Vitamin D regulates estrogen biosynthesis through VDR’s
Direct regulation of the expression of the aromatase gene
Maintaining extracellular calcium homoeostasis
Vitamin D increases progesterone secretion by
Granulosa cell leutinisation – HOXA10 expression
Increased 3 β- HSD mRNA levels
Vitamin D increases placental sex steriod production
Regulates human chorionic expression
Secretion from human syncitiotrophoblasts (promoter- CYP19 )
2. Introduction
1, 25-Dihydroxy vitamin D3
(1,25 - [OH]2 D3) Calcitriol
25- Hydroxy vitamin D3
(25- OH D3)
Cholecalciferol
Inactive and
major
circulating form
Active form
25-Hydroxy vitamin D
1α-hydroxylase
(CYP27B1)
Mechanism of Action:
•Steroid hormone
•Binds to VDR in nucleus to up regulate gene expression in target cells
6. Vitamin D and Steroidgenesis
Vitamin D regulates estrogen biosynthesis through VDR’s
Direct regulation of the expression of the aromatase gene
Maintaining extracellular calcium homoeostasis
Vitamin D increases progesterone secretion by
Granulosa cell leutinisation – HOXA10 expression
Increased 3 β- HSD mRNA levels
Vitamin D increases placental sex steriod production
Regulates human chorionic expression
Secretion from human syncitiotrophoblasts (promoter- CYP19 )
7. Vitamin D and Follicular Development
Vitamin D allows follicles to reach terminal maturation and ovulation
Inhibiting AMH expression
Potentiates granulosa cell differentiation
Vitamin D maintains luteal phase
Decreases AMHR-II and FSHR gene expression
Potentiates LH hormone
Vitamin D positively co-related to AMH
Promoter for the AMH gene contains a vitamin D response element and vit D
upregulates AMH production
8. Vitamin D and PCOS
Vitamin D supplementation improves menstrual frequency and results in
higher number of dominant follicles
Vitamin D deficiency was independently associated with
Lower insulin sensitivity
Lower HDL-C levels
VDR associated polymorphisms
J Ott, L Wattar , C Kurz. Parameters for calcium metabolism in women
with polycystic ovary syndrome who undergo clomiphene citrate
stimulation: a prospective cohort study. European Journal of
Endocrinology (2012) 166 897–902
9. Vitamin D and Endometriosis
Endometrium as extra renal site of Vitamin D action
Expresses 1α Hydroxylase activity through VDR
Abundance of Vitamin D binding protein in Endometriosis ~3 times
Vitamin D Helps through immunomodulant action causing
implantation tolerance
Regulation of cytokine by NK cell
Attenuates decidual T cell function
Causes proper implantation
Up-regulates endometrial transcription factor
Denis et al .The level of serum anti-Müllerian
hormone correlates with vitamin D status in
men and women but not in boys. Rev
Endocrinol2012 May
10. Vitamin D and In Vitro Fertilisation
Higher levels of Vitamin D in follicular fluid was associated with better IVF
outcomes which also reflected body stores
Vitamin D causes significant increase in sRAGE levels counteracting
advanced glyation end products(AGEs) causing optimal follicular growth
Vitamin D is an independent predictive factor
for CC stimulation
Very high Vitamin D levels was associated with poor embryo quality
and lower clinical pregnancy rates
Oskan et al. Replete Vitamin D stores predict reproductive succes following IVF. Fertil &Steril 2010
11. Vitamin D and Male Reproduction
Androgen Status
Low Vitamin D associated with secondary and compensated hypogonadism
Concordant seasonal variation of testosterone
Semen parameters
Increases progressive sperm motility via VDR-mediated calcium release
Induces acrosome reaction
Testiculopathy
Testiculopathic patients showed osteopenia and osteoporosis
12. Vitamin D Supplementation
Adjunctive agent in therapies
Can be taken orally, relatively safe and cheap vitamin
Endocrine Practice guidelines committee
18 – 70 years- 1500 - 2000 IU daily
Upper limit – 10,000 IU daily
1000 IU/day increases Vitamin D levels 10ng/ml
Vitamin D intoxication resulting in hyper-calcemia , renal damage and
calcification was not observed until Vitamin D levels > 150 ng/ml
In humans, predominant source of vitamin D :
endogenous cutaneous synthesis
dietary sources contribute 20%
Nutritional forms consist of :
D3 (cholecalciferol)- found in fish (i.e. sardine, salmon and mackerel), eggs and calf liver, and
D2 (ergocalciferol)- UV irradiation of ergosterol from yeast and fungi (i.e. mushrooms).
Both forms are inactive and are efficiently absorbed by gut.
Dietary vitamin D is identical to the skin derived form.
Recently expression of CYP27B1 in non-renal tissues including placenta and decidua generating Vit D by local mechanisms.
In its
active form, vitamin D regulates expression of human chorionic gonadotropin (hCG) in
syncytiotrophoblasts and stimulates production of sex steroids.2