Ingestive Behaviors 21. Introduction. Page 1. control and story lines. (a review of general endocrinology) Integration (or the basic reflex arc model)
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1 Ingestive Behaviors 21 (a review of general endocrinology) A neuroendocrine system: components, a reflex arc, the endocrine system, the AN, endocrine / nervous systems as afferents and efferents, the theoretical comparator or integrator unit, membrane potential, transcription factors and integrators, crosstalk at a subcellular level as regulatory paradigm lements involved in the neuroendocrine of food intake, the hypothalamic PVN, M and POA as integration centers, discussion of other integrated neuroendocrine systems (stress and temperature regulation linked to stress and food intake) and of obesity and as a story of circles, intersecting circles, intersecting circles, intersecting... Introduction afferent story line sensor and story lines Integration (or the basic reflex arc model) integrator center negative feedback story line basic diagram for a system as that present in a refrigerator efferent story line effector Page 1
2 Physiological ndocrinology Circles within circles nergy production, utilization and storage Maintenance of internal environment Growth and development Reproduction The endocrine system is a communication system involved in homeostatic of life. It acts through its hormones which four main basic processes A basic reflex arc model has organization levels, structure / function, Physiological ndocrinology Circles within circles The basic reflex arc model is based on the neuronal components of a reflex arc Page 2
3 Theoretical elements Circles within circles variable under (t C / F) thermostat (set point) t C / F detector (feedback) comparator common language error signal (on/off) engine (amplifier) hypothalamus set point long loop negative feedback N T C A P short and ultrashort negative feedbacks hierarchies: gonadal TARGT adrenal thyroid others FINAL NDOCRIN FFCT Refrigerators are regulated with similar components to that of an endocrine sytem Negative feedback is gonadal hierarchy C adrenal hierarchy C thyroid hierarchy C 2 P4 receptor comp. Cortisol. receptor comp. T3 receptor comp. Circles within circles N TC GnRH AP CRH AP TRH AP gonad adrenal thyroid 2 / P4 cortisol T3 - T4 The basic reflex arc model is shown by the various endocrine hierarchies Page 3
4 Negative feedback is Recovery of the HPA axis after Cushing syndrome or chronic dexamethasone As a rule, brain elements of a feedback regulation are usually the most important Negative feedback is PTH and Vit.D increase blood Ca while Calcitonin decreases it blood Ca decrease calcium receptor parathyroid gland PTH PTH receptor Gs / AC Gq / PLC Vit. D PTH absorption resorption blood intestine Ca bone secretion formation Calcitonin Calcitonin reabsorption filtration PTH kidney bone formation, osteoblast kidney, Ca filtration intestine, Ca secretion bone resorption, osteoclast kidney, Ca reabsorption, Vit. D intestine, Ca absorption Calcitonin receptor Gs / AC Calcitonin thyroid gland calcium receptor blood Ca increas e An exception to the rule stated in the previous slide is that of Ca homeostasis Page 4
5 Negative feedback is HPA axis is involved only under disease conditions A partial exception to the rule stated in the previous slides is RA-aldosterone system Neural systems Neuronal elements in the communication operation within a system Page 5
6 Neural systems The action potential as the neuronal communication unit ndocrine systems The hormone as the endocrine communication unit Page 6
7 AN P pre post Ach Ne Integrator () negative feedback afferent / efferent communication pathways might be neurogenic and / or endocrine pathways Feedback signals are effector signals which are recognized as inputs How an integrator might work A background for a neurogenic integrator comes from the function of PP and IPP Page 7
8 How an integrator might work A background for both neurogenic and endocrine integrators comes from camp How an integrator might work R Na / K pump camp ----> PKA ----> channel / enzyme AC Protein synthesis teroid + R ----> R 5 3 HR XX1 1 mrna R DNA additional transcription factor A background for both neurogenic and endocrine integrators comes from steroids Page 8
