Download Neuroendocrinology: Regulation of Physiological Processes

PHPY5085Q–Neuroendocrinology:RegulationofPhysiologicalProcesses
Spring2016:TBA
Tuesdays&Thursdays,4:30PMto6:30PM
Syllabus:
Lecture1:IntroductiontoNeuroendocrinology:HypothalamusandPituitary
Anatomyofthehypothalamus,pituitaryandmedianeminence
Hypophysiotrophichormones
TRH,CRH,GnRH,GHRH,Somatostatin,Dopamine,PACAP
Melanocortins
PosteriorPituitary
Oxytocin,Vasopressin
Feedbackloops
Negativefeedback(engineeringanalogy)
Positivefeedback(oxytocin)
HomeostaticFeedback
3‐tiered(basicsincethesewillbecoveredlaterinclass;HPT,
HPA,HPG)
2‐tiered(moredetailhere;Prolactin,GH)
ReflexiveFeedback
Fixed:oxytocin
Graded:Vasopressin
Characteristicsofbloodbrainbarrier(paperbyMulleretal;2010illustrating
structuraldifferencesatthelevelofthemedianeminenceandthird
ventricle)
DiseasesofPituitaryregulation
Lecture2:HypothalamicPituitaryThyroid(HPT)Axis
Thyroidgland
Grossanatomy
Folliclecell
Thyroidhormone(TH):synthesis,release,metabolism(deiodonase)
THreceptors:genomicandnon‐genomicsignaling
THcellularandsystemiceffects
Thyrotropinreleasinghormone(TRH):location,secretion,metabolism,
receptor
Thyroidstimulatinghormone(TSH):structure,receptor,cellulareffects
Somatostatin
Negativefeedback:Ultrashort,short,long
TRHlikepeptides
NeuralregulationofnegativefeedbacktoTRH
Brainstemcatecholamineneurons(cold)
Hypothalamicarcuatenucleus
Hypothalamicdorsomedialnucleus
EffectsoffastingandleptinonHPTaxis
Lecture3:HypothalamicPituitaryAdrenal(HPAaxis)
Introduction AdrenalGland
StressResponse
Stressneurocircuitry
Adrenalhormones
Mineralocorticoids,Aldosterone
Glucocorticoids
Systemicaction
Receptors
CorticotropinReleasingHormone(CRH)
BrainCRHsystem,receptors
Urocortins
CRHbindingprotein
Adrenocorticotropichormone(ACTH):derivationfromPro‐
opiomelanocortingene,receptor,signaling
Feedback
Glucocorticoids
Vasopressin
AfferentneuralregulationofthePVNCRHneurons
Adrenalectomy
ChronicStress
Desensitizationandhabituation
Metabolicsyndrome
Lecture4:HypothalamicPituitaryGonadal(HPG)axis
Male
HPGaxis
Testosteroneeffects
Signaltransduction:Lutenizinghormone(LH),Folliclestimulating
hormone(FSH),testosterone
Commonfeatures:maleandfemaleHPG
Whymalesdonotcycle
Female
Reproductivecycledefinition
FemaleHPGaxis
Menstrualcycle:tissueevents
Menstrualcycle:hormonalevents
Estrogeneffects,receptorsignaling
Reproductivecentersofthebrain
Hypothalamus:anterior/preopticarea,ventrobasalinput,nucleus
sagitalis
Sexualdimorphism(male/female;homosexualmale)
MechanismsunderlyingtheLHsurge
HowthegonadotropeselectivelycontrolsFSHvsLHsecretion
Inhibin,activin,follistatin
GnRHpulses
PACAP
Gonadotropininhibitoryhormone
ShiftinestrogenfromnegativetopositivefeedbackduringtheLH
surge
GnRHpulsatility,receptorsignaling
SexhormonefeedbacktoGnRH
Astrocyticprogesterone
Interactionbetweenestrogenandneuroprogesterone
Arcuatekisspeptinneurons
Differentialfeedbackmodel
Energyhomeostasis
Kisspeptinneuronsandleptin
Orexins
Steroidogenicfactor‐1(SF‐1)
Lecture5:Theneuroendocrineregulationofenergybalance
Historicallesioningstudies
Neuroanatomy
Hypothalamicregulationofthesympatheticnervoussystem
Glucosehomeostasis(liver,pancreas)
Hypoglycemiaandcounterregulation
Freefattyacids
Regulationofenergybalance
Neuropeptides
Arcuatenucleus(neuropeptideY,melanocortins)
Lateralhypothalamus(orexin,melaninconcentrating hormone)
Ventromedialnucleus(brainderivedneurotrophicfactor,
PACAP,SF‐1)
Paraventricularnucleus(CRH,TRH,oxytocin,galanin)
Feedbacksignals
Satietyhormones(insulin,leptin)
Nutrientsignals(glucose,fattyacids,aminoacids)
Glucoseandfattyacidsensingneurons
Integrationofnutrientsignals
Nutrientrelatedsignals(gutpeptides)
Satiety(cholecystokinin,glucagon‐likepeptide,peptide
YY,apolipoprotein,enterostatin,bombesin‐family,
amylin)
Orexogenic:ghrelin
Feedbackloops
Rewardpathway
Fastingandobesity/Diabetes
Lecture6:Neuroendocrineregulationofbiologicalrhythms
Biologicalrhythmsdefined
Ultradian,circadian(focus),infradian
Circadianrhythmofmetabolicenzymesasexamples
Pacemakers
Suprachiasmaticnucleus(SCN)
Clockgenes
Mechanismsoflightentrainment
Melatoninandpinealgland
SCNregulationofthepineal(sympatheticinnervations)
Melatoninreceptorsandphysiologicalfunctions
Seasonaleffects
Metabolicregulationofclockgenes
Otherentrainers(mealpattern,activity,bodytemperature)
GlucocorticoidsstabilizetheSCN
Circadiandisruption
Jetlag
Metabolicdisease
Cancer
Lecture7:NeuroendocrineImmunology
Overviewoftheimmunesystem
Functionsoftheimmunesystem:
1.Attackforeignorganismordiseasedcells
2.Provideenergyforthesetasks
Immunesystemandthebrain
Interactionsbetweentheimmunesystemandotherneuroendocrinesystems
Relationshipbetweentheimmunesystemandenergybalance
“Howtheimmunesystemsusestheneuroendocrinesystemtofeedit”
Circadianregulationoftheimmunesystem
Illnessinducedanorexia‐cachexiavsstarvation
Metabolicdiseaseandinflammation