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HypothalamusHypothalamus -- pituitarypituitary -- adrenaladrenal glandsglands Magdalena Gibas-Dorna MD, PhD Dept. of Physiology University of Medical Sciences Poznań, Poland Hypothalamus - general director of the hormone system. At every moment, the hypothalamus analyses messages coming from: the brain and different regions of the body. Homeostatic functions of hypothalamus include maintaining a stable body temperature, controlling food intake, controlling blood pressure, ensuring a fluid balance, and even proper sleep patterns. Cell bodies of neurons that produce releasing/inhibiting hormones Hypothalamus HypothalamusHypothalamus releases Arterial flow Primary capillaries in median eminence hormones at Long Releasing Portal hormones Anterior veins median eminence pituitary hormone Releasing/ inhibiting hormones and sends to anterior pituitary ANTERIOR PITUITARY via portalportal veinvein. Secretory cells that produce anterior pituitary hormones Anterior pituitary hormones Venous outflow Gonadotropic Thyroid- Proactin hormones stimulating ACTH Growth (FSH and LH) hormone hormone ControlControl ofof pituitarypituitary hormonehormone secretionsecretion byby hypothalamushypothalamus • Secretion by the anterioranterior pituitarypituitary is controlled by hormones called hypothalamic releasing hormones and inhibitory hormones conducted to the anterior pituitary through hypothalamichypothalamic -- hypophysialhypophysial portalportal vesselsvessels .. • PosteriorPosterior pituitarypituitary secrets two hormones, which are synthesized within cell bodies of supraoptic and paraventricular nuclei of the hypothalamus and transmitted throughthrough axonsaxons of these neurons. FunctionFunction ofof thethe releasingreleasing andand inhibitoryinhibitory hypothalamichypothalamic hormoneshormones • Thyrotropin- releasing hormone (TRH)(TRH) - causes release of thyroid - stimulating hormone (TSH) • Corticotropin - releasing hormone (CRH)(CRH) – causes release of ACTH • Growth hormone releasing hormone (GHRH)(GHRH) - causes release of growth hormone, and • Growth hormone inhibitory hormone (GHIH)(GHIH),, which is the same as the hormone somatostatinsomatostatin and which inhibits the release of growth hormone. FunctionFunction ofof thethe releasingreleasing andand inhibitoryinhibitory hypothalamichypothalamic hormoneshormones • Gonadotropin - releasing hormone (GnRH)(GnRH) – causes release of the two gonadotropic hormones, LH and FSH • Prolactin inhibitory hormone (PIH)(PIH),, - belived to be dopamine - causes inhibition of prolactin release. • PRL-releasing factor (PRF)(PRF).. - belived to be TRH – increases prolactin release TheThe locationlocation ofof pituitarypituitary (hypophysis)(hypophysis) relativerelative toto brainbrain andand hypohalamushypohalamus Hypothalamic-PituitaryHypothalamic-Pituitary SystemsSystems Hypothalamus The pituitary is controlled largely by the hypothalamus and regulates numerous processes. Anterior = endocrine, 6 hormones Pituitary stalk Intermediate = minor, 1 Optic chiasm Posterior lobe Posterior = neuroendocrine, 2 Anterior Intermediate lobe lobe Pituitary gland SixSix veryvery importantimportant hormoneshormones areare secretedsecreted byby anterioranterior pituitarypituitary : • Secreted by lactotropes prolactin (PRL)(PRL) • Secreted by thyrotropes thyroid stimulating hormone (TSH)(TSH) • Secreted by gonadotropes follicle - stimulating hormone FSHFSH, and luteinizing hormone LHLH • Secreted by corticotropes adrenocorticotropin (ACTH)(ACTH) • Secreted by somatotropes growth hormone (GH;(GH; somatotropin)somatotropin) HypopituitarismHypopituitarism • deficiency of one or more anterior pituitary hormones, which results in insufficient stimulation and therefore insufficient hormonal output of the respective target glands • Tumors • Pituitary irradiation • Pituitary apoplexy • Postpartum pituitary necrosis (Sheehan’s syndrome due to postpartum hemorrhage and hypovolemia) How can pituitary tumors cause hypopituitarism? e.g. what is the effect of prolactinoma on fertility in both sexes? Paraventricular nucleus (oxytocin) Supraoptic nucleus (ADH) Hypothalamus PosteriorPosterior pituitarypituitary receives axons from the supraoptic ( ADH) and paraventricular Posterior pituitary nuclei ( oxytocin). To venous circulation Arterial blood supply Two hormones are secreted by posteriorposterior pituitarypituitary:: • AntidiureticAntidiuretic hormonehormone (ADH;(ADH; vasopressin)vasopressin) • OxytocinOxytocin • IntermediateIntermediate -- lobelobe cells secretes: • POMCPOMC (proopiomelanocortin), which is precursor of alpha- MSH (melanotropin ) GrowthGrowth hormonehormone (somatotropin)(somatotropin) Stress centers Chemical In the brain stimuli Sleep center In the brain Hypothalamus Portal • GHRH, somatostatin (GHIH) vein and ghrelin control GH release GHRH Somatostatin (+) ( - ) (+) • pancreatic somatostatin has Ghrelin from Somatotrophs of stomach (+) Anterior pituitary other functions (inhibits hormone (-) secretion by and cells) Growth hormone Liver Somatomedins StimuliStimuli thatthat increaseincrease secretionsecretion ofof GH:GH: • GHRH; Ghrelin (brain-gut • Increase in circulating levels peptide) of certain amino acids • Deficiency of energy • Glucagon substrate: - Hypoglycemia • Stressful stimuli - Exercise • NREM stage of sleep - Fasting GHGH isis releasedreleased inin pulses,pulses, withwith aa majormajor peakpeak duringduring deepdeep