Endocrine System Notes

Endocrine System

The endocrine system is composed of organs that produce hormones, engaging with all other systems in the body, and releasing these hormones into the blood.

Endocrine System Overview

The endocrine system works with the nervous system to coordinate and integrate the activity of cells throughout the body. It influences cellular activities through hormones transported in the blood. Endocrine system responses are slower but longer-lasting than those of the nervous system.

Endocrinology

Endocrinology is the study of hormones and endocrine organs.

Endocrine System Controls and Integrates

The endocrine system maintains homeostasis, regulates reproduction, growth, and development, and maintains electrolyte, water, and nutrient balance in the blood. It also regulates cellular metabolism and energy balance and mobilizes body defenses.

Exocrine vs. Endocrine Glands

Exocrine glands produce nonhormonal substances like sweat and saliva and have ducts to carry secretions to membrane surfaces. Endocrine glands secrete hormones into the blood, producing hormones and lacking ducts.

Glands

The endocrine glands include the pituitary, thyroid, parathyroid, adrenal, and pineal glands. The hypothalamus is a neuroendocrine organ.

Other hormone-producing tissues and organs include adipose cells, the thymus, and cells in the walls of the small intestine, stomach, kidneys, and heart.

Chemical Messengers of the Endocrine System

The chemical messengers of the endocrine system involve autocrines and paracrines. These are local chemical messengers transported via the blood but not considered part of the endocrine system.

Pathways of Signaling

• Paracrine signaling: Signaling to nearby cells.

• Autocrine signaling: Signaling to the same cell.

• Endocrine signaling: Hormones circulate systemically, affecting only cells with receptors for that hormone.

Target Cells

Target cells are tissues with receptors for a specific hormone, which alters target cell activity. Hormone action on target cells may:

• Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels.

• Stimulate the synthesis of enzymes or other proteins.

• Activate or deactivate enzymes.

• Induce secretory activity.

• Stimulate mitosis.

Hormone Release

Hormone release is controlled by neural, humoral, and hormonal stimuli.

• Humoral Stimuli: In response to changing levels of ions or nutrients in ECF (e.g., blood glucose triggers insulin release).

• Neural Stimuli: The nervous system signals endocrine glands to release hormones in response to stimuli (e.g., sympathetic fibers stimulate the adrenal medulla to secrete epinephrine and norepinephrine).

• Hormonal Stimuli: Tropic hormones stimulate other endocrine organs to release their hormones.

Blood levels of hormones are controlled by negative feedback systems. Endocrine glands make less hormone when levels are high and more when levels are low, maintaining homeostasis.

Nervous System Modulation

The nervous system can adjust hormone levels when needed, modifying the stimulation or inhibition of endocrine glands. It can override normal endocrine controls (e.g., under severe stress, the hypothalamus and sympathetic nervous system override insulin to increase blood glucose for fight or flight).

Classes of Hormones

• Amino acid-based hormones

  • Water-soluble and lipid-insoluble

  • Act on plasma membrane receptors via signal transduction

  • The hormone itself does not enter the cell

• Steroids

  • Synthesized from cholesterol

  • Lipid-soluble and water-insoluble

  • Can go through the cell membrane and bind to receptors inside the cell in the nucleus

Target Cell Specificity

Target cells must have specific receptors to which a hormone binds. Target cell activation depends on:

1. Blood levels of the hormone

2. Relative number of receptors on the target cell

3. Affinity of binding between the receptor and hormone

Up-regulation and Down-regulation

• Up-regulation: Target cells form more receptors in response to low hormone levels.

• Down-regulation: Target cells lose receptors in response to high hormone levels, maintaining homeostasis.

Half-Life, Onset, and Duration of Hormone Activity

These factors depend on whether the hormone is water-soluble or lipid-soluble.

Water-soluble hormones circulate freely, while lipid-soluble hormones are bound to plasma proteins.

Concentration of Circulating Hormone

The concentration reflects the rate of release and the speed at which it is inactivated and removed from the body.

Hormone Removal

Hormones are removed from the blood by:

• Degradation by enzymes in blood or cells

• Metabolism by the liver

• Removal via the kidneys

Response Times

• Water-soluble hormones: Fast response time (short duration)

• Lipid-soluble hormones: Longer response time (long duration)

Some responses are immediate, while others can take hours to days. Some hormones are inactive until they enter target cells.

Duration

The duration of hormone activity ranges from 10 seconds to several hours. The shorter the half-life, the more quickly the hormone is removed from the blood.

