In the present study, the role of vitamin D in the regulation of estrogen s
ynthesis in gonads was investigated. Vitamin D receptor null mutant mice sh
owed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogene
sis were observed in the female, and decreased sperm count and decreased mo
tility with histological abnormality of the testis were observed in the mal
e. The aromatase activities in these mice were low in the ovary, testis, an
d epididymis at 24%, 58%, and 35% of the wild-type values, respectively. Th
e gene expression of aromatase was also reduced in these organs. Elevated s
erum 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 histologic
al abnormality in the male gonads as well as in the female. Calcium supplem
entation increased aromatase activity and partially corrected the hypogonad
ism. When the serum calcium concentration was kept in the normal range by s
upplementation, 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 sex
es. The action of vitamin D on estrogen biosynthesis was partially explaine
d by maintaining calcium homeostasis; however, direct regulation of the exp
ression of the aromatase gene should not be neglected.