Endocrinology_TEXT1 PDF

Homeostasis Nervous System Acts Rapidly (in milliseconds), but Short-lived Messenger = Electrical Signals → Neurotransmitters Very Specific receptor organs at the end of each neuron May Stim/Inh release of Hormones Primarily cause Musc. Ctx & secre...

Homeostasis Nervous System Acts Rapidly (in milliseconds), but Short-lived Messenger = Electrical Signals → Neurotransmitters Very Specific receptor organs at the end of each neuron May Stim/Inh release of Hormones Primarily cause Musc. Ctx & secretion of fluids from glands Endocrine System Acts Slowly (seconds to hours), but Long-lived Messenger = Hormones (Chemicals) Less Specific via Blood Stream to all Body cells Some hormones may Stim/Inh Nerve impulses Some hormones (Epi./NE) may be Neurotransmitters also and act in other target cells  Basic Concepts of Endocrine System Functions to keep the body in Homeostasis A state of equilibrium Keeps the body in a steady & balanced state so that the body systems can function optimally Involves: Body fluids Acid-base balance Temperature Metabolism Other factors  Endocrine Organs Hypothalamus Thymus Pineal Gland Pancreas Pituitary Gland Adrenal (Suprarenal) Glands Posterior Pituitary Adrenal Cortex Anterior Pituitary Adrenal Medulla Thyroid Gland Ovaries Parathyroid Glands Testes Hypothalamic-Pituitary-Target gland Axis Hypothalamus Produces Releasing and Inhibiting Hormones Stimulates Anterior Pituitary Gland Anterior Pituitary Gland Produces Stimulating Hormones Stimulates different “Target Organs” “Target Organs” Release their own Hormones  Intercellular Chemical Signals Hormones Released by endocrine glands Enter circulatory system Affect distant cells Ex.: Estrogen Autocrine Released by cells and have a local effect on same cell type from which chemical signals released Do NOT enter the blood Ex.: Prostaglandin Paracrine Released by cells and affect other neighborly cell types locally without being transported in blood Ex.: Somatostatin  Pheromones Secreted into environment and modify behavior and physiology Ex.: Sex pheromones Neurohormone Produced by neurons and function like hormones Mostly from Post. Pituitary Gland Ex.: Oxytocin & ADH Neurotransmitter or Neuromodulator Produced by neurons Secreted into extracellular spaces by presynaptic nerve terminals Travels short distances Influences postsynaptic cells Ex.: Acetylcholine. Locally-acting Chemicals – Do NOT enter the Blood Paracrine (“Para” = near) – Act upon cells next to secreting cells Autocrine (“Auto” = self) – Act upon the cell that secreted it In contrast… Other hormones may circulate for hrs & their effect being lost once inactivated or secreted  Hormonal Secretion 3 Patterns of Regulation of Hormone Secretion 1. Neural via Autonomic Nervous System (Ex.: Stress) 2. Non-Hormonal via concentration of a substance (Ex.: Glucose) 3. Hormonal via concentration of a hormone (Ex.: Thyroid hormones)  1. Nervous System Regulation Stimuli such as stress or exercise activate the sympathetic division of the autonomic nervous system Sympathetic neurons stimulate the release of epinephrine and smaller amounts of norepinephrine from the adrenal medulla. Epinephrine and norepinephrine prepare the body to respond to stressful conditions. Once the stressful stimuli are removed, less epinephrine is released as a result of decreased stimulation from the autonomic nervous system. 2. Action of Substance Other Than Hormone An increased blood glucose concentration stimulates increased insulin secretion from the pancreas Insulin increases glucose uptake by tissues, which decreases blood glucose levels. Autonomic nervous system also influences insulin secretion  3. Hormonal Regulation Negative and Positive Feedback At each level of the HPT Axis Prevents Over-secretion of any hormone Acts like a “Thermostat” of a house Stimulation (+) Inhibition (-) Homeostasis Values of variables fluctuate around a SET POINT This determines a normal range of values SET POINT Desired value What is the set point for Body Temperature? Negative Feedback Any deviation ( or ) from the set point is made SMALLER (ie.: Returning to normalcy) This occurs mostly in the body Positive Feedback Any deviation ( or ) from the set point is made GREATER (ie.: Going further away from normalcy) Not so common in the body  Transport & Distribution Hormones dissolve in blood 2 forms in bloodstream 1. Free Form 2. Bound to Binding Protein, reversibly Equilibrium of 2 forms Hormones distributed quickly thru body because they are in the blood Free Form Diffuse thru Capillary wall into Interstitial Fluid Follows concentration gradient Lipid-soluble Hormones Diffuse easily thru Capillary Cells Water-soluble Hormones Must pass thru Capillary Fenestrae Bound