Endocrinology Study Guide PDF

Study Guide -- this is not a complete list. There may also be questions that are not directly presented in this guide. This includes possible, although would be minority of, questions from text. Endocrine = Greek endo = within (inside/internal) crinis = secrete "Internal Secretion" Endocrinology =...

Study Guide -- this is not a complete list. There may also be questions that are not directly presented in this guide. This includes possible, although would be minority of, questions from text. Endocrine = Greek endo = within (inside/internal) crinis = secrete "Internal Secretion" Endocrinology = study of internal secretions Original Definition. Misnomer as this would include non-endocrine I. History of Endocrinology -- A. Broken down into 3 periods Know what they mean and what they covered 1. Descriptive Period -- a. Started more that 5000 yrs ago b. Structures that could be observed in this period is -- testis and thyroid c. Chinese had a thyroid disorder --seaweed as treatment d. Eunuchs removal of testis in humans = people observed the effects of castration, such as the lack of secondary sexual characteristics, changes in voice, and differences in physical development 1\. Also done in some domestic animals e\. 1776 *Text book of Physiology* 1766 -- Dutch Physicians. Concept of Endocrine glands led to next period. 2. Period of Analytical Endocrinology = study of specific glands a. Arnold Berthold -Knew castration of young male chickens -- capon instead of rooster 1\. Studies of the effects-controlled experiments-- know what he did -- removal and replacement -- placement in body cavity and removal from one young chicken replaced in another 2.Demonstrated the role of testis in making roosters -- blood supply -- study not followed up. b\. Henle 1841 -ductless gland c\. 1855 -- The Great Year major publications in Endocrinology 1\. Triumvirate - **know what each one is known for**. a\. Charles-Édouard Brown-Séquard injected himself with blood form testicular veins, b\. Claude Bernard -- Father of Modern Physiology c\. Thomas Addison - role of adrenals in disease -- followed the progression d\. Victor Horsely and George Murry -- Horsely removal of thyroid produced conditions similar to human disease myxedema. Suggested could treat with extract from thyroid. His student George Murry produced PINK FLUID from Sheep thyroid and treated a woman. e. Harvey Cushing -- Master Gland Pituitary - 3. Contemporary Period/Synthetic Endocrinology -discovering and describing hormones. a. 1^st^ "hormone" described **secretin** , located in the duodenum - William Bayliss and Ernest **Starling** term hormone Greek = **ormao** = to excite/stir up. b. **Insulin** -Fredick Banting know why and what he did -- ligating dog pancreas and collecting fluid -- treating other dogs that had pancreas removed and developed diabetes. Then extracted from calves and final cows -- successfully treat child suffering from diabetes c. Eli Lilly -- produced Bovine insulin for commercial treatment d. 1951 Frederick Sanger -- sequenced Insulin -- 51 Amino Acids -- led to modern production of synthetic hormones 4. **Textbook Figure 1.17 -- Major figures and names from 19^th^ and 20^th^ century** in "endocrinology". Introduction/Overview of Hormones - the messengers of the endocrine system A. Classic Definition -- chemical messenger produced in an endocrine gland, secreted into the general circulation affecting a distant target cell -- affecting cellular function/physiology B. Regulate specific cells -- **Target cells** that must have **receptor** for specific hormone C. Functions -- metabolism and water/electrolyte balance 1.Play major roles in **Homeostasis, Growth, and Reproduction** D. Endocrine and Nervous systems work in concert -- **know information from TABLE** be able to compare the differences A table with text on it Description automatically generated E. Neurohormone -- similar action as hormone, but produced by neural tissue F. Classification -- **understand the following terms and be able to identify by example. Also understand that a hormone may be able to have more than one function** 1\. Prohormone -- chemical precursor