Main Function of Endocrine System
Uses chemical messengers to relay information and instructions between cells
Mechanisms of Intercellular Communication
1. Direct Communication
2. Paracrine Communication
3. Endocrine Communication
4. Synaptic Communication
Cell to cell communication / 1, 2, 3, GO!
Ex. In cardiac cells, coordinated response allows entire organ to contract at once instead of cell by cell.
Transmission: Through Gap Junctions; 1. Coord. ciliary movement, 2. Coord. contractions of cardiac muscle cells, 3. facilitate propagation of action potentials from one neuron to the next at electrical synapses.
Chem. Mediators: Ions, small solutes, lipid-soluble materials.
Distribution of Effects: Usually limited to adjacent cells of the same type interconnected by connexons.
Two cells communicate so closely that they function as single entity.
Cell to cell with in single tissue using chemical (paracrine factors/local hormones) messengers / 1:1 conversation.
Transmission: Through Extracellular Fluid
Chem. Mediators: Paracrine factors
Distribution of Effects: Primarily limited to local area, where paracrine factor concentrations are relatively high. Enter bloodstream but distant cells usually not affected. Some secondary effects in other tissues/organs. Target cells must have appropriate receptors.
Chemical messengers that are released in one tissue and transported via bloodstream to alter activities of specific cells in other tissues. Each hormone has "target cell"
Can diffuse out of their tissue and have widespread effects and hormones can affect their tissues of origin as well as distant cells. Different from hormone in that structure is unknown.
Specific cells that have appropriate receptors needed to bind and read hormonal message when it arrives. Each individual cell can respond to only a few of the hormones present.
Hormones travel via bloodstream to tissue at large. Activity of hormones in coordinating cellular activitiers in tissues in distant portions of body.
Chemical Mediators: Hormones
Distribution of Effects: Target cells are primarily in other tissues and organs and must have appropriate receptors.
How Hormones Work
1. Stimulate synthesis of enzyme or structural protein not already present in cytoplasm by activating appropriate genes in the cell nucleus.
2. Increase or decrease rate of synthesis of enzyme or protein by changing rate of transcription or translation.
3. Turn an existing enzyme or membrane channel on or off by changing its shape or structure.
Effects may be slow to appear but typically persist for days.
Hormones unable to handle situations requiring split-second responses - job of nervous system.
Transmission: Across synaptic clefts
Chemical Mediators: Neurotransmitters
Distribution of Effects: Limited to very specific area; target cells must have appropriate receptors.
Includes all endocrine cells and tissues of the body that produce hormones or paracrine factors with effects beyond their tissues of origin.
Glandular secretory cells that release their secretions into the extracellular fluid. Ductless.
Classes of Hormones by Chemical Structure
1. Amino Acid Derivatives: Synthesized from amino acids tyrosine and tryptophan. Tyrosine hormones include (a) thyroid hormones, (b) compounds epinephrine, norepinephrine, and dopamine (catecholamines). Primary hormone made from Tryptophan is melatonin.
2. Peptide Hormones: two groups; (a) glycoproteins, (b) short polypeptides and small proteins.
3. Lipid Derivatives: Two classes; (a) Eicosanoids - signaling molecules that include leukotrienes, prostaglandins, thromboxanes, and prostacyclins. (b) Steriod Hormones - lipids that are structurally similar to cholesterol. Individual hormones differ in side chains attached to basic ring structure. Liver gradually absorbs steroids and converts to soluble form that excreting in bile or urine.
Organs of Endocrine System
Pancreas (Pancreatic Islets)
Secondary Endocrine Functions:
3 Ways Hormones are Inactivated
1. Hormone diffuses out of the bloodstream and binds to receptors on target cells.
2. Hormone is absorbed and broken down by cells of liver or kidneys.
3. Hormone is broken down by enzymes in plasma or interstitial fluids.
Action of Hormones
Hormones coordinate cell, tissue, and organ activities on sustained basis.
Circulate in extracellular fluid and bind to specific receptors on/in target cells. They then modify cellular activities by altering membrane permeability, activating or inactivating key enzymes, or changing genetic activity.
To affect target cell, hormone must first interact with an appropriate receptor located either on plasma membrane or inside cell.
