Slide 1Types of inputThe 4th path to target response: neuroendocrineSlide 4The pituitary is really two glandsAnterior & posterior pituitaries do NOT share circulationThe posterior pituitaryThe anterior pituitaryHPA allows endocrine system to respond to complex stimuliHormones of the hypothalamic anterior pituitary axisSlide 11Anterior pituitary control loopsHPA feedback is key to endocrine diseasePrimary vs secondary endocrine disease in the HPANote thatRemember this?You now know EVERYTHING about themReview questionsNotesNotes (cont.)PGY452/552: Endocrine physiology4. Complex inputs and the central nervous systemA. CNS—endocrine anatomy B. Posterior pituitaryC. Anterior pituitary1. Hypothalamic inputs2. Hormones3. FeedbackD. Endocrine diseaseE. You now know everything!Types of inputSimple inputs Sensed by endocrine tissue directlyResponse regulates inputAlways negative feedbackExamples[Ca²⁺]ECFGlucoseComplexCNS integrated regulation of complex stimuliFeedback can be NegativePositive2HHHHHHHHHHHSimpleInputSimpleInputResponseHormoneThe 4th path to target response: neuroendocrineSpecialized nerve cellsMany peptide hormones are neurotransmittersCan go both ways3HResponseHHHsignalHMost neuronal control occurs through the hypothalamus and the pituitary gland4PinealglandPituitary glandDiencephalonDiencephalonThalamusHypothalamusCorpus callosumThe pituitary is really two glands5Anterior: frontPosterior: backHypothalamusInfindibulumSphenoid bonePosterior pituitaryan extension of hypo-thalamic neural tissuePosterior pituitaryan extension of hypo-thalamic neural tissueAnterior pituitarya true gland of epithelial originAnterior pituitarya true gland of epithelial originAnterior pituitary + hypothalamus = Hypothalamic-pituitary axis (HPA)Anterior pituitary + hypothalamus = Hypothalamic-pituitary axis (HPA)Anterior & posterior pituitaries do NOT share circulation6Do not interact directlyDo not interact directlyThe posterior pituitary7Hypothalamus: Prohormones made in large neural somaHypothalamus: Prohormones made in large neural somaProhormones travel down long axonsProcessed to mature hormonesProhormones travel down long axonsProcessed to mature hormonesReleased into capillary bedsReleased into capillary bedsTo general circulationTo general circulationBlood flow inTwo 9 amino acid peptide hormones:•Antidiuretic hormone (ADH; Vasopressin)•OxytocinTwo 9 amino acid peptide hormones:•Antidiuretic hormone (ADH; Vasopressin)•Oxytocin8Hypothalamic regulating hormones made in “small” neural soma*Hypothalamic regulating hormones made in “small” neural soma*Regulating hormones released into portal circulationRegulating hormones released into portal circulationTravel down capillary bedsTravel down capillary bedsTrophic hormones to general circulationTrophic hormones to general circulationBlood flow inRegulate trophic hormone synthesis and release from specific endocrine epithelial cellsRegulate trophic hormone synthesis and release from specific endocrine epithelial cells*Small compared to posterior pituitary neurons*Small compared to posterior pituitary neuronsThe anterior pituitaryHypothalamic integrating centerHypothalamic integrating centerComplex inputsSix hypothalamic regulatory hormonesSix anterior pituitary tropic hormonesHPA allows endocrine system to respond to complex stimuli9EmotionsEmotionsPainPainSensesSensesSleep/wakeSleep/wakeWater balanceWater balanceTemperatureTemperatureEnergy in & outEnergy in & outRegulate•Metabolism•Stress response•DevelopmentAutonomic inputsAutonomic inputsHormones of the hypothalamic anterior pituitary axis10HypothalamusPIH(dopamine)PIH(dopamine)TRHTRHCRHCRHGHRHGHRHGnRHGnRHProlactinTSHACTHGHFSH LHMany tissuesMany tissuesAnterior PituitaryGonadsGonadsAndrogens & estrogensAndrogens & estrogensAdrenal cortexAdrenal cortexCortisolAldosteroneCortisolAldosteroneThyroid glandThyroid glandThyroid hormoneThyroid hormoneBreastBreastSomatostatin(GHIH)Somatostatin(GHIH)IGF-1IGF-1Anterior pituitary secretes hormones from specialized cell types11Growth hormoneThyroid Stimulating HLuteinizing HFollicle Stimulating HAdrenocorticotropinProlactinSomatotrophThyrotrophGonadotrophCorticotrophMammotrophProportion of each cell type:This is where the idea of a master gland comes fromAnterior pituitary control loopsAll hormones regulated by feedbackTHIS TERMINOLOGY APPLIES ONLY TO THE HPAAlsoLong and short loop positive feedbackUltrashort loops within the anterior pituitary or hypothalamusShort/long loop negative feedback the most commonHOMEOSTASIS!12Anterior pituitaryPeripheral endocrine tissueInputInputTHHRHHypothalamusLong loop negative feedbackShort loop negative feedbackH: hormoneT: tropicR: releasingUltra short loop negative feedbackHPA feedback is key to endocrine diseaseReceptor/Tissue fails to respondHormone deficiency – hyposecretionDestruction of the glandInfectionInfarctionAutoimmune attackGenetic defects in hormone productionProtein hormone gene mutationMutations in any protein involved in steroid or protein hormone synthesisExcess hormone – hypersecretion Tumors → not subject to feedback or other regulationGlandEctopic due to dedifferentiation of non-endocrine tissueAbuse -- Overconsumption of prescribed or abused HormoneHormone receptor agonist13Primary vs secondary endocrine disease in the HPA14Anterior pituitaryPeripheral endocrine tissueTHHRHHypothalamusAnterior pituitaryPeripheral endocrine tissueTHHRHHypothalamusTumorPrimary disease↑H/↓TH/↓RHTumorSecondary disease↑H/↑TH/↓RHExcess peripheral hormone causes the symptomsExcess peripheral hormone causes the symptomsNote that“Releasing hormones” or “inhibiting hormones” are always secreted by the hypothalamusReleasing hormones: mostly GαqInhibiting hormones: GαiGHRH vs GHIH: Gαs vs GαiAnterior pituitary hormones are usually given some sort of regulatory designationThyroxine stimulating hormoneAdrenocorticotrophic hormoneFollicle stimulating hormoneHypothalamus all peptides except dopamine (PIH)Anterior pituitary all glycoproteins & peptidesNo steroid hormones are made in the hypothalamus or pituitary15Remember this?16We will cover ~40 hormones100’s meet the technical definition100’s meet the technical definition>70 recognized hormones>70 recognized hormonesYou now know EVERYTHING about them17Don’t