for a hormone - a\. Splitting or removing -- creates an active hormone - The **pancreas (β-cells in the islets of Langerhans)** releases **insulin** into the bloodstream. tissue. Ex: **Example:** **Testosterone in the testes** - **Leydig cells** in the testes produce **testosterone** and release it. - Testosterone acts on nearby **Sertoli cells** to support sperm production - **Activated T-cells** produce **IL-2**, a cytokine. - IL-2 binds to receptors on the same T-cells that produced it. G. Effects of hormones are determined by multiple factors including 1. Concentration/level of the hormone 2. Carrier molecules (presences and amount) 3. Number of receptors 4. Affinity of receptors 5. Enzymes (presence/amount/type) 6. Co-factors 7. 7\. Inhibition by other hormones or compounds H. Also classified by chemical structure know **the general structure of each type be able to identify them** 1. Steroids (lipids -hydrophobic)  2. Eicosanoids (fatty acids)- Prostaglandins 3. Amino acid based -- a. Amines - mono or diamines produced from tryptophan or tyrosine b. Peptide (**Figure 4.6 text**) -- multiple animo acids, but no tertiary structures 1.examples include -- oxytocin and vasopressin 9 amino acids, and Gonadotrophin-releasing hormone (GnRH) 10 amino acids. c. Proteins -- tertiary structure multiple amino acids 1. Glycoproteins -- proteins with glycogen and 2 chains alpha and beta a. Alpha similar in all -- Beta the variable chain -- examples Follicle stimulating hormone (FSH), luteinizing hormone (LH) and chorionic gonadotrophin (CG) 2. Somatomammotrophic polypeptides -- not alpha and beta chains no glycogen -- a. Examples include prolactin and growth hormone 3. **Be able to identify the steps in figure on production, packing and cell release of protein hormones**. Also **Figure 4.9 text** Diagram of a diagram showing the process of a fertilization Description automatically generated Endocrine Glands -- Overview know the major endocrine glands, associated hormones produced (endocrine versus neurohormone) TABLE  Understanding glands -- **exocrine duct glands** derived from ectoderm-- sweat, mucus and milk, digestive enzymes vs **ductless endocrine glands** can be derived from **ectoderm, mesoderm or endoderm** A. Pineal -- in brain neural tissue B. Pituitary 1. Anterior -- endocrine tissue hormones 2. Posterior Pituitary- Synaptic terminal -- cell bodies in the brain PVN and SON C. Hypothalamus -- part of brain, produces many regulator/tropic hormones D. Thyroid -- iodine regulate metabolism E. Parathyroids -- calcium regulation embedded in thyroid F. Adrenal Gland 1. Medulla -- neural tissue epinephrine and norepinephrine. 2. Cortex -- endocrine -- primarily produces steroids G. Pancreas- insulin and glucagon H. Gonads -- produce sex steroids - 1. Different in male and female a. Female -- ovary produces progesterone, testosterone (prohormone not released) and estrogens b. Male -- testis -- primarily androgens (which include testosterone) I. **Other major organs/systems with Endocrine Function** 1. Heart- (ANP) - Increase Filtration rate decrease Na+ reabsorption, (BNP) -- produced by ventricles 2. Kidney- Renin - Increase Angiotensin-aldosterone system, Prostaglandins - decrease Na+ reabsorption 3. Gastrointestinal Tract- Gastrin - Secreted from stomach (G cells), role in control of gastric acid secretion Cholecystokinin - small intestine hormone, stimulates secretion of pancreatic enzymes and bile 4. Adipose tissue- Leptin - polypeptide hormone produced in adipose and many other tissues with also many different roles\ Adiponectin - regulation of energy homeostasis and glucose and lipid metabolism, as well as acting as an anti-inflammatory on the cellular vascular wall 5. Placenta -- during pregnancy in eutherian mammals one of the largest endocrine function. Regulation of Hormones A. Nervous system 1. Neurotransmitters stimulate or inhibit hormone release. B. Feedback loops hormone involved in form of self regulation 1. Positive -- hormone stimulates increasing levels (temporary cannot go on endlessly-- 2. Negative Feeback loop -- **know and understand examples** a. Simple -- hormone directly regulates itself (**example