Receptors for catecholamines (E, NE, and dopamine), and peptide hormones
Receptors located in plasma membranes of target cells. Catecholamines and peptide hormones cannot penetrate a plasma membrane because they are not lipid soluble. these hormones bind to receptor proteins at the outer suface of plasma membrane (extracellular receptors). Hormones that bind to receptors in plama membrane cannot directly affect activities inside target cell.
Receptors for Eicosanoids
Receptors proteins on inner surface of membrane (intracellular receptors) because Eicosanoids are lipid soluble. They diffuse across the plasma membrane to reach receptor proteins.
Binds to extracellular receptors that leads to appearance of second messenger in cytoplasm.
Triggered by appearance of first messenger binding to extracellular receptors may act as enzyme activator, inhibitor, or cofactor. Net result is change in rates of carious metabolic reactions.
Most important second messengers are (1) cyclic-AMP (cAMP), a derivative of ATP; (2) cyclic-GMP (cGMP), a derivative of GTP, another high-energy compound; and (3) calcium ions.
Magnifies effect of hormone on target cells.
When small number of hormone molecules binds to membrane receptors, thousands of second messengers may appear in cell.
A linked sequence of enzymatic reactions.
Occurs when arrival of single hormone promotes release of more than one type of second messenger.
Process in which the presence of a hormone triggers a decrease in the number of hormone receptors.
When levels of a particular hormone are high, cells become less sensitive.
Process in which absence of a hormone triggers an increase in the number of hormone receptors.
When levels of a particular hormone are low, cells become more sensitive to it.
The link between first and second messengers.
An enzyme complex coupled to a membrane receptor.
Proteins bind GTP.
Activated when hormone binds to its receptor at the membrane surfaces.
~ 80% of prescription drugs target receptors coupled to G Proteins
Increasing cAMP Levels
1. Activated G Protein activates enzyme adenylate cyclase.
2. Adenylate cyclase converts ATP to ring-shaped molecule cyclic-AMP (cAMP).
3. cAMP then functions as second messenger, typically by activating a kinase (attaches high-energy P group) in phosphorylation.
4. Effect on target cells depends on nature of proteins (kinase). May open ion channels, release glucose from glycogen, etc.
*Increase usually short-lived because phosphodiesterase (PDE) inactivates cAPM by converting it back to CMP)
Hormones that Produce Effects my Increasing cAMP Levels
Lowering cAMP Levels
1. Activated G Protein stimulates PDE activity and inhibits adenylate cyclase activity.
2. Levels of cAMP then decline, because cAMP breakdown accelerates while cAMP synthesis is prevented.
*Decline has inhibitory effect on cell.
*Responsible for inhibitory effects that follow when epinephrine and norepinephrine stimulate Alpha2 adrenergic receptors.
G Proteins and Calcium Ions
1. Activated G Protein can trigger either opening of calcium ion channels in plasma membrane or release of calcium ions from intracellular compartments.
2. G Protein first activates enzyme phopholipace C (PLC) which triggers a receptor cascade that begins with production of diacylglycerol (DAG) and inositol triphosphate (IP3) from membrane phospholipids.
3. IP3 diffuses into cytoplasm and triggers release of Ca2+ from intracellular reserves.
4. Combination of DAG and intracellular calcium ions activates another membrane protein: protein kinase C (PKC). This leads to phosphorylation of calcium channel proteins, a process that opens the channels and permits extracellular Ca2+ to enter cell. This sets up positive feedback loop that rapidly elevates intracellular calcium ion concentrations.
5. calcium ions themselves serve as messengers, generally in combination with an intracellular protein (calmodulin). Once calmodulin has bound calcium ions, it can activate specific cytoplasmic enzymes. Chain of events responsible for stimulatory effects that follow when epinephrine or norepinephrine activates Alpha1 receptors.
Also involved in responses to OXT and other regulatory hormones secreted by Hypothalamus.
Functional counterparts of neural reflexes.
Sense change in physiology and secretory cells and immediately react.
1. Humoral Stimuli: changes in composition of extracellular fluid.
2. Hormonal Stimuli: Arrival or removal of specific hormone
3. Neural Stimuli: Arrival of neurotransmitters at neuroglandular junctions.
Controlled by negative feedback.
