BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/14/2012, 1st hour Page1 Announcements: Office hours - Add Tuesdays 8:30-11AM to notes, but already in syllabus Paper - Will send out topics tomorrow - Have 3 weeks to complete Start off with endocrine system then finish with GI No more in class lecture reviews, will send out an outline instead Lecture 1 Intro to Endocrine System Endocrine communication system - Sending signals from one organ to elicit a response in other organs - A number of specialized glands to release hormones into circulation that can influence organs at distant tissues o Endocrine, influence tissue at a distant location o Paracrine, influence tissue at close vicinity (local tissue) o Autocrine, some cells release hormone that will act upon itself o Primarily hormones will be the endocrine type - Onset of action varies from seconds (EPI, epinephrine) to very long periods of time (thyroxine) such as months - Effective concentrations are very small (from 10-12 to 10-6 g/ml of blood) o A little goes a long way, do not need a lot to elicit a fairly significant effect o Hormones are secreted in minimal quantities Endocrine Glands - All over the body Hormone system - Defintion: A group of hormones or endocrine organs involved in stimulating and the release of a single hormone - Hypothalamus, anterior pituitary and thyroid gland – play role in stimulating the release of thyroid hormone from thyroid gland o These organs function together as a system to get same end result: thyroid hormone release/secretion - These organs still secrete other hormones responsible for other tissues, as noted in the diagram below BHS 116.2 – Physiology Notetaker: Vivien Yip - Date: 11/14/2012, 1st hour Page2 Play key roles in regulating bodily functions such as: o o o o o Metabolism Growth and development Water and electrolyte balance Reproduction Behavior Describe the different types of hormones, their characteristics (Table 4-4), and how they are synthesized. [Info from Lectures 1 & 2] - Proteins - Steroids - Tyrosine derivatives 3 primary types of hormones - Proteins (more than or equal to 100 amino acids) o Smaller proteins = peptides (less than 100 amino acids) - Steroids - Tyrosine derivatives (amines) - Sherwood Tables 4-4 & 18-2, comprehensive list of types of hormones, what they do, structure, function, target tissues, good source of information, but will be covered throughout quarter Protein/Peptide Hormones - Same synthetic process as any other protein would in the body - Endocrine cell produces these - Largest category of hormones Overview of production: 1. Synthesis: - Transcription - Translation 2. Packaging (golgi) 3. Storage (in vesicles) 4. When endocrine cell is stimulated, 2nd messengers are activated and trigger secretion of hormone Protein/Peptide Hormone Production Synthesized as larger inactive proteins called preprohormones - Inactive form of hormone - All start out in this form In ER, - Preprohormones are converted to prohormones and cleaved off - Inactive form of hormones In Golgi, - Prohormones are concentrated and packaged - Sent off to secretory vesicles - Prohormones undergo reaction and cleaved will be active (occurs inside vesicle) - Vesicles contain inactive fragments and active hormones BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/14/2012, 1st hour Page3 - Inactive fragments have some biological function - Stored in secretory vesicles until needed When endocrine cell is activated - Vesicle fuses with plasma membrane, active hormones are released via exocytosis - Inactive fragments also released o Most are biologically inactive, but there are instances where some of them do have biological activity (will learn more about later) Protein/Peptide hormones - Water soluble - Directly dissolve in blood circulation - Do not require carrier - Carried off to another part of the body to act on organs Steroid Hormones - Derived from cholesterol, back bone - Three cyclohexyl rings - One cyclopentyl ring - Don’t worry about structure (not tested) Steroid hormone synthetic pathways - Only the cells that make a specific hormone will contain the enzymes necessary to make that steroid hormone Cholesterol o Specific set of enzymes will turn that cholesterol into progesterone o Progesterone is further modified to aldosterone or estrogen precursor o Only that specific group of cells that make a specific hormone will have the necessary enzymes to make that specific hormone o Not all endocrine producing cells have all the various enzymes to make all the steroid hormones o Example: Specific group of cells have enzymes necessary to convert cholesterol to testosterone, (not the same enzymes to make aldosterone or cortisol) BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/14/2012, 1st hour Page4 o Just because it is a steroid producing endocrine organ, does not mean they all have ability to make any type of steroid hormone, only have specific enzymes for specific steroid hormones Steroid hormone storage - Very little steroid hormone storage o Have large store of cholesterol o Can be rapidly converted to the steroid hormone if needed - Do not need to make and store hormone itself - Does not have to go through the protein synthetic process (takes a lot longer) - Not water soluble, lipid soluble - Do not readily dissolve in blood - Require plasma proteins for transport to their