Interaction of Hormones at Target Cells

Hormones act on target cells through:

• Synergism: More than one hormone produces the same effects, causing amplification (e.g., cortisol and glucagon).

• Antagonism: One or more hormones oppose the action of another hormone (e.g., insulin and glucagon).

• Permissiveness: One hormone cannot exert its effects without another hormone being present (e.g., reproductive hormones need thyroid hormone).

The Hypothalamus and Pituitary Gland

The hypothalamus coordinates the autonomic nervous system (ANS) and the endocrine system and is a major regulating structure of the endocrine system.

It is connected to the pituitary gland via the infundibulum.

Pituitary Gland (Hypophysis)

The pituitary gland secretes nine hormones and has two major lobes:

• Neurohypophysis (Posterior Pituitary)

  • Composed of neural tissue that secretes neurohormones

  • Maintains a neural connection to the hypothalamus via the hypothalamo-hypophyseal tract

  • Secretes oxytocin and antidiuretic hormone (ADH), which are stored in axon terminals and released into the blood when neurons fire.

• Adenohypophysis (Anterior Pituitary)

  • Consists of glandular tissue and is vascularly connected to the hypothalamus via the hypophyseal portal system.

  • The hypothalamus secretes releasing and inhibiting hormones to regulate hormone secretion.

Hypothalamic Control

• Adenohypophysis: Hypothalamic hormones released into blood vessels control the release of anterior pituitary gland hormones.

• Neurohypophysis: Hypothalamic neurons synthesize oxytocin and ADH, which are sent down axons to axon terminals in the posterior pituitary for storage and release.

Neurohypophysis and Hypothalamic Hormones

• Oxytocin: "Social bonding" hormone, stimulates uterine contractions during childbirth and milk ejection, important for bonding.

• Antidiuretic Hormone (ADH): Targets kidney tubules to reabsorb more water and inhibit urine formation.

Diseases

• Diabetes Insipidus: ADH deficiency due to damage to the hypothalamus or neurohypophysis, leading to increased urine output. Need to stay well hydrated.

Adenohypophysis Hormones

All are peptide hormones and include:

• Growth Hormone (GH): Promotes metabolism and growth (bone and muscle).

  • Hypersecretion: Gigantism in children, acromegaly in adults.

  • Hyposecretion: Pituitary dwarfism in children.

• Thyroid-Stimulating Hormone (TSH): Stimulates normal development and secretory activity of the thyroid.

• Adrenocorticotropic Hormone (ACTH): Stimulates the adrenal cortex to release corticosteroids (cortisol).

• Gonadotropins: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

• Prolactin (PRL): Stimulates milk production in females.

Gonadotropins

• Follicle-Stimulating Hormone (FSH): Stimulates the production of gametes.

• Luteinizing Hormone (LH): Promotes the production of gonadal hormones.

  • Females: LH helps mature follicles, triggers ovulation, and causes the release of estrogen and progesterone.

  • Males: LH stimulates the production of testosterone.

• Prolactin (PRL): Stimulates milk production in females; its release is stimulated by suckling and estrogen.

Thyroid Gland Location and Structure

• Follicles: Hollow spheres of epithelial follicular cells that are the site of thyroid hormone synthesis.

• Colloid: Fluid of follicle lumen containing thyroglobulin and iodine, a precursor to thyroid hormone.

• Parafollicular cells: Produce calcitonin.

Thyroid Hormone (TH)

The body’s major metabolic hormone, affecting every cell by binding to intracellular receptors and triggering transcription of metabolic genes. It regulates:

• Basal metabolic rate and heat production

• Tissue growth and development

Thyroid Hormone Synthesis

The thyroid gland stores hormone in the follicle lumen until triggered by TSH to release it.

1. Thyroglobulin Synthesis: Thyroglobulin is synthesized and discharged into the follicle lumen.

2. Iodide Trapping: Iodide ions are actively taken into cells and released into the lumen.

3. Iodide Oxidation: Electrons are removed, converting iodide to iodine.

4. Iodine Attachment to Tyrosine: Catalyzed by peroxidase enzymes, forms monoiodotyrosine (MIT) and diiodotyrosine (DIT).

5. Iodinated Tyrosine Molecules Link Together: Forms T3 (DIT + MIT) and T4 (2 DITs).

6. Colloid Endocytosis: Colloid is endocytosed by follicular cells.

7. Lysosomal Enzymes: Lysosomal enzymes cleave T3 and T4 from thyroglobulin, and the hormones are secreted into the bloodstream.

• Most T4 is secreted, then transformed to T3 in the cell.

• Thyroid hormone has a globulin protein that helps it move via blood even though it's an AA hormone.

