Endocrine System Notes

Overview of the Endocrine System

• The endocrine system is composed of ductless glands that synthesize and secrete hormones.
• Hormones are released into the blood and transported throughout the body.
• Target cells have specific receptors for a hormone, allowing them to bind and respond.
• Hormone transport to target cells:
  • Hormones are released into the interstitial fluid and then enter the blood.
  • They are transported within the blood.
  • They randomly leave the blood and enter the interstitial fluid.
  • Finally, the hormone binds to the target cells’ receptors.

General Functions of the Endocrine System

• Regulating development, growth, and metabolism
  • Hormones help regulate embryonic cell division and differentiation.
  • Hormones regulate metabolism, including anabolism and catabolism.
• Maintaining homeostasis of blood composition and volume
  • Hormones regulate blood solute concentrations, such as glucose and ions.
  • Hormones regulate blood volume, cellular concentration, and platelet number.
• Controlling digestive processes
  • Hormones influence secretory processes and the movement of materials in the digestive tract.
• Controlling reproductive activities
  • Hormones affect the development and function of reproductive systems and the expression of sexual behaviors.

Types of Endocrine Stimulation

• Details regarding the types of endocrine stimulation would be provided here based on the content of slide 7, which is not available in the transcript.

Circulating Hormones

• Steroids
  • Lipid-soluble molecules synthesized from cholesterol.
  • Include gonadal steroids (e.g., estrogen) and steroids synthesized by the adrenal cortex (e.g., cortisol).
• Biogenic Amines (Monoamines)
  • Modified amino acids.
  • Include catecholamines, thyroid hormone, and melatonin.
  • Water-soluble except for thyroid hormone (TH).
  • TH is nonpolar, made from a pair of tyrosines, and lipid-soluble.
• Proteins
  • Most hormones fall into this category.
  • Water-soluble chains of amino acids.

Local Hormones

• Signaling molecules that don’t circulate in the blood.
• They bind to the cells that release them (autocrine stimulation) or neighboring cells (paracrine stimulation).
• Eicosanoids: A type of local hormone formed from fatty acids within the phospholipid bilayer of the membrane.
  • Synthesized through an enzymatic cascade.
  • Prostaglandins are eicosanoids.
    • Stimulate pain and inflammatory responses.
    • Aspirin and other nonsteroidal anti-inflammatory drugs block prostaglandin formation.

Transport in the Blood

• Most water-soluble hormones travel freely through the blood.
  • A few use carrier proteins to prolong their life.
• Lipid-soluble hormones require a carrier protein.
  • Lipid-soluble hormones do not dissolve readily in the blood.
  • Binding between the hormone and carrier is temporary.
  • Most of the hormone (90% or more) is bound to the carrier protein.
  • Only unbound (free) hormone is able to exit the blood and bind to target cell receptors.

Levels of Circulating Hormone

• A hormone’s blood concentration depends on how fast it is synthesized and eliminated.
• Hormone release and its concentration in the blood are positively correlated.
  • An increase in release results in a higher blood concentration, and vice versa.
• Hormone elimination occurs in multiple ways:
  • Enzymatic degradation in liver cells.
  • Removal from blood via kidney excretion or target cell uptake.
• The faster the elimination rate, the lower the blood concentration, and vice versa.

Levels of Circulating Hormone: Half-Life

• Half-Life: The time necessary to reduce a hormone’s concentration to half of its original level.
  • Depends on how efficiently it is eliminated.
• Hormones with a short half-life must be secreted frequently to maintain a normal concentration.
  • Water-soluble hormones generally have a short half-life.
    • For example, the half-life of small peptide hormones is a few minutes.
  • Steroid hormones generally have a long half-life.
    • Carrier proteins protect them.
    • For example, testosterone has a half-life of 12 days.

Lipid-Soluble Hormones

• Lipid-soluble hormones can diffuse across the target cell membrane.
  • Such hormones are small, nonpolar, and lipophilic.
  • Their receptors are in the cytosol or nucleus.
• Once the hormone enters the cell, it binds to a receptor, forming a hormone-receptor complex.
• The complex binds to a hormone-response element (HRE) of DNA.
• This results in the transcription of mRNA, which is translated into a protein.
• The protein may have structural or metabolic effects.

