synthesizes and secretes a number of hormones.

Pituitary-Hypothalamic Relationships: Posterior Lobe

• Posterior lobe = hypothalamic neural tissue, having a neural connection.

• Hypothalamus à oxytocin and ADH.

• Transported to the posterior pituitary.

Pituitary-Hypothalamic Relationships: Anterior Lobe

• Anterior lobe = out-pocketing of oral mucosa.

• No direct neural contact with the hypothalamus.

Hypothalamus and Anterior Pituitary Gland

• Hypothalamus hormonally stimulates anterior pituitary.

  • Hypothalamus secretes regulatory hormones.

  • Travel via portal blood vessels to pituitary (hypophyseal portal system).

• Anterior pituitary à hormones à circulation.

Hypothalamus and the Anterior Pituitary Gland

• Regulatory hormones of the hypothalamus:

  • Releasing hormones: increase secretion of anterior pituitary hormones.

  • Inhibiting hormones: decrease secretion of anterior pituitary hormones.

  • Oxytocin and ADH

Hypothalamus and the Anterior Pituitary Gland

• Anterior pituitary—tropic hormones and prolactin:

  • Thyroid stimulating hormone (TSH).

  • Prolactin (PRL).

  • Adrenocorticotropic hormone (ACTH; corticotropin).

  • Gonadotropins:

    • Follicle-stimulating hormone (FSH).

    • Leutenizing hormone (LH).

  • Growth hormone (GH; somatotropin).

Anterior Pituitary Hormones

• List and diagram showcasing hormones of the anterior pituitary, their targets, and regulating hormones from the hypothalamus

Growth Hormone

• Growth hormone (GH) functions include:

  • Stimulation of linear growth at epiphyseal plate.

  • Hypertrophy of muscle.

  • Release of nutrients from storage into blood.

• GHRH stimulates GH release.

• Release influenced by: age, time of day, and nutrient levels, stress and exercise.

Growth Hormone Release

• GH release changes with age

• GH release fluctuates based on the time of day (circadian rhythm).

Growth Hormone Release (continued)

• GH release changes in response to nutrient blood levels.

• GH release is altered by stress.

Growth Hormone

• GH and hepatocytes:

  • Hepatocytes release insulin-like growth factors (IGFs).

  • Increase glycogenolysis and gluconeogenesis.

• All body cells have receptors for GH, IGF, or both.

  • Cause increases in cell division, protein synthesis, cell differentiation.

  • Bone and muscle are particularly responsive.

Growth Hormone

• GH and IGFs cause adipose cells to release nutrients.

  • Cells increase lipolysis and decrease lipogenesis.

  • Increases levels of glycerol and fatty acids in blood.

  • Helps provide molecules necessary for generating ATP for growth.

• Negative feedback regulation of GHRH, GH release.

Regulation and Action of GH

• Diagram explaining the process and steps of GH release and regulation

Hypersecretion of GH

• What would be the consequence of hypersecretion of GH?

• What about hyposecretion?

Clinical Relevance: Gigantism

• Proctonation

Pituitary Dwarfism

• Results as a result of hyposecretion of GH

hypersecretion of GH after epiphyseal plates have fused

• What if… hypersecretion of GH after epiphyseal plates have fused?

Acromegaly

• Disorder associated with hypersecretion of GH after the epiphyseal plates have closed

Treatment Options

• Acromegaly

• Pituitary dwarfism

• Gigantism

The Relevant Example

• To use in clinical practice

Thyroid Gland and Thyroid Hormone

• Anatomy of the thyroid gland:

  • Inferior to thyroid cartilage of larynx, anterior to trachea.

  • Composed of microscopic follicles.

    • Follicular cells—Produce and release thyroid hormone (TH).

    • Follicle lumen houses colloid—a viscous, protein-rich fluid.

    • Parafollicular cells— make calcitonin.

The Thyroid Gland

• Visual representation of the anatomy of the thyroid gland

Thyroid Hormone Synthesis, Storage, and Release

• Explanation of the chemical equation required to synthesize, storage and release of the thyroid hormone

Thyroid Gland and Thyroid Hormone

• Action of thyroid hormone (TH)

  • Hypothalamic-pituitary-thyroid axis

    • Cold temperature, pregnancy, high altitude, hypoglycemia, or low TH cause hypothalamus to release TRH.

  • Follicular cells release two forms of TH to blood: T3 and T4

    • T3 = triiodothyronine; T4 = tetraiodothyronine

    • T3 and T4 are transported within blood by carrier molecules

Thyroid Gland and Thyroid Hormone

• Action of thyroid hormone (TH)

  • T3 versus T4

    • Thyroid gland produces more T4 but T3 is more active form

    • Most target cells convert T4 to T3

  • TH increases metabolic rate and protein synthesis in targets

    • Stimulates synthesis of sodium-potassium pumps in neurons

    • Calorigenic: generates heat, raises temperature

    • Stimulates increased amino acid and glucose uptake

    • Increases number of cellular respiration enzymes within mitochondria

Thyroid Gland and Thyroid Hormone

• Fosters energy (ATP) production

  • Hepatocytes à increase glycogenolysis and gluconeogenesis, and a decrease in glycogenesis

  • Adipose cells à increase in lipolysis and decrease in lipogenesis

  • glucose-sparing effect

• TH increases respiration rate

  • To meet additional oxygen demand

• TH increases heart rate and force of contraction

  • Causes heart to increase receptors for epinephrine and norepinephrine

Regulation and Action of TH

• Visual aid describing the process by which TH is regulated and its actions.

Clinical View: Disorders of Thyroid Hormone Secretion

• Hyperthyroidism

  • Graves’ disease

• Hypothyroidism

• Why do we look for high TSH?

