Calcitriol hormone and its up and down regulation

Description: these slides explain the calcitriol hormone production and regulation. The effects of calcitriol on body and the related disorders. and also explain the up and down regulation of calcitriol hormone.

1. University of Chakwal, Pakistan

2. Department of zoology
PRESENTED BY: HAFSA KHIZAR
REG. NO: 20M-UOC/ZOL-11
BS ZOOLOGY
SESSION 2020-24
SUBJECT: ENDOCRINOLOGY
SUBMITTED TO: DR SYEDA NADIA AHMAD
TOPIC: CALCITRIOL HORMONE AND ITS UP
AND DOWN REGULATION

3. CalcitriolorbioactiveformofvitaminDisasteroidhormone.
Inhumanbodyithelpstoregulatethecalciumandphosphorus
levels.
Andalsohelpinthemineralizationofbones.
CalcitriolistheactiveformofvitaminDproducedfromits
precursorcalcidiolinthekidney.
Itisimplicatedinanumberofphysiologicalandpathological
processes,includingthemetabolicsyndrome,cancer,immune
systemregulation,andcardiovasculardisorders.(Donatiet
al.,2023).
Introduction

4. ItworkthroughVDR(vitaminD
receptors).
Theycontrolawiderangeoftarget
genesand,inturn,severalcellular
processes.
VDRsareexpressedinpracticallyall
humancelltypes.
Theyaffectthetranscriptionof
roughly3%ofhumangenes.
Figure 1.1: Vitamin D receptors VDR
https://www.researchgate.net

5. TheprimarysourceofvitaminDis
thesun'sultravioletBrays,produced
intheepidermallayersandmostlyin
the290–320nmspectralregion.
Sunlight'sUVBraysbioconvert7-
dehydrocholesteroltopre-vitamin
D3.
Whichisthenthermallyisomerized
toproducevitaminDintheskin.
AftertheformationofVDinthe
skinitisreleasedintotheblood
stream(Donatietal.,2023).
Figure 1.2: UV B radiations entering the skin
https://images.squarespace-cdn.com.

6. WiththehelpofVDbindingproteins
itistransportedtoliver.
Ittransformedinto25-hydroxyvitamin
D(calcidiol,25OHD).
Calcidiolisnottheactiveformsoit
movetokidney.
Itismediatedbytheenzyme25OHD-
1-α-hydroxylase(CYP27B1),to
produce1,25-(OH)2D3(calcitriol).
ThemostactiveVDmetaboliteand
hormonalform.
Figure 1.3: Biosynthesis of calcitriol hormone
https://www.researchgate.net

7. Calcitrioleffectthreetargettissue.
Theintestineisoneofthetargetorgans;intestinalcalcium
absorptionisstimulatedby1,25(OH)2D3(Calcitriol).
Becauseofthebalancebetweentranscellularandparacellular
intestinalabsorption,thisactionisdependentonthepresenceof
dietarycalcium,itsintestinalsolubility,andintestinalabsorptive
capacity(Donatietal.,2023).
Control of Phosphate and Calcium Homeostasis

8. Therearethreecomponentsto
transcellulartransport:
Calciumentranceviathebrush
bordermembrane'sparticular
calciumchannels.
Intracellularmovementbycalbindin
protein.
Andactivecalciumtransport,mostly
throughparticularcarriers,tothe
circulationonthebasolateralsurface.
Figure 1.4: Intestinal calcium absorption.
https://www.researchgate.net.

9. Thekidneyisthesecondorgan,wherecalciumreabsorptionis
facilitatedinthedistalrenaltubulesbyPTHandcalcitriol.
Threeprocessesareimpactedbycalcitriol:
calciumentryviatheapicalmembrane.
calciumdiffusionviacalbamicin.
activetransportviathebasolateralmembrane.
Furthermore,vitaminDsuppressesphosphatereabsorptionin
twoways:
Directlythroughα-klothoinductionandindirectlythrough
increasedexpressionofFGF-23inosteocytes.

10. Bonesarethethird
targetwherecalcitriol
promotethereleaseof
calciumwiththehelp
ofPTH.
Furthermore,byraising
osteopontin and
pyrophosphatelevels,
vitaminDinhibitsbone
mineralization(Donati
etal.,2023).
Figure 1.5: regulation of calcium and phosphorus via
calcitriol
https://media.springernature.com.

11. TheIOMguidelinesstatethat20ng/mL(50nmol/L)isthe
minimumrecommendedcirculatingamountof25(OH)D3.
Definingtheidealserum25(OH)D3concentrationasbeinghigher
than30ng/mL(75nmol/L)forvitaminDstatus.
ThemostfrequentcauseofricketsinchildrenisavitaminD
deficiency.
AdultswithpersistentvitaminDinsufficiencyordeficiency
experience:
Decreasedbonedensity,osteomalacia,andosteoporosis.
Theyalsohaveagreatlyincreasedriskofhipandtotalfractures.
Vitamin D Insufficiency and Associated Conditions

12. It is risk factor for
number of human
illnesses including
Cardiovascular diseases
Infections
Multiple cancer types
Heart failure (HF)
Atrial fibrillation (AF)
Coronary artery disease

13. VitaminDhaseffectonthewhitebloodcells.
VitaminDsupplementationalongwithOmega3fattyacids
reducetheriskofautoimmunediseasesby22%.
Italsohaveanticancerproperties.
Higherserumlevelsofcalcitriolatdiagnosishavereportedly
beenassociatedwithextendedcancerpatientsurvival.
Furthermore,ameta-analysisrevealedacorrelationbetween
lowcalcitriollevelsandbreastcanceratdiagnosis(Donatiet
al.,2023).

