Review #3 40 Fill class evaluation forms on-line Course overview and web review Preview of test #3 and a student e-mail note This course instructor is JP Advis DVM, PhD. Other courses thought by this instructor are: System Physiology and Endocrinology in Summer, Endocrinology and Integrative Physiologygy + Lab in Fall, and Animal Reproduction and Pathophysiology in Spring. Course main “punch line” “story line” 1 Basis of Endocrine Physiology levels of organization Basis of Endocrine Physiology structure - function The classical hormones fall into 3 categories: 1- derivatives of the aminoacid tyrosine 2- steroids, which are derived from cholesterol 3- peptides/proteins, which comprise the largest and most diverse class of hormones. 2 Basis of Endocrine Physiology homeostatic regulation Basis of Endocrine Physiology integrator center homeostatic regulation afferent “story line” S sensor E diagram for a control system as that present in a refrigerator S a “reflex arc” a base for a control model negative feedback “story line” efferent “story line” E effector … if story lines are linked through an integrator, then you have “control”… 3 Specific tips for this course • Probably the single most important tip for this course is to prepare ten sentences with what you consider are the main “punch lines” for each lecture. You should rank your sentences in what you consider is a list from most to less important ideas presented in each lecture. You should also edit your sentences, for example, check if more than one sentence might be combined into a better sentence. Make sure your sentences cover the whole of the topic presented in the lecture. • Use this list to discuss it with fellow students and with your instructor. • Please be aware that in order to write a single, concise and informative sentence you need to understand, rather than memorize, a piece of information. To test yourself on how good you are doing, check if your sentence used your own words or if you just borrowed part of a sentence you read in your textbook. Consider that if you can not write an idea into a single sentence, you probably have not yet understood the material. Websites “punch lines” ideas 1.- Some basic endocrine concepts and the methodologies used to study a) definition of hormone and of endocrine, neurocrine, paracrine transmission b) methodologies used in endocrinology (RIAs, RRA, ICC, hybridization, …) c) how liposoluble and watersoluble hormones are made in general (SER vs RER) d) hormone story line as a “trick” to think of steps involved in hormone function 2.- A “story line” table for all hormones. Things to look up in the table a) hormones that are water soluble and those that are lipo soluble b) hormones involved in hierarchies (gonadal, adrenal, thyroid, …) c) hormones involved in metabolism (glucose, calcium, sodium, water, …) d) inputs to endocrine glands and hormone effects on different organs 3.- “Reflex-arc” like-models and the “- Fb” for different hormones a) inputs, integrators, -Fb in the control of different hormones (the refrigerator) b) role of the hypothalamus in neuroendocrine control of the endocrine system c) theoretical components of a control system, homeostasis and rheostasis d) endocrine and neuroendocrine control and their disruption in pathology 4 Websites “punch lines” ideas 4.- Some basic points on mechanism of action of liposoluble hormones a) intracellular receptors mainly … but also membrane receptors (experiments) b) effect on protein synthesis mainly, … but some also have membrane receptors c) cys and trans elements involved in regulation at the promoter level .. integrator d) permissive effects of some liposoluble hormones (e.g. T3-4, Cortisol, E2,…) 5.- Some basic points on mechanism of action of water soluble hormones a) plasma membrane receptors … but they also have access to the genome b) an ultimate effect on channels and enzymes underlies endocrine action c) GPCR and Tyr-kinase links, different paths to protein phosphorylation d) Permissive effects of some watersoluble hormones (e.g. Prl on LH receptors) 6.- Some basic points on the hypothalamic pituitary “connection” a) hypothalamic anterior pituitary portal system (neurohormones, amplification) b) hypothalamic posterior pituitary system (a good example of neuronal events) c) the pituitary receives 2/3 of the outputs from PVN (a main brain integrator) d) the median eminence as a final brain integrator site for endocrine function Websites “punch lines” ideas 7.- Some basic points on anterior pituitary (AP) hormones a) most AP hormones are tropic / trophic hormones that act on other endocrine glands b) all AP hormones are controlled by hypothalamic hypophysiotropic neurohormones c) the hypothalamic – AP unit acts as an integrator and amplification control unit d) the hypothalamic – AP link is a vascular one since both tissues have different origin 8.- Some basic points on posterior pituitary (PP) and pineal hormones a) PP hormones are neurohormones made in the hypothalamus and released in the PP b) the hypothalamus and PP have the same embryological origin (as opposed to AP) c) PP hormones are involved in water metabolism and myoepithelial contraction d) AVP is also released in ME and acts in AP as a CRH, albeit by different mechanism 9.- AVP, OT, and melatonin a) AP hormones (ACTH, GH, PRL, TSH, LH, FSH, MSH, ßEND) b) PP hormones (AVP, OT) c) Pineal hormone (Melatonin) (*) (*) (*) (*) Expand story line for each of these hormones 5 From the course website 10.- Calcium hormones a) PTH b) vitD c) calcitonin 11.- Thyroid hormones a) T3-T4 b) TSH c) TRH 12.- Catecholamines a) Cas and the ANS b) Epi c) Nepi / DA (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others S E From the course website 13.