Simple Endocrine Reflex
Involves only one hormone. Endocrine cells involved respond directly to changes in the composition of the extracellular fluid. Secreted hormone adjusts the activities of target cells and restores hemeostasis. Controls hormone secretion by heart, pancreas, parathyroid, and digestive tract.
One Hormone/One Pathyway
Complex Endocrine Reflex
Involves one or more intermediary steps and two or more hormones.
Multiple Hormones/Intermediate Steps
the Big Daddy!!! Highest level of endocrine control. Weds neuro and chemical responses = neuroendocrine reflexes. Responds to changes in composition of circulating blood.
Integrates activities in 3 ways:
1. Acts as endocrine organ. Neurons synthesize hormones (ADH, oxytocin) and transport them along axons to posterior lobe of pituitary where they are released in to circulation.
2. Secretes regulatory hormones that control endocrine cells in anterior pituitary.
3. Contains autonomic centers that exert direct neural control over endocrine cells of adrenal medullae. When sympathetic division is activated, adrenal medullae release hormones into bloodstream.
Small oval gland nestled within sella turcica and hangs inferior to hypothalamus. Connected by infundibulum and held in position by sellar diaphragm. Consists of two lobes: adenohypophysis and neurohypophysis (anterior/posterior) that differ in functions.
Structure of Anterior Lobe/Adenohypophysis
1. Pars Distalis - The largest and most anterior portion of pituitary gland.
2. Pars Tuberalis - An extension which wraps around the adjacent portion of the infundibulum.
3. Pars Intermedia - Slender, narrow band bordering the posterior lobe.
Extensive capillary network radiate through regions giving endocrine cells immediate access to bloodstream.
Hypophyseal Portal System
Hypothalamic neurons release regulatory factors into the surrounding interstitial fluids at the median eminence (a swelling near the attachment of the infudibulum). Secretions easily enter bloodstream because of unusually permeable capillaries.
Capillary networks supplied by superior hypophyseal artery.
Vascular arrangement unusual because it carries blood from one capillary network to another without first visiting the heart.
Portal system contains histological structure of veins therefore are referred to portal veins.System ensures hormones entering portal vessels reach target cells in anterior lobe before being diluted through mixing with general circulation. Communication is strictly one way.
Unusually permeable capillaries that allow relatively large molecules to enter or leave bloodstream.
Hypothalamic Control of Anterior Lobe
Releasing Hormones (RH) stimulate synthesis and secretion of one or more hormones at anterior lobe.
Inhibiting Hormones (IH) prevent synthesis and secretion of hormones from anterior lobe.
Negative feedback controls rate at which hypothalamus secretes regulatory hormones.
Pituitary Hormonal Hierarchy
1. RH/IH come from hypothalamus and target pituitary secreting cells sending initial signals.
2. Tropic Hormones - Hormones made by pituitary and target downstream glands
3. Effector Hormones - Hormones made by specific target glands and will target effector tissues.
Hormones of Pituitary Anterior Lobe/Adenohypophysis
ACTH - Adrenocorticotropic Hormone
TSH - Thyroid-Stimulating Hormone
GH - Growth Hormone/Somatotropin
PRL - Prolactin
(a) FSH - Follicle-Stimulating Hormone
(b) LH - Luteinizing Hormone
MSH - Melanocyte-Stimulating Hormone
Thyroid-Stimulating Hormone (TSH) / Thyrotropin
Produced in adenohypophysis and target thyroid gland. Triggers release of thyroid hormones.
Released in response to thyrotropin-releasing hormone (TRH) from hypothalamus.
Stimulates ion pumps.
Adrenocorticotropic Hormone (ACTH) / Corticotropin
Produced in adenohypophysis.
Stimulates the release of steroid hormones by adrenal cortex.
Specifically targets cells that produce glucocorticoids (glucose metabolism)
Released under stimulation of corticotropin-releasing hormone (CRH) from hypopthalamus.
Follicle-Stimulating Hormone (FSH) / Follitropin
Produced in adenohypophysis.
Promotes follicle development in females and in combination with luteinizing hormone, stimulates secretion of estrogens by ovarian cells (Estradiol = most important).
In males, FSH stimulates nurse cells in seminiferous tubules where sperm differentiate. Nurse cells promote physical maturation of developing sperm.