T3 and T4 both bind to target receptors, but T3 is more active. Peripheral tissues have an enzyme needed to convert T4 to T_3.

Regulation of TH Release

TH release is regulated by a negative feedback loop.

• ↓ TH levels stimulate TSH release.

• ↑ TH levels provide negative feedback inhibition on TSH release.

Diseases Related to TH

• Hyposecretion of TH:

  • In adults: myxedema (↓ metabolic rate, thick/dry skin, puffy eyes, cold, constipation, edema, cloudiness, lethargy).

  • Lack of Iodine: Goiter (↓ TH levels, triggers ↑ TSH secretion, thyroid synthesizes more unusable thyroglobulin, thyroid enlarges).

• Hypersecretion of TH: Graves' disease (autoimmune disease, body makes abnormal antibodies directed against thyroid follicular cells).

Calcitonin

Calcitonin is produced by parafollicular cells in response to high Ca^{2+} levels.

• Antagonist to parathyroid hormone (PTH).

• Inhibits osteoclast activity, prevents release of Ca^{2+} from bone matrix, and stimulates Ca^{2+} uptake into bone.

Parathyroid Gland

Four to eight tiny yellow-brown glands embedded in the posterior thyroid secrete parathyroid hormone (PTH).

PTH is important in Ca^{2+} homeostasis, secreted in response to low blood Ca^{2+} and inhibited by high levels of Ca^{2+}.

• Target: Skeleton, kidneys, and intestines.

• Functions: It stimulates osteoclasts to digest bone and release Ca^{2+} to blood, enhances reabsorption of Ca^{2+} and secretion of phosphate by kidneys, and promotes activation of vitamin D by kidneys.

Adrenal Gland

Paired, pyramid-shaped organs atop the kidneys consisting of the adrenal cortex and adrenal medulla.

Adrenal Cortex

It has three layers of glandular tissue that synthesize and secrete corticosteroids, steroid hormones that are not stored in cells; their rate of release depends on the rate of synthesis.

• Zona glomerulosa: Mineralocorticoids (e.g., aldosterone).

• Zona fasciculata: Glucocorticoids (e.g., cortisol).

• Zona reticularis: Gonadocorticoids (e.g., androgens).

Mineralocorticoids

They regulate electrolyte concentrations (Na+, K+) in ECF, affecting ECF volume, blood pressure, and levels of other ions.

Aldosterone: Most potent mineralocorticoid stimulates Na^+ reabsorption by the kidneys, causing water retention and increasing blood volume and BP. It also stimulates K^+ elimination by the kidneys.

Glucocorticoids

Influence metabolism of most cells and help resist stressors. Maintain blood glucose levels by increasing blood sugar, fatty acids, and amino acids. Maintain BP by increasing action of vasoconstrictors.

Cortisol (hydrocortisone): The only significant glucocorticoid in humans, elevated during everyday stressors.

Regulation of secretion:

1. Hypothalamus releases corticotropin-releasing hormone (CRH).

2. CRH stimulates the adenohypophysis to release ACTH.

3. ACTH stimulates the adrenal cortex to release cortisol.

4. Cortisol inhibits ACTH and CRH release via negative feedback.

Cortisol secretion is also regulated by eating and activity patterns, and acute stress can override cyclical cortisol rhythm.

Actions of Cortisol

• Increases blood levels of glucose, fatty acids, and amino acids.

• Gluconeogenesis: Formation of glucose from fats and proteins.

• Enhances vasoconstriction and increases BP to quickly distribute nutrients to cells.

Homeostatic Imbalances of Glucocorticoids

Excessive levels of glucocorticoids (cortisol) can depress cartilage and bone formation, inhibit inflammation, depress the immune system, and disrupt normal cardiovascular, neural, and gastrointestinal functions.

• Hypersecretion: Cushing's syndrome (tumor on pituitary, lungs, pancreas, kidney, or adrenal cortex; overuse of corticosteroids).

• Hyposecretion: Addison's disease (deficit in glucocorticoids and mineralocorticoids).

Addison's Disease Symptoms and Treatment

Symptoms include decreased plasma glucose and Na^+ levels, weight loss, severe dehydration, and low BP. Early signs: bronzing of skin.

Treatment: corticosteroid replacement therapy.

Gonadocorticoids

Weak androgens (e.g., androstenedione, dehydroepiandrosterone [DHEA]) converted to testosterone in tissue cells or estrogens. They contribute to the onset of puberty, appearance of secondary sex characteristics, sex drive in women, and source of estrogen in postmenopausal women.