Form Reversibly bound as a “Reserve” on Binding Proteins (In Proteinuria, the Pt will lose these binding proteins in his urine and thus the hormone bound to them) Hormone/Target Cell Interaction Ligand Anything that binds to a receptor ie.: A Hormone is a Ligand Binding Site Where the Ligand binds to ie.: A Receptor Site is a Binding Site Ligand/Binding Site A proper connection will elicit a response by the Target Cell VERY SPECIFIC ie.: GH cannot bind to an Oxytocin Receptor site  Target Cells Highly specific receptors (proteins or glycoproteins) Geometry of receptors complement specific hormone Like a “Lock & Key” fit Up Regulation -  Sensitivity when Low Hormone level Down Regulation -  Sensitivity when High Hormone level  Receptors for Hormones Receptors for Catecholamines & Peptide Hormones are in the cell membranes of target cells Thyroid & Steroid Hormones cross the membrane and bind to receptors in the cytoplasm or nucleus  Classes of Receptors Membrane-bound Receptors Integral proteins with receptor site at cell surface These do NOT enter cell Interact with ligands that cannot pass through the plasma membrane Involves a 2nd Messenger within the cell a “Chain Reaction” occurs Ligands: – Water-soluble, Larger ligands, etc. Protein Hormones Polypeptide Hormones Catecholamines (Epi/NE) Intracellular Receptors In cytoplasm or in the nucleus These DO enter cell Interact with ligands that can pass through the plasma membrane Ligands: – Lipid-soluble, Smaller ligands, etc. Steroid Hormones Thyroid Hormones  Membrane-bound Receptors Ligand binds reversibly 1 of 2 Cascade of Events occurs: 1. Activation of G proteins  cAMP, Ca2+, Diacylglycerol (DAG) or Inositol Triphosphate (IP3) 2. Receptors Alter Activity of Intracellular Enzymes Directly  cGMP, Nitric oxide, or Ca2+  1. Activation of G Proteins Cascade of Events for  cAMP: 1. Hormone (1st Messenger) binds to “Surface Receptor” 2. This then binds to a G protein in the cell 3. The G protein is then activated as it binds GTP, displacing GDP 4. Adenylate Cyclase is activated 5. This produces cAMP (2nd Messenger) in cell 6. cAMP binds to Protein Kinase 7. Phosphorylation occurs on certain Proteins (requires ATP) 8. Activation of those Proteins occurs (ie.: the protein is made in response to what hormone “told” the cell) – 1 hormone molecule will activate a chain of cascades resulting in millions of activated proteins which, in turn, make billions of the substance the protein is suppose to release This is why it responds RAPIDLY !!!! Other 2nd Messengers: Ca2+ Diacylglycerol (DAG) Inositol Triphosphate (IP3) Understand cAMP’s mechanism (illustrated in the past few slides) Don’t worry about the mechanisms of other 2nd messengers You can view the next 3 Diagrams to see how other 2nd messenger mechanisms occur…… Notice the chain of events BEFORE the 2nd messenger begins are the same as with cAMP’s mechanism 2. Receptors that Directly Alter the Activity of Intracellular Enzymes (Simpler Cascade as G-Protein is NOT involved) Cascade of Events for  cGMP 1. Hormone (1st Messenger) binds to “Surface Receptor” 2. The inner portion of this receptor activates Guanylate cyclase 3. This converts GTP to cGMP (2nd Messenger) 4. cGMP acts on certain Proteins 5. Activation of those Proteins occurs Phosphodiesterase inactivates cGMP to GMP This Pathway also responds RAPIDLY !!!!  Intracellular Receptors Thyroid & Steroid Hormones > 90% are bound to proteins in blood These hormones diffuse into target cells Binds to DNA in Nucleus A specific mRNA is made and synthesizes a certain protein that the hormone “tells” the target cell to make There is no amplification (ie.: 1 structure does not tell 4 structures what to do at the same time) This is why it responds SLOWLY !!!  Hypothalamus (Neural Functions) Coordinates HR, BP & Resp. rate from: Pons Medulla oblongata Regulates: Temperature Hunger / Thirst Sleep Endocrine Functions……… Where the Nervous & Endocrine Systems interact Releasing & Inhibiting Hormones 7 Major Hormones (Ex. TRH, GnRH, PIH, etc.) Synthesized, Stored AND Secreted by Hypothalamus Target Organ is Anterior Pituitary Gland ADH & Oxytocin Synthesized by Hypothalamus Stored & Secreted by Posterior Pituitary Gland May still find their way into the bloodstream if the Posterior Pituitary Gland is compromised since they are still both synthesized  Pineal Gland (Body) Circadium Rhythm Biological Clock “Jet Lag” issue Releases Melatonin (NOT Melanin) Daylight (-) / Darkness (+) May control Onset of Puberty?? Melatonin ’s during puberty Pituitary Gland (Hypophysis) “The Master Gland” Sits in Sella Turcica Bony “cup” in the sphenoid bone Actually Two (2) Glands: 1. Anterior Pituitary Gland (Adenohypophysis) – Synthesizes, Stores & Secretes 