- GI hormones a) Gastrin b) Secretin c) GLP-1 14.- Pancreas hormones a) Insulin b) Glucagon c) Vit. D 15.- Steroid hormones a) Mineralocoticoids (Aldosterone b) Glucocorticoids (Cortisol) c) Gonadal steroids (E2, P4, T) (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others S E 6 From the course website 16.- Glucocorticoids a) Cortisol b) ACTH c) CRH 17.- Growth hormones a) GH b) IGFs c) GHRH, SS 18.- Mineralocorticoids a) Aldosterone b) Renin c) Ag II (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others S E From the course website The start 19.- Integration overview a) Redundancy b) Reinforcement c) Push-pull d) Modulation & The end 20.- Complete table 21.- Complete feedbacks 22.- Complete summaries The story line and the feedback concepts are the ABC of endocrinology. This is the minimum you absolutely need to know. The integration paradigms presented in the final lectures are an attempt to provide examples of “real life” examples were multiple endocrine systems interact. S E 7 From the course website 23.- Sex development a) Story lines b) Feedbacks c) Puberty 24.- Menstrual cycle a) Story lines b) Feedbacks c) Menstrual cycle Basic concepts from these lectures were used in the last two lectures (biological clocks and aging). S E From the course website 25.- Food intake a) Story lines b) Feedbacks c) Food intake 26.- Immunology a) Story lines b) Feedbacks c) Stress response Basic concepts from these lectures were used to reinforce the “balance” idea behind integration. S E Pro-inflamatory response Th1 / Th2 Anti-inflamatory response 8 From the course website gonadal hierarchy 27.- Biological Rhytms a) Story lines b) Feedbacks c) Clocks & entrainment E2 P4 receptor 28.- Reproductive Aging a) Story lines b) Feedbacks c) Menopause S CS E GnRH Young AP Basic concepts from these lectures were used to show how homeostatic control systems my fail with age (“timing failure”). Middle - Aged gonad S E E2 / P4 From the course website Overview of the course based on some essay questions, or which would be the questions of your final exam if such exam was an essay test. The basic elements presented in this course were summarized in 3 main thrusts: a) story lines for each hormone involved in communication issues; b) feedback systems used to regulate the multiple hormone functions; and c) mechanisms of action by which enzymes / channels respond to hormones Having these elements in mind attempt to organize and to answer the questions described below (each question deals with an issue used in the final section of the course to review and to integrate all material covered in this course). 9 From the course website Control of food intake. The neuroendocrine control of food intake involves neurotransmitters and neuropeptides as inputs and outputs to an integrator located in the PVN. From a conceptual view of nerve cell connectivity and function, describe a possible circuitry consisting of neuronal and endocrine signals (to and from the PVN integrator) operating during the two opposite metabolic conditions of feeding / satiety (hypermetabolic condition) and fasting / starvation (hypometabolic condition). From the course website The menstrual cycle. Gonadotropin release is thought to be controlled by an hypothalamic network of LHRH or GnRH neurons, delivering its hypophysiotropic peptide to primary portal vessels at the median eminence, which regulate gonadotropinproducing cells in the anterior pituitary. From a conceptual view of nerve cell connectivity and function, describe a mechanism that would allow an hypothalamic network of LHRH or GnRH neurons (or two subnetworks, e.g. tonic vs phasic) to synchronize both its tonic (or basal pulsatile gonadotropin release) and its phasic (or preovulatory surge-like release of gonadotropin) operation, as it is observed during the menstrual cycle. In addition, consider how the pulsatile output of such hypothalamic network might affect the anterior pituitary release of gonadotropins. 10 From the course website The stress response. The response to stress involves neurotransmitters and neuropeptides as inputs and outputs to an integrator located in the PVN. From a conceptual view of nerve cell connectivity and function, describe a possible circuitry consisting of neuronal and endocrine signals (to and from the PVN integrator) operating during the stress response. From the course website An example of integration at the CNS level. An anovulatory syndrome is associated with endocrine events involving the interface between stress and reproduction, as for example in ballet dancers, marathon runners, aging and psychological stress. Provide an explanation for one of such anovulatory events based on the three basic elements presented in this course. 11 From the course website Another example of integration at the CNS level. How do you envision that rhythm–related signals may play a role in the neuroendocrine control of reproduction and / or food intake (you may select only one or compare both). Consider a potential role involving SCN and entrainment signals as well as hypothalamic and non-hypothalamic neuroendocrine pathways participating in their control circuitry. A student e-mail after test 2 Hi, Today after I had handed in my exam, I noticed something that really frustrated me and another student, who was walking out at about the same time as me. There was a student who had a pile of notes on the ground and was paging through them looking for answers for the exam. I don’t want to be considered as someone to rat one out, but I studied a lot for this exam and I am sure everyone would have liked to have their notes with them. Sorry but this got me really upset and just wanted to touch base with you on the matter. 12
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