9 How an integrator might work A background for neurogenic / endocrine integrators comes from AgII and cross-talk How an integrator might work PVN POA M The PVN, the M and the POA are the three main CN integrators discussed in lectures Page 9
10 Hypothalamic hypometabolism PVN M POA T3-T4 (low) TH (low / normal) TRH mrna (low) UC proteins (low) TRH-induced TH release (high) TRH release (low) inhibits TH release Insulin (low) Glucagon (high) Cortisol (high) pinephrine (high) LH/FH (low) Leptin (low) Cas, NPY, amh, ARN thermogenesis (low) energy expenditure (low) Tertiary hypometabolic states (hibernation, startvation) show how integrators work The neuroendocrine of food intake also shows how integrators work and fail Page 10
11 PYY Ghrelin Insulin CCK Leptin A recent article in Time magazine targeted for a general audience about this topic Ultimately how you look will result from your integrator s balancing act Page 11
12 Inputs to the central network Glucose availability glucose sensitive neurons in brain stem (NT, AP), hypothalamus (VMH-DMH,PVN) and hepato-portal circulation (to NT). ensory stimuli to NT, PBN and cortex. Body energy stores leptin in ARC- VMH The PVN is a main central integrator involved in neuroendocrine of food intake Long and short term inputs e.g. Leptin inhibits food intake Long - term Insulin, Leptin cortisol, T3-T4, GH / IGF1 hort - term Glucose, Proteins and Fats GI volume and GI peptides The PVN is a main central integrator involved in neuroendocrine of food intake Page 12
13 Leptin and food intake Kg leptin women Men body weight body fat leptin body weight pair-fed leptin fasting % body fat Clinical and experimental data suggesting that leptin plays a metabolic role Leptin and food intake Parabiotic experiment of Coleman lack satiaty factor normal ob/ob ob/ob resistant to satiaty factor db/db db/db e.g. leptin inhibits food intake and stimulates energy expenditure db/db ob/ob db/db ob/ob Leptin is secreted from the adipocytes and signals the brain about their status Page 13
14 Leptin and food intake e.g. leptin inhibits food intake and stimulates energy expenditure Leptin acts centrally (e.g. HPG, HPT, HPA) & peripherally (e.g. immune, angiogenesis) Leptin and food intake e.g. leptin inhibits food intake and stimulates energy expenditure Leptin has a variety of central and peripheral effects, as outlined in this slide Page 14
15 Leptin and food intake Long form of the leptin receptor (Ob-Rb)mediates leptin actions Koletsky rats having a point mutation (Ob-Rb) are obese ----> BBB e.g. leptin inhibits food intake and stimulates energy expenditure CN receptors for leptin are located in the AR/M (3V) and in the area postrema (4V) Leptin and food intake e.g. leptin inhibits food intake and stimulates energy expenditure Leptin receptors in AR/M are located in NPY/AGRP & POMC/CART containing cells Page 15
16 Leptin and food intake leptin inhibits food intake & stimulates energy expenditure BB stimulate inhibit Neuronal = N Blood - Born = BB DMH PVN POMC, amh, CART, CRH NPY, AGRP, MCH, Orexin BB PBN AP LH DMN BB VMH A ARC M NT CN receptors for leptin are located in the AR/M (3V) and in the area postrema (4V) N Leptin and food intake leptin inhibits food intake & stimulates energy expenditure stimulate POMC, amh, CART, CRH inhibit NPY, AGRP, MCH, Orexin Catecholamines Na + (NT-PVN) ; DA - (LH-PVN) erotonin 5HT1b - (LH-PVN) Histamine GABA H2 - (VMH-PVN) GABAa + (VMH) and - (LH) NPY and Galanin NPY + ; GAL + (ARC-PVN) CRH and CCK CRH - (A-VMH) ; CCK - (NT-PVN) amh, AGRP and GLP1 amh - ; AGRP + (ARC-PVN-MC4R) GLP1 - (NT-PVN) Orexins and MCH Orexin + ; MCH + (LH-PVN) CART CART - (ARC-DMH, NT) Main central pathways regulating food intake Page 16
17 Leptin and food intake Main central pathways regulating the effect of leptin on food intake Integrator s balancing act Obesity & are only the extremes of the central integrators playfield Page 17
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