Water-Soluble Hormones

• Water-soluble hormones use membrane receptors.
  • Such hormones are polar and can’t diffuse through the membrane.
• Signal Transduction Pathway
  • The hormone is the first messenger, initiating events by binding to a receptor.
  • Binding activates a G-protein (an internal membrane protein that binds a guanine nucleotide).
  • G-protein activation causes activation of a membrane enzyme.
  • The activated enzyme catalyzes the formation of a second messenger—a chemical that modifies cellular activity.
• Adenylate Cyclase Activity
  • After a hormone (e.g., glucagon) binds to its receptor, the G protein is activated.
  • The activated G protein activates adenylate cyclase.
  • Adenylate cyclase generates cAMP.
  • cAMP activates a protein kinase (protein kinase A).
  • Protein kinase A phosphorylates other molecules (activating or inhibiting them).

Action of Water-Soluble Hormones

• Multiple results are possible with different signal transduction pathways:
  • Activation or inhibition of enzymatic pathways.
  • Growth through cellular division.
  • Release of cellular secretions.
  • Changes in membrane permeability.
  • Muscle contraction or relaxation.

Target Cells: Degree of Cellular Response

• A cell’s response to a hormone varies with:
  • Its number of receptors for the hormone.
  • Its simultaneous response to other hormones.

Number of Receptors on a Target Cell

• Receptor number fluctuates.
• Up-regulation: Increases the number of receptors.
  • Increases sensitivity to the hormone.
  • Sometimes occurs when blood levels of the hormone are low.
  • Sometimes occurs with changes in development, cell cycle, or cell activity.
• Down-regulation: Decreases the number of receptors.
  • Decreases sensitivity to the hormone.
  • Sometimes occurs when blood levels of the hormone are high.
  • Sometimes occurs with changes in development, cell cycle, or cell activity.

Hormone Interactions on a Target Cell

• Different hormones can simultaneously bind to a cell, and their effects may interact.
• Synergistic Interactions: One hormone reinforces the activity of another hormone.
  • For example, estrogen and progesterone effects on a target cell.
• Permissive Interactions: One hormone requires the activity of another hormone.
  • For example, oxytocin’s milk ejection effect requires prolactin’s milk-generating effect.
• Antagonistic Interactions: One hormone opposes the activity of another hormone.
  • For example, glucagon increases blood glucose, while insulin lowers it.

Anatomic Relationship of the Hypothalamus and the Pituitary Gland

• The hypothalamus controls the pituitary gland, which controls several other endocrine organs.
• Pituitary Gland (Hypophysis)
  • Lies inferior to the hypothalamus in the sella turcica of the sphenoid bone.
  • Pea-sized.
  • Connected to the hypothalamus by the infundibulum.
  • Partitioned into anterior and posterior pituitary.
• Posterior Pituitary (Neurohypophysis)
  • Smaller, neural part of the pituitary gland.
  • Hypothalamic neurons project through the infundibulum and release hormones in the posterior pituitary.
  • Somas in the supraoptic nucleus and paraventricular nucleus.
  • Axons in the hypothalamo-hypophyseal tract of the infundibulum.
  • Synaptic knobs within the posterior pituitary.
• Anterior Pituitary
  • The hypothalamo-hypophyseal portal system of blood vessels connects the hypothalamus to the anterior pituitary.
    • Primary plexus: Porous capillary network associated with the hypothalamus.
    • Secondary plexus: Capillary network associated with the anterior pituitary.
    • Hypophyseal portal veins: Drain the primary plexus and transport blood to the secondary plexus.

Interactions Between the Hypothalamus and the Posterior Pituitary Gland

• The posterior pituitary is the storage and release site for antidiuretic hormone (ADH) and oxytocin (OT).
• Hormones are made in the hypothalamus by neurosecretory cells.
  • Antidiuretic Hormone (Vasopressin)
    • Functions: Decrease urine production, stimulate thirst, and constrict blood vessels.
  • Oxytocin
    • Functions: Uterine contraction, milk ejection, and emotional bonding.