7 Major Hormones from itself into bloodstream – 75% of Pituitary – Evolved from floor of mouth (Rathke’s Pouch) 2. Posterior Pituitary Gland (Neurohypophysis) – Stores and Secretes 2 hormones (*** These are actually synthesized in Hypothalamus) – Evolved from base of brain An “Extension” of the Hypothalamus via Infundibulum  Anterior Pituitary Gland (Histology) Acidophils (Pinkish) Cells that contain Polypeptide Hormones Somatotropes which produce GH Lactotropes which produce PRL Basophils (Bluish) Cells that contain Glycoprotein Hormones Thyrotropes which produce TSH Gonadotropes which produce LH or FSH Corticotropes which produce ACTH Chromophobes (Colorless) These are cells that have minimal or no hormonal content Anterior Pituitary Gland Hormones Thyroid Stimulating Hormone (TSH) Stimulates thyroid gland to secrete thyroid hormones (T 3 & T4) Growth Hormone (GH) Stimulates most tissues to grow Adrenocorticotropic Hormone (ACTH) Stimulates adrenal (cortex) gland to secrete its hormones (mostly Cortisol) Follicle Stimulating Hormone (FSH) Stimulates follicles (egg sacs) to grow in ovaries Stimulates sperm production in testicles Luteinizing Hormone (LH) Releases progesterone from ovaries AND Triggers ovulation (release of egg from ovary) Releases testosterone from testicles Prolactin (PRL) Stimulates breasts to make milk Melanocyte Stimulating Hormone (MSH) Stimulates melanocytes to secrete melanin  Posterior Pituitary Gland (Histology) Neuroglia Pituicytes Nerve fibers (Axons) Fenestrated Capillaries “Little holes” to allow the hormones to enter blood Posterior Pituitary Gland Hormones Anti-Diuretic Hormone (ADH)  Urine →  Blood volume →  BP Oxytocin (OXY) Ejects milk from breasts Contracts uterus during labor  ANTERIOR Pituitary Gland Tropic Hormones (Tropins) All Anterior Pituitary Hormones are tropins Regulate hormone secretions of target endocrine tissues  ANTERIOR Pituitary Gland 1. Growth Hormone (GH) (a.k.a. Somatotropin) *** Stimulates Cell Growth in all body cells (Increases Height & Weight in Puberty) Excess – (Symptoms differ if Growth plates are fused or not) Gigantism – (In Children) – Symmetrical growth of long bones Growth plates are NOT fused yet Acromegaly – (In Adults) – Facial features become wider & enlarged Growth plates are already fused – Enlarged Hands, Face & Jaw – HTN – Death due to Heart Failure Pituitary Gland lies adjacent to Optic Chiasm Large Pituitary Tumor can press against Optic Chiasm Causes “Tunnel Vision” (Bitemporal Hemianopsia) (Inferior View)  Deficiency – Pituitary Dwarfism (In Children) Short stature, but with normal body proportions Growth plates are NOT fused yet NOTE: Not all causes of Dwarfism are due to GH deficiency.  Dwarfism ACHONDROPLASIA – (m.c. form of Dwarfism (70%)) Long bones stop growing in childhood Normal torso, short limbs Failure of cartilage growth in Epiphyseal Plate Spontaneous mutation produces mutant dominant allele PITUITARY DWARFISM Lack of Growth Hormone (GH) Normal proportions with short stature 2. Thyroid Stimulating Hormone (TSH) (a.k.a. Thyrotropin) Stimulates Thyroid gland to secrete Thyroid Hormones T3 T4 3. Adrenocorticotropic Hormone (ACTH) Stimulates Adrenal (Cortex) gland to secrete 3 Hormones: Aldosterone Cortisol Androgens (Sex Steroids (Testosterone & Estrogen)) Binds directly to Melanocytes and releases Melanin 4. Follicle Stimulating Hormone (FSH) In Females (acts on Ovaries) Develops Follicles Produces Mature Ova Secretes Estrogen In Males (acts on Testes) Stimulates Production of Sperm 5. Luteinizing Hormone (LH) In Females (acts on Ovaries) Triggers Ovulation Stimulates Corpus Luteum to secrete Progesterone (Corpus Luteum → ruptured site where egg was released) In Males (acts on Testes) Secretes Testosterone 6. Prolactin (PRL) Stimulates the Development of Milk Glands (During Puberty) Stimulates the Production of Milk (During Pregnancy) 7. Melanocyte Stimulating Hormone (MSH) Not truly a significant hormone NOT produced in adults In Pregnancy: Stimulates Melanocytes in skin to release Melanin (Produces Pigmentation in face & Abdomen) ACTH also stimulates Melanocytes  POSTERIOR Pituitary Gland 1. Antidiuretic Hormone (ADH, Vasopressin) Reabsorbs H2O from Kidneys  Urine Volume →  Blood volume →  BP  Vasoconstriction →  BV Diameter →  BP Excess Syndrome of Inappropriate ADH (SIADH) – Lung Cancer (m.c.c.) → Produces an ADH-like hormone    Urine →    Blood volume → HTN    Vasoconstriction →    BV Diameter → HTN Deficiency Diabetes Insipidus (DI)    Urine →    Blood volume → HYPOtension VERY Rare POLYDIPSIA = Increase in Thirst POLYURIA = Increase in Urine output 2. Oxytocin Stimulates Uterus to contract Begins labor Stimulates the Release of Milk (Lactation) When baby cries or sucks