14. Up and down regulation of calcitriol
In chronic kidney disease
Inchronickidneydiseasethereislossofkidneytissue.
Thereislowlevelofcalcitriolbecauseoflossof1α-
hydroxylaseenzyme.
ThisenzymeisresponsibleforactivationofVitaminDinto
calcitriol.
Thisconditionleadstohypocalcemiaandsecondary
hyperparathyroidism(Shen,Y.(2023).
InCKDafeedbackloopexistbetweenFGF23andvitaminD.

15. OsteocytesincreasetheirreleaseofFGF23inresponsetotheir
feelingofhighbloodphosphorus.
HighlevelsofFGF23causeinhibitionof1α-hydroxylase
enzyme.
Andinducetheactivityof24-hydroxylasewhichReduced
1,25(OH)2Ddegradation.
Bydownregulating1α-hydroxylaseexpressionandupregulating
calcium-selectivechannelproteins,
thisleadstoanincreaseincalciumreabsorptioninthedistal
tubuleandasuppressionofvitaminDsynthesis.(Shen,Y.(2023)

16. Figure 1.6: Regulation of calcium and phosphate during CKD
https://www.ncbi.nlm.nih.gov/books.

17. In pregnancy
Themainactivityofcalcitriolduringpregnancyare
Increasecalciumabsorption.
Upregulateplacentalcalciumtransport.
Itenhancestheinnateimmuneresponseandinhibitsinflammation
thathasgottenworse.
Calcitriolaccomplishesthisby:
Causingthefetoplacentalunittoproducethepowerful
antimicrobialpeptidehCTD
Suppressingpro-inflammatorycytokineslikeTNF-α,IFN-γ,and
interleukin-6(IL-6)(Olmos-Ortizetal.,2015).

18. Thebiologicaleffectsofcalcitriolontheplacentaare:
Linkedtohormoneproductiongeneralplacentalphysiology.
Expressionofhumanchorionicgonadotropin
placentallactogenexpression.
Endometrialdecidualizationandthe
Synthesisofestradiolandprogesterone.
VitaminDinadequacy:
Gestationrelateddiseases.
Preeclampsia.
Gestationaldiabetes.
Indicationsforcesareansection(Mansuretal.,2022).

19. In skeletal muscle repair and growth
Calcium2+levelsandbonehealthmaintenanceareregulatedby
vitaminD.
VitaminD3isaremarkableimmunoregulatorthataffects:
Muscledamage
Aerobiccapacityandtheinflammatoryresponse.
RecentexperimentshavedemonstratedtheroleofvitaminDin
theregenerationofskeletalmuscle.
Inskeletalmuscle,calcitriolenterthetargetcellthroughmagalin-
cubilincomplex(Russo,Valle,&Malaguarnera,2023).

20. Thiscomplexattachwith
cytoplasmicactin.
ItenterthroughVDR.
TheinteractionofvitaminDto
VDRhelpinabsorptionof
inorganicphosphates.
Ithelpinmusclecontractility.
TheVDRalsohelpinprotein
synthesisandincreasemuscle
volume.
Figure 1.7: calcitriol entry into actin
https://www.researchgate.net

21. Incaseofmuscleinjury
VDRandCYP27B1expression
increasesignificantly.
Thesatellitecellsarecapableof
regeneration.
Satellitecellsundergoasymmetric
division.
Alsohelpincellulardifferentiation.
LowlevelsofvitaminDcause:
Reducedmusclemass.
Weakness.
Higherchanceofsarcopenia.
(Russo,Valle,&Malaguarnera,2023).
Figure 1.8 muscle regeneration.
https://www.frontiersin.org

22. References
Donati,S.,Marini,F.,Giusti,F.,Palmini,G.,Aurilia,C.,Falsetti,I.,...&Brandi,M.L.(2023).
Calcifediol:Why,When,HowMuch?.Pharmaceuticals,16(5),637.
Donati,S.,Palmini,G.,Aurilia,C.,Falsetti,I.,Marini,F.,Giusti,F.,...&Brandi,M.L.
(2023).Calcifediol:MechanismsofAction.Nutrients,15(20),4409.
Mansur,J.L.,Oliveri,B.,Giacoia,E.,Fusaro,D.,&Costanzo,P.R.(2022).VitaminD:
before,duringandafterpregnancy:effectonneonatesandchildren.Nutrients,14(9),
1900.
Olmos-Ortiz,A.,Avila,E.,Durand-Carbajal,M.,&Díaz,L.(2015).Regulationofcalcitriol
biosynthesisandactivity:focusongestationalvitaminDdeficiencyandadverse
pregnancyoutcomes.Nutrients,7(1),443-480.
Russo,C.,Valle,M.S.,&Malaguarnera,L.(2023).AntioxidativeeffectsofvitaminDin
muscledysfunction.RedoxExperimentalMedicine,2023(1)
Shen,Y.(2023).Minireview:AreevaluationofnutritionalvitaminDinthetreatmentof
chronickidneydisease.Medicine,102(43),e35811.