glucose regulation**) b. Complex regulation through tropic hormones (**example Figure 2.12 textbook**) Diagram of a diagram of a cell Description automatically generated C. Responses to hormones can be variable -- **see figure**, increasing till dose hits asymptote, unimodal, bimodal. D. Method of action --(see figures) 1. Targeting other endocrine glands versus regulating the function of other cells 2. Tropic can be releasing or inhibiting of other hormones. Ex: **Thyroid-Stimulating Hormone (TSH)**: Stimulates the thyroid gland to produce thyroid hormones Hormonal Signal Transduction -- hormone must act through receptor which initiates a response by target cell A. How the cell responds to the "signal" = signal transduction. B. **Receptors are proteins because** they have specificity of action such as active sites, that limits what a ligand can bind too. Proteins only bind to one hormone or a related hormone. 1. Binding causes configurational change 2. Compound that binds to a receptor = **ligand** a. Hormones are ligands, not all ligands are hormones. b. Types of Ligand actions c. Agonistic: binding of ligand promotes a change in the shape (conformation) of the receptor complex that promotes co-activation recruitment and gene transcription d. Antagonistic: binding of ligand promotes a different change in shape that recruits co-repressors and blocks gene transcription e. Mixed agonistic and antagonistic: based on the relative concentration of coactivator or corepressor in a particular tissue. 3. Bond between ligand and receptor - **Non-covalent** - Hydrogen, ionic, van der Waals. a. makes process reversible H = free unbound hormone R = free unbound receptor b. HR = hormone receptor complex (hormone bound to receptor) c. Critical how strong and how long determines affinity d. **Understand affinity Kd based upon ratio of Koff (H+R) and Kon (HR) see PPT and page 110 textbook**. e. the affinity  \- The smaller the number the higher the affinity. 4. Binding determined by multiple factors including a.\# of receptors b\. Affinity of receptor c\. Specificity of the ligand d\. amount of hormone, if below saturation point Receptors - A. Two major classes of receptors based upon where they are located 1. Membrane bound (binding site outside cell) a. Actions generally faster and involves 2^nd^ messenger 2. Cytoplasmic or nuclear -- receptor inside cell a. typically slower and involve direct gene activation B. Nuclear Receptor Family (number 2 above) 1. General Action: bind directly to DNA to regulate gene expression (Transcription factors) 2. Classical nuclear receptors only work after binding the ligand 3. **Know the structural regions A/B through F** (**textbook Figure 5.21**) A diagram of a structure Description automatically generated 1. Highlights A/B= N-terminal domain, C = DNA binding, D=hinge region E=ligand binding F 4. **Understand dimerization** -- hormone binds to receptor (Hormone receptor complex = HR). This means hormone binds to receptor then two individuals HR dimerize. a. Homodimer -- two of the same HRs b. Heterodimer -- one HR binds to a different receptor 5. Dimerized HR then binds to the Hormone Response Element (HRE) on DNA. Via the DNA binding sight on receptor 6. HRE -- hormone response element -- binding site on DNA consists of two half sites (dimerized HR -- so needs two halves to bind each part) **Be able to identify the following.** 1. Dependent upon three factors (Powerpoint and Fig 5.23 texbook) a. Sequence of base pairs in half-site b. Number of base pairs between half-sites (0, 3, variable) c. Orientation of half-site (palindrome inverted versus direct) 2.  3. STEROIDS: AGAACA\ THYROIDS/ ESTROGEN: AGGTCA 7. Action of Nuclear receptors -- dependent upon location (cytoplasm vs nucleus) and method of action. a. Type 1 -- (textbook Fig 5.19) HR complex forms in cytoplasm -forms homodimer- HR then transported into nucleus -- binds to HRE on DNA -- recruits co-activators -- stimulating transcription.Diagram of steroid receptors type i Description automatically generated b. Type 2 -- Receptor bound to HRE on DNA -- hormone enters and binds to receptor to make HR -releases co-repressor activating response 8.