Clinical View: Disorders of Thyroid Hormone Secretion

• Goiter

• Enlargement of the thyroid gland

Adrenal Glands and Cortisol

• Anatomy of the adrenal glands

  • Paired, pyramid-shaped endocrine glands

  • Perched on each kidney

  • Two regions

    • Adrenal medulla

    • Adrenal cortex

Adrenal Glands and Cortisol

• Anatomy of the adrenal glands

  • Adrenal medulla

    • Forms inner core of each adrenal gland

    • Releases epinephrine and norepinephrine with sympathetic stimulation

  • Adrenal cortex

    • Synthesizes more than 25 corticosteroids

    • Three regions producing different steroid hormones: zona glomerulosa, zona fasciculata, and the inner zona reticularis

Visual Representation

• Figure demonstrating the capsule, adrenal cortex and adrenal medulla.

Adrenal Glands and Cortisol

• Hormones of the adrenal cortex

  • Mineralocorticoids: hormones that regulate electrolyte levels

    • Zona glomerulosa

    • Aldosterone

  • Glucocorticoids: hormones that regulate blood sugar

    • Zona fasciculate

    • Cortisol increases blood sugar

  • Gonadocorticoids: sex hormones

    • Zona reticularis

    • Androgens

    • Converted to estrogen in females

    • Production < testes

Adrenal Glands and Cortisol

• Action of cortisol

  • Cortisol and corticosterone increase nutrient levels in blood

    • To resist stress and repair injured tissue

  • Release regulated by hypothalamic-pituitary-adrenal axis

    • Stress, late stages of sleep, and low levels of cortisol stimulate hypothalamus to release CRH

    • CRH stimulates anterior pituitary to release ACTH

    • ACTH stimulates adrenal cortex to release cortisol and corticosterone

Regulation and Action of Cortisol Hormone

• Visual depiction of the steps in the regulation/action of cortisol release.

Variables That Influence Levels of Cortisol

• Cortisol release fluctuates based on the time of day (circadian rhythm).

• Cortisol level is increased by stress.

Excessive Levels of Glucocorticoids

• Excessive levels of glucocorticoids:

  • Depress cartilage and bone formation

  • Inhibit inflammation

  • Depress the immune system

• How do we treat excessive inflammation in an athlete?

Clinical View: Disorders in Adrenal Cortex Hormone Secretion

• Cushing syndrome

  • Chronic exposure to excessive glucocorticoid hormones in people taking corticosteroids for therapy

  • Some cases when adrenal gland produces too much hormone

  • Obesity, hypertension, excess hair growth, kidney stones, and menstrual irregularities

• Addison disease

  • Characterized by insufficient hormones in the adrenal cortex.

Adrenal Medulla

• Specialized cells - epinephrine and norepinephrine

• Secretion of these hormones causes:

  • Blood glucose levels to rise

  • Blood vessels to constrict

  • The heart to beat faster

  • Blood to be diverted to the brain, heart, and skeletal muscle

Anatomy of the Pancreas

• Endocrine and exocrine functions

  • Acini cells à pancreatic juice

    • They make up vast majority of pancreas

  • Pancreatic islets (of Langerhans) contain clusters of endocrine cells

    • Alpha cells secrete glucagon

    • Beta cells secrete insulin

Pancreatic Anatomy

• Representation of the anatomical location of the abdominal organs in conjunction to the pancreas

Effects of Pancreatic Hormones

• Pancreatic hormones help maintain blood glucose

  • Normal range is 70 to 110 mg of glucose/deciliter

  • High levels damage blood vessels and kidneys

  • Low levels cause lethargy, mental and physical impairment, death

• Insulin lowers blood glucose

• Glucagon raises blood glucose

Regulation and Action of Insulin

• Visual diagram explaining the different steps of regulation and action of insulin

Regulation and Action of Glucagon

• Visual diagram explaining the different steps of regulation and action of glucagon

Clinical View

• Diabetes mellitus

  • Inadequate uptake of glucose from blood

  • Chronically elevated glucose, blood vessels damaged

  • Leading cause of retinal blindness, kidney failure, and non- traumatic amputations in the United States

  • Associated with increased heart disease and stroke

• Type 1 diabetes

  • Absent or diminished release of insulin by pancreas

  • Tends to occur in children and younger individuals

  • May have autoimmune component

  • Requires daily injections of insulin

Clinical View

• Type 2 diabetes

  • From decreased insulin release or insulin effectiveness

  • Obesity major cause in development

  • Tends to occur in older individuals, but can occur in young adults

  • Treatment with diet, exercise, and medications

• Gestational diabetes

  • Seen in some pregnant women

  • If untreated, causes risk to fetus and increases delivery complications

  • Increases chance of later developing type 2 diabetes

Clinical View

• Hypoglycemia

  • Glucose levels below 60 mg/DL

  • Numerous causes

    • Insulin overdose, prolonged exercise, alcohol use, liver or kidney dysfunction

    • Deficiency of glucocorticoids or growth hormone, genetics

  • Symptoms of hunger, dizziness, confusion, sweating, and sleepiness

  • Glucagon given if individual unconscious and unable to eat

Structures with an Endocrine Function

• Adipose tissue à leptin

• Kidneys

• Parathyroid glands

• Heart

• Pineal Gland

• Others…

Aging and the Endocrine System

• Endocrine changes with aging

  • Secretory activity wanes with age

  • Reduces efficiency of endocrine system functions

  • Decreased levels of normal hormones

    • E.g., decreased levels of GH and sex hormones

  • Reduced GH levels leading to loss of weight and body mass in elderly