FSH production inhibited by inhibin, a peptide hormone released by cells in testes and ovaries.
Luteinizing Hormone (LH) / Lutropin
Produced in adenohypophysis.
Induces ovulation and promotes secretion, by ovaries, of estrogens and progestins which prepare body for possible pregnancy.
In males, sometimes called interstitial cell-stimulating hormome (ICSH) because it stimulates production of sex hormones by interstitial cells of testes.
Male Hormones = Androgens - most important = testosterone.
Stimulated by GnRH from hypothalamus. Estrogens, progestins, and androgens inhibit GnRH production.
Prolactin (PRL0 / Mammotropin
Produced in adenohypophysis.
Works with other hormones to stimulate mammary gland development. Also stimulates mild production by mammary glands. Milk ejection occurs only in response to OXT release at neurohypophysis.
Functions of PRL in males are poorly understood but possible helps regulate androgen production by making interstitial cells more sensitive to LH.
Inhibited by neurotransmitter dopamine/prolactin-inhibitin hormone (PIH).
Hypothalamus also secretes several prolactin-releaseing factors (PRF).
Circulating PRL stimulates PIH release and inhibits secretion of PRF.
Growth Hormome (GH) / Somatotropin
Produced in adenohypophysis.
Stimulates cell growth and replication by accelerating rate of protein synthesis. Skeletal muscle cells and chondrocytes (cartilage) are particularly sensitive to GH.
Stimulation involves two mechanisms:
1. Indirect Primary Mechanism - Liver cells respond to GH by synthesizing and releasing somatomedins (compounds that stimulate tissue growth) or Insulin-Like GF (IGFs).
Peptide hormones bind to receptors on variety of plasma membranes. In skeletal muschle, cartilage and other target cells, somatomedins increase uptake of jamino acids and their incorporation into new proteins.
Effects develop almost immediatly after GH is released. Particularly important after a meal. Cells can now obtain ATP through aerobic metabolism of glucose and aa's are readily available for protien synthesis.
2. Direct Actions of GH - appear after blood glucose and amino acid concentrations have returned to normal.
In epithelia and CT, GH stimulates stem cell divisions and differentiation of daughter cells.
In adipose tissue, GH stimulates breakdown of stored triglycerides which then release fatty acids into blood. As fatty acid levels rise, many tissues stop breaking down glucose to generate ATP and start breaking down fatty acids (Glucose-sparing effect).
In Liver, GH stimulates breakdown of glycogen reserves whch then release glucose into bloodstream. Blood glucose levels begin to climb (diabetogenic effect).
Regulated by Growth Hormone-Releasing Hormone (GH-RH / somatocrinin) and Growth Hormone-Inhibiting Hormone (GH-IH / somatostatin) from hypothalamus.
Inhibited by Somatomedins.
Melanocyte-Stimulating Hormone (MSH) / Melanotropin
Produced in adenohypophysis.
Pars Intermedia may secrete two forms. Pars Intermedia virtually nonfunctional in adults excepts during (1) fetal development, (2) in very yound children, (3) in pregnant women, and (4) in course of some diseases.
Stimulates melanocytes of skin, increasing production of melanin (brown, black, yellow-brown pigment).
Inhibited by Dopamine.
Important in control of skin pigmentation in fishes, amphibians, reptiles, and many mammals other than primates.
In humans, produced locally, within sun-exposed skin.
Pituitary Posterior Lobe / Neurohypophysis and Hormones
Contains axons of hypothalamic neurons.
Neurons of Supraoptic and Paraventricular Nuclei manufacture ADH and OXT. Stores and releases hormones. Supraoptic produces ADH which controls water balance. Paraventricular produces OXT which is important in reproduction.
these hormones move along axons in infundibulum to axon terminals, which end on basal membranes of capillaries in neurohypophysis. Travel by means of axoplasmic transport.
Antidiuretic Hormone (ADH) / Vasopressin (VP)
Produced in Supraoptic neurosecretory cells in neurohypophysis.
Released in response to variety of stimuli, usually a rise in solute concentration in blood or fall in blood volume/pressure.
Rise in solute concentration stimulates osmoreceptors in hypothalamus. They respond to change in osmotic concentration of body fluids then stimulate neurosecretory neurons that release ADH.
