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.  Calcitriol or bioactive form of vitamin D is a steroid hormone.
 In human body it helps to regulate the calcium and phosphorus
levels.
 And also help in the mineralization of bones.
 Calcitriol is the active form of vitamin D produced from its
precursor calcidiol in the kidney.
 It is implicated in a number of physiological and pathological
processes, including the metabolic syndrome, cancer, immune
system regulation, and cardiovascular disorders.(Donati et
al.,2023).
Introduction

4.  It work through VDR( vitamin D
receptors).
 They control a wide range of target
genes and, in turn, several cellular
processes.
 VDRs are expressed in practically all
human cell types.
 They affect the transcription of
roughly 3% of human genes.
Figure 1.1: Vitamin D receptors VDR
https://www.researchgate.net

5.  The primary source of vitamin D is
the sun's ultraviolet B rays, produced
in the epidermal layers and mostly in
the 290–320 nm spectral region.
 Sunlight's UVB rays bioconvert 7-
dehydrocholesterol to pre-vitamin
D3.
 Which is then thermally isomerized
to produce vitamin D in the skin.
 After the formation of VD in the
skin it is released into the blood
stream(Donati et al.,2023).
Figure 1.2: UV B radiations entering the skin
https://images.squarespace-cdn.com.

6.  With the help of VD binding proteins
it is transported to liver.
 It transformed into 25-hydroxyvitamin
D (calcidiol, 25OHD).
 Calcidiol is not the active form so it
move to kidney.
 It is mediated by the enzyme 25OHD-
1-α-hydroxylase (CYP27B1), to
produce 1,25-(OH)2D3 (calcitriol).
 The most active VD metabolite and
hormonal form.
Figure 1.3: Biosynthesis of calcitriol hormone
https://www.researchgate.net

7.  Calcitriol effect three target tissue.
 The intestine is one of the target organs; intestinal calcium
absorption is stimulated by 1,25(OH)2D3(Calcitriol).
 Because of the balance between transcellular and paracellular
intestinal absorption, this action is dependent on the presence of
dietary calcium, its intestinal solubility, and intestinal absorptive
capacity ( Donati et al.,2023).
Control of Phosphate and Calcium Homeostasis

8.  There are three components to
transcellular transport:
 Calcium entrance via the brush
border membrane's particular
calcium channels.
 Intracellular movement by calbindin
protein.
 And active calcium transport, mostly
through particular carriers, to the
circulation on the basolateral surface.
Figure 1.4: Intestinal calcium absorption.
https://www.researchgate.net.

9.  The kidney is the second organ, where calcium reabsorption is
facilitated in the distal renal tubules by PTH and calcitriol.
 Three processes are impacted by calcitriol:
 calcium entry via the apical membrane.
 calcium diffusion via calbamicin.
 active transport via the basolateral membrane.
 Furthermore, vitamin D suppresses phosphate reabsorption in
two ways:
 Directly through α-klotho induction and indirectly through
increased expression of FGF-23 in osteocytes.

10.  Bones are the third
target where calcitriol
promote the release of
calcium with the help
of PTH.
 Furthermore, by raising
osteopontin and
pyrophosphate levels,
vitamin D inhibits bone
mineralization(Donati
et al.,2023).
Figure 1.5: regulation of calcium and phosphorus via
calcitriol
https://media.springernature.com.

11.  The IOM guidelines state that 20 ng/mL (50 nmol/L) is the
minimum recommended circulating amount of 25(OH)D3.
 Defining the ideal serum 25(OH)D3 concentration as being higher
than 30 ng/mL (75 nmol/L) for vitamin D status.
 The most frequent cause of rickets in children is a vitamin D
deficiency.
 Adults with persistent vitamin D insufficiency or deficiency
experience:
 Decreased bone density, osteomalacia, and osteoporosis.
 They also have a greatly increased risk of hip and total fractures.
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.  Vitamin D has effect on the white blood cells.
 Vitamin D supplementation along with Omega 3 fatty acids
reduce the risk of autoimmune diseases by 22%.
 It also have anti cancer properties.
 Higher serum levels of calcitriol at diagnosis have reportedly
been associated with extended cancer patient survival.
 Furthermore, a meta-analysis revealed a correlation between
low calcitriol levels and breast cancer at diagnosis (Donati et
al.,2023).

