Vitamin D Is an Important Factor in Estrogen Biosynthesis of Both Female and Male Gonads*

Abstract

In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor alpha and beta were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.

Tissue-Selective Regulation of Aromatase Expression by Calcitriol: Implications for Breast Cancer Therapy

“…Other studies in keratinocytes (34) and prostate cancer cells (35) found no effect of calcitriol on aromatase expression. Kinuta et al (36) reported histological abnormalities and decreases in aromatase activity and expression in the gonads of both female and male VDR null mice. Their results indicated that calcitriol plays a role in gonadal estrogen synthesis to a large extent by maintaining calcium homeostasis.…”

Current Understanding of Risk Factors for Ovarian Cancer

“…The vitamin D receptor (VCR) is a nuclear transcription factor that mediates most of the actions of vitamin D [104]. In an animal study, VDR-null mice exhibited gonadal insufficiency, had reduced aromatase gene expression and activity, and had elevated serum levels of luteinizing and follicle-stimulating hormones [105]. In humans, a study revealed evidence that polymorphisms in VDR genes might influence ovarian cancer susceptibility [104].…”

Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system

“…In the last years, interest in this specific topic has been greatly increased for two reasons: (i) the development of mice deficient in VDR or 1 -OHase has revealed that these animals show impaired ovarian folliculogenesis and uterine hypoplasia (Yoshizawa et al 1997, Kinuta et al 2000, Panda et al 2001 and (ii) vitamin D seems to influence the reproductive system not only at the ovarian level but also at the endometrial level. Indeed, some of the genes recently identified to be uniquely regulated at the site of embryo implantation, for instance calbindinD9k in the mouse and the homeobox (Hox) A10 gene in humans, are vitamin D-dependent proteins (Rots et al 1998, Nie et al 2000, Salamonsen et al 2002, Du et al 2005.…”