Abstract
Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The biological actions of VD in fertility and reproductive tissues have been investigated but mainly using animal models. Conversely, the molecular data addressing the mechanisms underlying VD action in the physiologic endometrium and in endometrial pathologies are still scant. Levels of VDR expression according to the menstrual cycle are yet to be definitively clarified, possibly being lower in the proliferative compared to the secretory phase and in mid-secretory compared to early secretory phase. Endometrial tissue also expresses the enzymes involved in the metabolism of VD. The potential anti-proliferative and anti-inflammatory effects of VD for the treatment of endometriosis have been investigated in recent years. Treatment of ectopic endometrial cells with 1,25(OH)2D3 could significantly reduce cytokine-mediated inflammatory responses. An alteration of VD metabolism in terms of increased 24-hydroxylase mRNA and protein expression has been demonstrated in endometrial cancer, albeit not consistently. The effect of the active form of the vitamin as an anti-proliferative, pro-apoptotic, anti-inflammatory, and differentiation-inducing agent has been demonstrated in various endometrial cancer cell lines.
Highlights
Vitamin D, Metabolism, and ReproductionVitamin D is a well-known steroid hormone whose activated form is the result of the conversion of 7-dehydrocholesterol in the skin, under the influence of ultraviolet B light
Encouraged by the aforementioned information, we aimed to present a systematic review on all available molecular data related to the effect of vitamin D (VD) in human endometrium and endometrial diseases, with a focus on endometriosis and endometrial cancer
They analyzed separately epithelial and stromal endometrial cells and reported that Vitamin D receptor (VDR) mRNA was significantly higher in epithelial compared to stromal cells isolated from endometrial biopsies from patients with endometriosis (p < 0.01) while this difference could not be detected in the endometrium from healthy controls patients
Summary
Vitamin D is a well-known steroid hormone whose activated form is the result of the conversion of 7-dehydrocholesterol in the skin, under the influence of ultraviolet B light To become active, it requires two hydroxylation steps: a 25-hydroxylation occurring mainly in the liver, leading to 25-hydroxyvitamin D3 (25-OHD3), and a 1α-hydroxylation occurring in the proximal tubules cells of the kidney, leading to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). It requires two hydroxylation steps: a 25-hydroxylation occurring mainly in the liver, leading to 25-hydroxyvitamin D3 (25-OHD3), and a 1α-hydroxylation occurring in the proximal tubules cells of the kidney, leading to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) All these hydroxylation steps are catalyzed by cytochrome P450 mixed-function oxidases that are produced by the CYP gene superfamily group. Encouraged by the aforementioned information, we aimed to present a systematic review on all available molecular data related to the effect of VD in human endometrium and endometrial diseases, with a focus on endometriosis and endometrial cancer
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