Primary Function: To decrease amount of water lost at kidneys.
In high concentration, ADH also causes vasoconstriction, increasing BP. Alcohol inhibits ADH release which is why people have to pee when drinking.
Produced in Paraventricular neurosecretory cells in neurohypophysis.
In women, stimulates smooth musccle contraction in uteran wall promoting labor and delivery. After delivery, promotes ejection of milk by stimulating contraction of myoepithial cells around secretory alveoli and ducts of mammary glands.
Trigger for normal labor and delivery is probably sudden rise in oxytocin levels at the uterus.
Functions in sexual activity: circulating concentrations of oxytocin rise during sexual arousal and peak at orgasm in both sexes. In men, stimulates smooth muscle contractions in walls of ductus deferens (sperm duct) and prostate gland. Actions may be important in emission.
Lies inferior to larynx and requires iodine for hormone synthesis. Curves across anterior surface of the trachea just inferior to thyroid cartilage. Two lobes of thyroid gland are united by slender connection called isthmus.
Hollow spheres lined by simple cuboidal epithelium in thyroid gland. Follicle cells surround a follicle cavity that hold a viscous colloid, a fluid containing large quantities of dissolved proteins. Network of capillaries surrounds each follicle delivering nutrients and regulatory hormone to glandular cells and accepting their secretory products and wastes. Produces T3 and T4 hormones.
Cuboidal epithelium surrounds cavity that holds viscous colloid.
Synthesize globular protein - thyroglobulin and secrete it into thecolloid of follicles.
Maintain intracellular concentrations of iodine many times higher than those in extracellular fluid.
Globular protein produced in follicle cells. Contain amino acid tyrosine (building block of thyroid hormones).
Thyroid Hormone Formation
1. Iodine absorbed from diet is delivered to Thyroid Gland via bloodstream. Iodine ions are actively transported into cytoplasm by TSH-sensitive carrier proteins in basement membrane of follicle cells.
2. Iodine ions (I-) diffuse to apical surface of each follicle cell and thyroid peroxidase converts to an activated form of iodine (I+). This reaction sequence also attaches one or two iodine ions to tyrosine portions of a thyroglobulin molecule within follicle cavity.
3. Tyrosine molecules with attached iodine ions become linked by covalent bonds, forming molecules of thyroid hormones that remain incorporated into thyroglobulin. Most likely carried out by thyroid peroxidase. Eventually, each molecule of thyroglobulin contains four to eight molecules of T3 or T4 or both. TSH is major factor controlling rate of thyroid hormone release into blood. TSH stimulates production of thyroglobulin and thyroid peroxidase as well as the release of hormones.
*Under influence of TSH, the following steps occur:
4. Follicle cells remove thyroglobulin from follicles by endocytosis.
5. Lysosomal enzymes break down thyroglobulin, and amino acids and thyroid hormones enter cytoplasm. Amino acids are then recycled and used to synthesize more thyroglobulin.
6. Released molecules of T3 and T4 diffuse across basement membrane and enter bloodstream. 90% of thyroid secretions is T4.
7. About 75% of T4 and 70% of T3 entering bloodstream become attached to thyroid-binding globulins (TBGs) - transport proteins. Most of the remaining T3 and T4 are attached to transthyretin / thyroid-binding prealbumin (TBPA). Very small amounts remain unbound and are free to diffuse into peripheral tissues.
Thyroid -Binding Globulins (TBGs)
Globular proteins in blood that bind and transport 75% of T4 and 70% of T3 in body.
Transthyretin (thyroid-binding prealbumin/TBPA) / Albumin
Binds most of remaining T3 and T4 molecules.
Functions of Thyroid Hormones
Hormones affect almost every cell in the body. They enter target cells by means of energy-dependent transport system and bind to receptors:
1. In cytoplasm - where hormones are held in storage unless intracellular levels of hormones decline.
2. On surfaces of mitochondria - where hormones increase rates of mitochondrial ATP production.
3. In nucleus - which activates genes that control synthesis of enzymes involved in energy transformation and utilization. Ex. Accelerated production of sodium-potassium ATPase.
Hormones also activate genes that code for enzymes involved in glycolysis and ATP production which increases metabolic rate of cell.