Adrenal Medulla

Nervous tissue, part of the sympathetic nervous system. Medullary chromaffin cells synthesize catecholamines (epinephrine [80%] and norepinephrine [20%]).

• Effects: Fight/flight response, vasoconstriction, increased heart rate, increased blood glucose levels, and blood diverted to the brain, heart, and skeletal muscles.

The response to stressors is brief, unlike adrenal cortical hormones.

Pineal Gland

Small gland hanging from the roof of the third ventricle that secretes melatonin, derived from serotonin.

Melatonin may affect the timing of sexual maturation and puberty, day/night cycles, and physiological processes that show rhythmic variations (body temperature, sleep, appetite). It also affects the production of antioxidant and detoxification molecules in cells.

Blue light inhibits melatonin secretion.

Pancreas

A gland located partially behind the stomach, embedded in the abdominal mesentery, having both exocrine and endocrine cells.

• Acinar cells (exocrine): Produce enzyme-rich juice for digestion via a duct into the duodenum.

• Pancreatic islets (endocrine): Contain cells that produce pancreatic hormones (alpha and beta cells).

• Alpha (α) cells: Produce glucagon (hyperglycemic hormone).

• Beta (β) cells: Produce insulin (hypoglycemic hormone).

Glucagon

Glucagon is triggered by decreased blood glucose levels, rising amino acid levels, or sympathetic nervous system activation, releasing glucose into the blood (↑ glucose[]).

• Raises blood glucose levels by targeting the liver to break down glycogen into glucose (glycogenolysis) and synthesize glucose from lactic acid and other noncarbohydrates (gluconeogenesis).

Insulin

Secreted when blood glucose levels increase, primarily from digestion, lowering blood glucose levels in three ways:

1. Enhances membrane transport of glucose into fat and muscle cells.

2. Inhibits the breakdown of glycogen to glucose.

3. Inhibits the conversion of amino acids or fats to glucose.

Diabetes Mellitus

• Hypossecretion of insulin (Type 1).

• Hypoactivity of insulin (Type 2).

3 Cardinal Signs of DM

1. Polyuria: Huge urine output.

2. Polydipsia: Excessive thirst.

3. Polyphagia: Excessive hunger and food consumption.

Gonads and Placenta

Regulated by gonadotropins (FSH and LH) from the anterior pituitary gland (APG).

• Ovaries: Produce estrogens (e.g., estradiol) and progesterone (steroids).

  • Estrogens: Maturation of reproductive organs, the appearance of secondary sex characteristics, and cyclic changes in the uterine lining.

  • With progesterone, estrogens cause breast development.

• Testes: Produce testosterone (steroid hormone).

  • Testosterone: Initiates maturation of male secondary sexual characteristics and sex drive, necessary for normal sperm production, and maintains reproductive organs in a functional state.

• Placenta: Secretes estrogen, progesterone, and human chorionic gonadotropin (hCG).

Hormone Secretion by Other Organs

• Adipose tissue: Releases leptin, resistin, and adiponectin.

  • Leptin: Released following ingestion of carbohydrates, targets cells in the sympathetic nervous system (SNS), reduces hunger, and increases energy expenditure.

  • Resistin: Insulin antagonist.

  • Adiponectin: Enhances sensitivity to insulin.

• Gastrointestinal (GI) tract: Enteroendocrine cells secrete hormones for digestion.

• Heart: Atrial natriuretic peptide (ANP). decreases blood [$Na^+$], thereby decreasing BP and blood volume and inhibits aldosterone secretion.

• Kidneys:

  • Erythropoietin: Signals the production of red blood cells (erythrocytes).

  • Renin: Initiates the renin-angiotensin-aldosterone mechanism.

• Skeleton

  • Osteocalcin: Signals the pancreas to secrete more insulin, restricts fat storage, improves glucose handling, and reduces body fat.

• Skin

  • Cholecalciferol: Precursor of vitamin D.

  • Calcitriol: Active form of vitamin D that helps absorb calcium from the intestine.

• Thymus:
  *Thymic hormones in normal development of T lymphocytes in response.

Developmental Aspects of the Endocrine System

Hormone-producing glands arise from all three germ layers.

Effects of Environmental Pollutants

Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function. Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants. Interference with glucocorticoids may help explain high cancer rates in certain areas.

Endocrine Function Throughout Life

Most endocrine organs operate well until old age. GH levels decrease with age, leading to muscle atrophy.

TH levels decrease with age, leading to lower basal metabolic rates. PTH levels remain constant, but the lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH. Glucose tolerance deteriorates with age. Testosterone also diminishes with age.