Interactions Between the Hypothalamus and the Anterior Pituitary Gland

• The hypothalamus hormonally stimulates the anterior pituitary to release its hormones.
• The hypothalamus secretes regulatory hormones.
  • Travel via portal blood vessels to the pituitary.
• The anterior pituitary secretes hormones into general circulation.
• Hormones of the Hypothalamus
  • Releasing Hormones:
    • Increase secretion of anterior pituitary hormones.
    • Include: thyrotropin-releasing hormone (TRH), prolactin-releasing hormone (PRH), gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and growth hormone-releasing hormone (GHRH).
  • Inhibiting Hormones:
    • Decrease secretion of anterior pituitary hormones.
    • Include: prolactin-inhibiting hormone (PIH) and growth-inhibiting hormone (GIH).
• Hormones of the Anterior Pituitary
  • Thyroid-Stimulating Hormone (TSH; Thyrotropin)
    • Release triggered by TRH from the hypothalamus.
    • Causes the release of thyroid hormone (TH) from the thyroid gland.
  • Prolactin (PRL)
    • Release triggered by PRH, inhibited by PIH from the hypothalamus.
    • Causes milk production and mammary gland growth in females.
  • Adrenocorticotropic Hormone (ACTH; Corticotropin)
    • Release triggered by CRH from the hypothalamus.
    • Causes the release of corticosteroids by the adrenal cortex.
  • Gonadotropins: Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
    • Release triggered by GnRH from the hypothalamus.
    • In females: regulate ovarian development and secretion of estrogen and progesterone.
    • In males: sperm development and secretion of testosterone.
  • Growth Hormone (GH; Somatotropin)
    • Causes the liver to secrete insulin-like growth factors 1 and 2 (IGF-1 and IGF-2).
    • GH and IGFs function synergistically to stimulate cell growth and division.

Growth Hormone: Its Regulation and Effects

• Regulation of Growth Hormone Release
  • Release is controlled through hormonal stimulation (GHRH and GHIH) from the hypothalamus.
    • GHRH: Growth hormone-releasing hormone.
    • GHIH: Growth hormone-inhibiting hormone.
  • The amount of GHRH released from the hypothalamus is impacted by:
    • A person’s age, time of day, nutrient levels, stress, and exercise.
• Effects of Growth Hormone
  • Stimulates the release of IGFs from the liver.
    • Similar functions as GH but longer half-life.
  • All cells have receptors for GH, IGFs, or both.
  • The hormone stimulates increased protein synthesis, cell division, and cell differentiation.
  • Also stimulates the release of nutrients from storage:
    • Glycogenolysis (breakdown of glycogen into glucose) is stimulated.
    • Gluconeogenesis (conversion of nutrients to glucose) is stimulated.
    • Glycogenesis (synthesis of glycogen) is inhibited.
    • Lipolysis (breakdown of triglycerides) is stimulated.
    • Lipogenesis (formation of triglycerides) is inhibited.

Anatomy of the Thyroid Gland

• Inferior to the thyroid cartilage of the larynx, anterior to the trachea.
• Left and right lobes connected at the midline by a narrow isthmus.
• Rich vascularization gives it a reddish color.
• Composed of microscopic follicles.
  • Follicular cells: Cuboidal epithelial cells that surround a central lumen; synthesize thyroglobulin (TGB).
    • Produce and release thyroid hormone (TH).
  • Follicle lumen houses colloid: a viscous, protein-rich fluid.
  • Parafollicular cells: Cells between follicles; make calcitonin.
    • Hormone that decreases blood calcium levels.

Thyroid Hormone: Synthesis, Storage, and Release

• Details regarding the synthesis, storage, and release of thyroid hormone would be provided here based on the content of slide 49, which is not available in the transcript.

Thyroid Hormone: Its Regulation and Effects

• Regulation of Thyroid Hormone Release
  • Hypothalamic-Pituitary-Thyroid Axis:
    • Cold temperature, pregnancy, high altitude, hypoglycemia, or low TH cause the hypothalamus to release TRH.
    • TRH causes the anterior pituitary to release TSH.
    • TSH binds to receptors of follicular cells, triggering the release of TH.
  • Follicular cells release two forms of TH to the blood: T3 and T4.
    • T3 = triiodothyronine; T4 = tetraiodothyronine.
    • T3 and T4 are transported within the blood by carrier molecules.
• Effects of Thyroid Hormone
  • Cellular transport brings TH into target cells, binds receptor.
  • T3 versus T4:
    • The thyroid gland produces more T4, but T3 is the more active form.
    • Most target cells convert T4 to T3.
  • TH increases metabolic rate and protein synthesis in targets.
    • Stimulates the synthesis of sodium-potassium pumps in neurons.
    • Calorigenic: generates heat, raises temperature.
    • Stimulates increased amino acid and glucose uptake.
    • Increases the number of cellular respiration enzymes within mitochondria.
  • Fosters energy (ATP) production.
  • Hepatocytes are stimulated to increase blood glucose:
    • TH causes increases in glycogenolysis and gluconeogenesis, and a decrease in glycogenesis.
  • Adipose cells are stimulated to increase blood glycerol and fatty acids:
    • TH causes an increase in lipolysis and a decrease in lipogenesis.
    • This saves glucose for the brain (glucose-sparing effect).
  • TH increases respiration rate to meet additional oxygen demand.
  • TH increases heart rate and force of contraction.
    • Increased blood flow to deliver more nutrients and oxygen.
    • Causes the heart to increase receptors for epinephrine and norepinephrine.