14. Up and down regulation of calcitriol
In chronic kidney disease
 In chronic kidney disease there is loss of kidney tissue.
 There is low level of calcitriol because of loss of 1α-
hydroxylase enzyme.
 This enzyme is responsible for activation of Vitamin D into
calcitriol.
 This condition leads to hypocalcemia and secondary
hyperparathyroidism (Shen, Y. (2023).
 In CKD a feedback loop exist between FGF 23 and vitamin D.

15.  Osteocytes increase their release of FGF23 in response to their
feeling of high blood phosphorus.
 High levels of FGF23 cause inhibition of 1α-hydroxylase
enzyme.
 And induce the activity of 24-hydroxylase which Reduced
1,25(OH)2 D degradation.
 By downregulating 1α-hydroxylase expression and upregulating
calcium-selective channel proteins,
 this leads to an increase in calcium reabsorption in the distal
tubule and a suppression of vitamin D synthesis. (Shen, Y. (2023)

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

17. In pregnancy
 The main activity of calcitriol during pregnancy are
 Increase calcium absorption.
 Upregulate placental calcium transport.
 It enhances the innate immune response and inhibits inflammation
that has gotten worse.
 Calcitriol accomplishes this by:
 Causing the fetoplacental unit to produce the powerful
antimicrobial peptide hCTD
 Suppressing pro-inflammatory cytokines like TNF-α, IFN-γ, and
interleukin-6 (IL-6) (Olmos-Ortiz et al., 2015).

18.  The biological effects of calcitriol on the placenta are:
 Linked to hormone production general placental physiology.
 Expression of human chorionic gonadotropin
 placental lactogen expression.
 Endometrial decidualization and the
 Synthesis of estradiol and progesterone.
 Vitamin D inadequacy:
 Gestation related diseases.
 Preeclampsia.
 Gestational diabetes.
 Indications for cesarean section (Mansur et al., 2022).

19. In skeletal muscle repair and growth
 Calcium2+ levels and bone health maintenance are regulated by
vitamin D.
 Vitamin D3 is a remarkable immunoregulator that affects:
 Muscle damage
 Aerobic capacity and the inflammatory response.
 Recent experiments have demonstrated the role of vitamin D in
the regeneration of skeletal muscle.
 In skeletal muscle, calcitriol enter the target cell through magalin-
cubilin complex (Russo,Valle, & Malaguarnera,2023).

20.  This complex attach with
cytoplasmic actin.
 It enter through VDR.
 The interaction of vitamin D to
VDR help in absorption of
inorganic phosphates.
 It help in muscle contractility.
 The VDR also help in protein
synthesis and increase muscle
volume.
Figure 1.7: calcitriol entry into actin
https://www.researchgate.net

21.  In case of muscle injury
 VDR and CYP27B1 expression
increase significantly.
 The satellite cells are capable of
regeneration.
 Satellite cells undergo asymmetric
division.
 Also help in cellular differentiation.
 Low levels of vitamin D cause:
 Reduced muscle mass.
 Weakness.
 Higher chance of sarcopenia.
(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, How Much?. Pharmaceuticals, 16(5), 637.
 Donati, S., Palmini, G., Aurilia, C., Falsetti, I., Marini, F., Giusti, F., ... & Brandi, M. L.
(2023). Calcifediol: Mechanisms of Action. Nutrients, 15(20), 4409.
 Mansur, J. L., Oliveri, B., Giacoia, E., Fusaro, D., & Costanzo, P. R. (2022). Vitamin D:
before, during and after pregnancy: effect on neonates and children. Nutrients, 14(9),
1900.
 Olmos-Ortiz, A., Avila, E., Durand-Carbajal, M., & Díaz, L. (2015). Regulation of calcitriol
biosynthesis and activity: focus on gestational vitamin D deficiency and adverse
pregnancy outcomes. Nutrients, 7(1), 443-480.
 Russo, C., Valle, M. S., & Malaguarnera, L. (2023). Antioxidative effects of vitamin D in
muscle dysfunction. Redox Experimental Medicine, 2023(1)
 Shen, Y. (2023). Mini review: A reevaluation of nutritional vitamin D in the treatment of
chronic kidney disease. Medicine, 102(43), e35811.