This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kinuta, K. Articles by Seino, Y. Search for Related Content PubMed PubMed Citation Articles by Kinuta, K. Articles by Seino, Y.

Vitamin D Is an Important Factor in Estrogen Biosynthesis of Both Female and Male Gonads¹

Department of Pediatrics, Okayama University Medical School (K.K., H.T., T.M., K.A., Y.S.), Okayama 700-8558; and Institute of Molecular and Cellular Biosciences (S.K.), University of Tokyo, Tokyo 113-0032, Japan

Address all correspondence and requests for reprints to: Dr. Hiroyuki Tanaka, Department of Pediatrics, Okayama University Medical School, 2–5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: hrtanaka{at}hospital.okayama-u.ac.jp

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 and ß 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.

This article has been cited by other articles:

				G. Lurie, L. R. Wilkens, P. J. Thompson, K. E. McDuffie, M. E. Carney, K. Y. Terada, and M. T. Goodman Vitamin D Receptor Gene Polymorphisms and Epithelial Ovarian Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2566 - 2571. [Abstract] [Full Text] [PDF]

				P Vigano, D Lattuada, S Mangioni, L Ermellino, M Vignali, E Caporizzo, P Panina-Bordignon, M Besozzi, and A M Di Blasio Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. J. Mol. Endocrinol., June 1, 2006; 36(3): 415 - 424. [Abstract] [Full Text] [PDF]

				A. Enjuanes, N. Garcia-Giralt, A. Supervia, X. Nogues, S. Ruiz-Gaspa, M. Bustamante, L. Mellibovsky, D. Grinberg, S. Balcells, and A. Diez-Perez Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation Eur. J. Endocrinol., December 1, 2005; 153(6): 981 - 988. [Abstract] [Full Text] [PDF]

				L. Gennari, R. Nuti, and J. P. Bilezikian Aromatase Activity and Bone Homeostasis in Men J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5898 - 5907. [Abstract] [Full Text] [PDF]

				G. M. Zinser and J. Welsh Vitamin D receptor status alters mammary gland morphology and tumorigenesis in MMTV-neu mice Carcinogenesis, December 1, 2004; 25(12): 2361 - 2372. [Abstract] [Full Text] [PDF]

				E. M. Colin, A. G. Uitterlinden, J. B. J. Meurs, A. P. Bergink, M. Van De Klift, Y. Fang, P. P. Arp, A. Hofman, J. P. T. M. van Leeuwen, and H. A. P. Pols Interaction between Vitamin D Receptor Genotype and Estrogen Receptor {alpha} Genotype Influences Vertebral Fracture Risk J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3777 - 3784. [Abstract] [Full Text] [PDF]

				A. L. M. Sutton and P. N. MacDonald Vitamin D: More Than a "Bone-a-Fide" Hormone Mol. Endocrinol., May 1, 2003; 17(5): 777 - 791. [Abstract] [Full Text] [PDF]

				K. H. Burns and M. M. Matzuk Minireview: Genetic Models for the Study of Gonadotropin Actions Endocrinology, August 1, 2002; 143(8): 2823 - 2835. [Abstract] [Full Text] [PDF]

				R. G. Erben, D. W. Soegiarto, K. Weber, U. Zeitz, M. Lieberherr, R. Gniadecki, G. Moller, J. Adamski, and R. Balling Deletion of Deoxyribonucleic Acid Binding Domain of the Vitamin D Receptor Abrogates Genomic and Nongenomic Functions of Vitamin D Mol. Endocrinol., July 1, 2002; 16(7): 1524 - 1537. [Abstract] [Full Text] [PDF]

				D. Zehnder, K. N. Evans, M. D. Kilby, J. N. Bulmer, B. A. Innes, P. M. Stewart, and M. Hewison The Ontogeny of 25-Hydroxyvitamin D3 1{alpha}-Hydroxylase Expression in Human Placenta and Decidua Am. J. Pathol., July 1, 2002; 161(1): 105 - 114. [Abstract] [Full Text] [PDF]

				R. Varghese, A. D. Gagliardi, P. E. Bialek, S.-P. Yee, G. F. Wagner, and G. E. Dimattia Overexpression of Human Stanniocalcin Affects Growth and Reproduction in Transgenic Mice Endocrinology, March 1, 2002; 143(3): 868 - 876. [Abstract] [Full Text] [PDF]

				G. Zinser, K. Packman, and J. Welsh Vitamin D3 receptor ablation alters mammary gland morphogenesis Development, January 7, 2002; 129(13): 3067 - 3076. [Abstract] [Full Text] [PDF]

				L. O'Donnell, K. M. Robertson, M. E. Jones, and E. R. Simpson Estrogen and Spermatogenesis Endocr. Rev., June 1, 2001; 22(3): 289 - 318. [Abstract] [Full Text] [PDF]

				L. E. Johnson and H. F. DeLuca Vitamin D Receptor Null Mutant Mice Fed High Levels of Calcium Are Fertile J. Nutr., June 1, 2001; 131(6): 1787 - 1791. [Abstract] [Full Text]