Clinical View: Disorders of Thyroid Hormone Secretion

• Hyperthyroidism
  • Results from excessive production of TH.
    • Increased metabolic rate, weight loss, hyperactivity, heat intolerance.
  • Caused by T_4 ingestion, excessive stimulation by the pituitary, or loss of feedback control in the thyroid (Graves' disease).
  • Treated by removing the thyroid (then giving hormone supplements).
• Hypothyroidism
  • Results from decreased production of TH.
    • Low metabolic rate, lethargy, cold intolerance, weight gain.
  • Caused by decreased iodine intake, loss of pituitary stimulation of the thyroid, post-surgical complications, or immune system destruction of the thyroid (Hashimoto thyroiditis).
  • Treated with thyroid hormone replacement.
• Goiter
  • Enlargement of the thyroid.
  • Typically due to insufficient dietary iodine.
    • Lack of dietary iodine prevents the thyroid from producing thyroid hormone.
    • Once relatively common in the United States, but no longer due to the addition of iodine to table salt.

Calcitonin: Its Regulation and Effects

• Calcitonin
  • Synthesized and released from parafollicular cells of the thyroid gland.
  • The stimulus for release is high blood calcium or stress from exercise.
  • Acts to decrease blood calcium levels by:
    • Inhibiting osteoclast activity.
    • Stimulating kidneys to increase excretion of calcium in urine.

Anatomy of the Adrenal Glands

• Located on the superior surface of each kidney.
• Retroperitoneal; embedded in fat and fascia.
• Two regions:
  • Adrenal Medulla
    • Forms the inner core of each adrenal gland.
    • Red-brown color due to extensive blood vessels.
    • Releases epinephrine and norepinephrine with sympathetic stimulation.
  • Adrenal Cortex
    • Synthesizes more than 25 corticosteroids.
    • Yellow color due to lipids within cells.
    • Three regions producing different steroid hormones: zona glomerulosa, zona fasciculata, and zona reticularis.

Anatomy of the Adrenal Glands: Hormones of the Adrenal Cortex

• Mineralocorticoids: Hormones that regulate electrolyte levels.
  • Made in the zona glomerulosa: thin, outer cortical layer.
    • Aldosterone fosters Na^+ retention and K^+ secretion.
• Glucocorticoids: Hormones that regulate blood sugar.
  • Made in the zona fasciculata: larger, middle cortical layer.
    • Cortisol increases blood sugar.
• Gonadocorticoids: Sex hormones.
  • Made in the zona reticularis: thin, inner cortical layer.
    • Androgens are male sex hormones made by the adrenals.
    • Converted to estrogen in females.
    • Amount produced by the adrenals is less than the amount from the testes.

Cortisol: Its Regulation and Effects

• Regulation of Cortisol Release
  • Cortisol and corticosterone increase nutrient levels in the blood to resist stress and repair injured tissue.
  • ACTH stimulates the adrenal cortex to release cortisol.
  • Cortisol levels are regulated by negative feedback.

Clinical View: Disorders in Adrenal Cortex Hormone Secretion

• Cushing Syndrome
  • Chronic exposure to excessive glucocorticoid hormones in people taking corticosteroids for therapy.
  • In some cases, when the adrenal gland produces too much hormone.
  • Symptoms: Obesity, hypertension, hirsutism (excess male-pattern hair growth), kidney stones, and menstrual irregularities.
• Addison Disease
  • Form of adrenal insufficiency.
  • Develops when adrenal glands fail to produce enough hormones.
  • Chronic shortage of glucocorticoids and sometimes mineralocorticoids.
  • May develop from a lack of ACTH or a lack of response to ACTH.
  • Symptoms: Weight loss, fatigue and weakness, hypotension, and skin darkening.
  • Therapy includes oral corticosteroids.