sleepsleep beforebefore REREMM Sleep Plasma GH concentration (relative units) Noon 6 PM Midnight 6 AM Time of day GhrelinGhrelin • Produced mainly by stomach (released into blood) • Other sources: intestines; hypothalamus • Receptors located in pituitary (GH), hypothalamus (food intake), heart, blood vessels ( BP) GhrelinGhrelin causescauses :: GH release food intake (appetite- stimulatory peptide) via NPY neurones in hypothalamus fat utilization (GH- inependent mechanism) glucose utilization StimuliStimuli thatthat decreasedecrease secretionsecretion ofof GH:GH: • REM sleep • FFA ( of ghrelin release) • High blood glucose • Growth hormone concentration ( of ghrelin release) • Somatomedins • Cortisol PhysiologyPhysiology ofof growthgrowth GHGH stimulatesstimulates cartilagecartilage andand bonebone growthgrowth by:by: • increased depositiondeposition ofof proteinprotein by the chondrocytic and osteogenic cells that cause bone growth • increased rate of reproductionreproduction of these cells • the specific effect of convertingconverting chondrocyteschondrocytes intointo osteogenicosteogenic cellscells, thus causing specific deposition of new bone. DirectDirect andand indirectindirect effectseffects ofof GHGH • Direct effects are the result of growth hormone binding its receptor on target cells • Indirect effects are mediated primarily by an insulin-likeinsulin-like growthgrowth factor-1factor-1 andand 22 (IGF-1(IGF-1;; IGF-2IGF-2),), hormones that are secreted from the liver and other tissues in response to GH SomatomedinsSomatomedins -- thethe polypeptidepolypeptide growthgrowth factorsfactors secretedsecreted byby thethe liverliver (IGF-I,(IGF-I, IGF-II)IGF-II) • IGF-IIGF-I (insulin-like growth factor) stimulates skeletal growth by increasing collagen and protein synthesis in chondrocytes. IGF-I may be also produced locally • IGF-IIIGF-II stimulates tissue growth and increases organ size especially during fetal development (by increasing the rate of: protein synthesis, RNA synthesis, DNA synthesis) DistinguishDistinguish between:between: • Somatotropin - GH • Somatostatin - GHIH • Somatomedin – polypeptide growth factor PhysiologyPhysiology ofof growthgrowth GrowthGrowth isis affectedaffected by:by: • thyroid hormones • androgens sex hormones • estrogens • glucocorticoids • insulin • genetic factors • adequate nutrition PhysiologyPhysiology ofof growthgrowth –– growthgrowth periods:periods: • In humans, there are 2 periods of rapid growth, the first in infancy and the second in late puberty just before growth stops • The first period is a continuation of the fetal growth period • The second growth spurt is due to an interaction between sexsex steroids,steroids, GH,GH, andand IGF-1IGF-1 sexsex hormoneshormones amplitudeamplitude ofof thethe spikesspikes ofof GHGH secretionsecretion IGF-1IGF-1 growthgrowth TwoTwo growthgrowth periodsperiods Although androgens and estrogens initially stimulate growth, they finally terminate growth by causing the epiphyses to fuse to the long bones. 1. Why pituitary dwarfs treated with testosterone first grow few inches and then stop? 2. Why people who were castrated before puberty tend to be tall? PhysiologyPhysiology ofof growthgrowth –– rolerole ofof thyroidthyroid hormoneshormones: • Thyroid hormones have a permissivepermissive actionaction toto GHGH, possibly via potentiation of the actions of somatomedins. • They also appear to be necessary for a completely normal rate of GH secretion • Thyroid hormones have effects on the ossification of cartilage, the growth of teeth, the contorous of the face, and the proportions of the body Long bones continue to grow and elongate (lengthen) through adolescence. This process is called ossification Developing heart that appears as a red nodule While still in the embryonic stage, a baby's heart develops under the supervision of the growthgrowth hormonehormone Adult heart MetabolicMetabolic effectseffects ofof GHGH GHGH playsplays rolerole inin promotingpromoting proteinprotein depositiondeposition • GH directly enhances transport of most amino acids through the cell membranes to the cytoplasm
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  • Tonic Activity in Lateral Habenula Neurons Promotes Disengagement from Reward-Seeking Behavior

    Tonic Activity in Lateral Habenula Neurons Promotes Disengagement from Reward-Seeking Behavior

    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.15.426914; this version posted January 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Tonic activity in lateral habenula neurons promotes disengagement from reward-seeking behavior 5 Brianna J. Sleezer1,3, Ryan J. Post1,2,3, David A. Bulkin1,2,3, R. Becket Ebitz4, Vladlena Lee1, Kasey Han1, Melissa R. Warden1,2,5,* 1Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA 2Cornell Neurotech, Cornell University, Ithaca, NY 14853 USA 10 3These authors contributed equally 4Department oF Neuroscience, Université de Montréal, Montréal, QC H3T 1J4, Canada 5Lead Contact *Correspondence: [email protected] 15 Sleezer*, Post*, Bulkin* et al. 1 of 38 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.15.426914; this version posted January 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. SUMMARY Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the 5 lateral habenula (LHb) has been linked to aversion and negative valence, but its role in regulating the balance between reward-seeking and disengaged behavioral states remains unclear.