target organs - Once the steroid hormones are synthesized, they simply diffuse out of the cell into the interstitial fluid eventually reaching the blood where they bind plasma proteins Tyrosine derived hormones/Amines 2 groups - Thyroid hormones - Catecholamines, EPI, NEPI, adrenal medullary hormones o Both formed from tyrosine (backbone) o Just like cholesterol was back bone of steroid hormones Catecholamines, Adrenal Medullary Hormones Thyroid hormones Made in thyroid gland Made in adrenal medulla Incorporated into large macromolecules called Epinephrine, norepinephrine thyroglobulin (giant chain with amines) Taken up into preformed vesicles and stored until When thyroid cell is stimulated, thyroid hormones exocytosed are released from thyroglobulin Thyroid hormones are stored in follicles Lipid soluble Water soluble Require thyroxine binding globulin (plasma Freely dissolve into blood plasma and do not protein) to be carried to target tissue, slow release require plasma proteins to get to target tissue of hormone Hormone Summary Chart Protein Water Soluble, no carrier req’d Transcription, translation, packaging, storage, stimulation for release Steroid Lipid soluble, req carrier Cholesterol based backbone Tyrosine derivatives/Amine Thyroid hormones – lipid soluble Catecholamines – water soluble Tyrosine based backbone Describe the concepts of negative and positive feedback Negative feedback - Endocrine system is driven by negative feedback control of hormone secretion - Once the end result is produced, once our hormone is made, that hormone will negatively feedback on the tissues that are stimulating its production and prevent further hormone secretion and synthesis BHS 116.2 – Physiology Notetaker: Vivien Yip - Date: 11/14/2012, 1st hour Page5 A little bit goes a long way Once hormone is secreted, we do not need anymore made, only require a little to be produced Our end result (hormone) is going to counteract more hormone production Regulation occurs at all levels of hormone production:transcription, translation, processing and secretion Positive feedback - Few instances - Estrogen is produced and secreted - Stimulate anterior pituitary to produce more LH - Stimulate ovaries to produce more estrogen - Estrogen production is going to feedback more estrogen production - Opposite of negative feedback Negative feedback example - Endocrine system is primarily driven by negative feedback - Hypothalamus pituitary system - Hormone released to stimulate anterior pituitary to be released - Targets endocrine gland - Endocrine gland produces target hormone - That hormone will feedback to the anterior pituitary and inhibit further secretion of that hormone - In most instances it will negatively feedback the hypothalamus and prevent further secretion of that hormone Positive Feedback Example Estrogen - Further stimulate more LH, stimulating more estrogen release Cyclical Variations - Do not need to be stimulated by any specific stimulus - Will be released at specific point of time - Circadian/Diurnal, daily - Seasonal, primarily seen in lower mammals during mating season - Sleep - Age or development, automatically the organs are programmed to release them Example: Diurnal variation in cortisol - Peaks during night and day - Lowest levels at night, starting rising as we sleep - Peak when we wake up in the morning - Go through cycle on their own - Organ will release cortisol on its own - Most of these organs are also sensitive to other stimuli BHS 116.2 – Physiology Notetaker: Vivien Yip - Date: 11/14/2012, 1st hour Page6 Can get peaks of cortisol in middle of the day if the organ is stimulated Normally has its own normal rhythm and released with its own cycle Describe how the concentration of hormones in the blood is regulated (secretion, activation, binding, excretion) 2 regulating factors of concentration of hormones in the blood Major factor: rate of secretion into blood Secondary factor: rate of removal of hormones from the circulation (metabolic clearance rate) Metabolic clearance rate: volume of blood completely cleared of hormone or drug per unit time (ml/min) - Remove hormone in a number of different ways: o Binding w/ tissue, removed by binding to target o Metabolically destroyed by target tissue o Inactivation and excretion by liver into the bile o Excreted by kidneys in urine Number of ways to clear hormones from the blood - Lipid soluble hormones will stay in blood a lot longer, physically bound to proteins, not easily metabolized o Those that are bound to plasma protein, do not contribute to the free concentration of hormone - Example: o Steroid hormones half-life is 20-100 minutes o Thyroid hormones: plasma bound for 1-6 days o By being bound to plasma protein, prevents them from being inactivated by enzymes - (Not bound to plasma protein) Amine has half life of 10 sec, Insulin half life of 10 minutes, will be taken up or degraded quickly in the blood Recap: Regulation of concentration of hormones is due to: - Rate of secretion by the glands (major) - Rate of metabolic clearance o Inactivation and excretion of hormone o Hormones bound to plasma proteins does not contribute to free hormone concentration o Extent of binding to plasma proteins – for lipophilic hormones o Rate of metabolic activation – for a few hormones Clicker Q Which class of hormones is derived from cholesterol? - Steroid