Clinical View: Stress Response

• Stressors elicit a stress response.
• The hypothalamus initiates a neuroendocrine response.
• Three stages:
  • Alarm Reaction
    • The initial response involves sympathetic nervous system activation, epinephrine, and norepinephrine.
  • Stage of Resistance
    • After depletion of glycogen stores, the adrenal secretes cortisol to raise blood sugar and help meet energy demands.
  • Stage of Exhaustion
    • After weeks or months, depletion of fat stores results in protein breakdown for energy, leading to weakening of the body and illness.

Anatomy of the Pancreas

• Located posterior to the stomach, between the duodenum and the spleen.
• The pancreas has endocrine and exocrine functions.
  • Acinar cells generate exocrine secretions for digestion.
  • Pancreatic islets (of Langerhans) contain clusters of endocrine cells:
    • Alpha cells secrete glucagon.
    • Beta cells secrete insulin.

Pancreatic Hormones

• Pancreatic hormones help maintain blood glucose.
  • The 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, and death.
• Lowering High Blood Glucose Levels with Insulin
  • After food intake, beta cells detect a rise in blood glucose and respond by secreting insulin.
  • Insulin travels through the blood and randomly leaves the bloodstream to encounter target cells.
  • Insulin binds to receptors and initiates 2nd messenger systems.
  • Once blood glucose falls, beta cells stop secreting insulin.
  • Hepatocytes remove glucose from blood and store it as glycogen.
  • Adipose cells decrease fatty acid levels in blood and store fat.
  • Most body cells increase nutrient uptake in response to insulin.
  • Some cells do not require insulin to take in glucose, including neurons, kidney cells, hepatocytes, and red blood cells.

Clinical View: Conditions Resulting in Abnormal Glucose Levels

• Inadequate uptake of glucose from the blood results in chronically elevated glucose levels, which damage blood vessels.
  • Leading cause of retinal blindness, kidney failure, and non-traumatic amputations in the United States.
  • Associated with increased heart disease and stroke.
• Diabetes Mellitus
  • Type 1 Diabetes:
    • Absent or diminished release of insulin by the pancreas.
    • Tends to occur in children and younger individuals.
    • May have an autoimmune component.
    • Requires daily injections of insulin.
  • Type 2 Diabetes:
    • From decreased insulin release or insulin effectiveness.
    • Obesity is a major cause in development.
    • Tends to occur in older individuals but can occur in young adults.
    • Treatment with diet, exercise, and medication.
  • Gestational Diabetes:
    • Seen in some pregnant women.
    • If untreated, causes risks to the fetus and increases delivery complications.
    • Increases the chance of later developing type 2 diabetes.
• 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 is given if the individual is unconscious and unable to eat.

Pancreatic Hormones: Raising Low Blood Glucose Levels with Glucagon

• Alpha cells detect a drop in blood glucose and release glucagon.
• Glucagon acts through membrane receptors and 2nd messengers, causing body cells to release stored nutrients into the blood.
  • Hepatocytes release glucose:
    • Glycogenolysis and gluconeogenesis are stimulated; glycogenesis is inhibited.
  • Adipose cells release fatty acids and glycerol:
    • Lipolysis is stimulated, while lipogenesis is inhibited.
• Glucagon does not affect protein composition.
• Glucagon can be given by paramedics to unconscious individuals with low blood sugar.
• Once blood glucose rises, glucagon release is inhibited.

Pineal Gland

• The pineal gland is a small, unpaired body in the epithalamus of the diencephalon.
• The pineal gland secretes melatonin at night, which causes drowsiness, regulates circadian rhythm, and has effects on mood.
• Melatonin influences GnRH secretion.

Parathyroid Glands

• There are between 2 and 6 parathyroid glands (usually 4).
  • Located on the posterior surface of the thyroid gland.
  • Contain chief cells and oxyphil cells.
  • Chief (principal) cells make parathyroid hormone (PTH).
    • PTH increases blood calcium, liberates it from bone, decreases its loss in urine, and activates calcitriol hormone.

Structures with an Endocrine Function: Adipose Connective Tissue

• Adipose connective tissue secretes leptin.
  • Leptin controls appetite by binding to neurons in the hypothalamus.
  • Lower body fat is associated with less leptin, which stimulates appetite.
• Excess adipose raises the risk of cancer.
• Excess adipose delays male puberty.
• Abnormally low adipose interferes with the female menstrual cycle.
• Adipose has other endocrine effects.