Submitted on August 24, 2006
Accepted on October 24, 2006
Ovariectomy Worsens Secondary Hyperparathyroidism in Mature Rats during Low Ca Diet
Yan Zhang1, Wan-Ping Lai2, Chun-Fu Wu3, Murray J. Favus4, Ping-Chung Leung5, and Man Sau Wong6*
1 State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, Guangtua, China
2 Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
3 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
4 Department of Medicine, University of Chicago, Chicago,, Illinois, United States
5 Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
6 Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
* To whom correspondence should be addressed. E-mail: bcmswong{at}polyu.edu.hk.
Estrogen deficiency impairs intestinal Ca absorption and induces bone loss, but its effects on vitamin D-endocrine system are unclear. In the present study, the calciotropic hormones levels, renal vitamin D metabolism, 1,25(OH)2D3-dependent intestinal calcium absorption and bone properties in three-month-old sham-operated (sham) or ovariectomized (OVX) rats fed either normal Ca (NCD, 0.6% Ca, 0.65% P) or low Ca (LCD, 0.1% Ca, 0.65% P) diet for 2 weeks were determined. LCD increased serum 1,25(OH)2D3 levels in both sham and OVX rats. Serum parathyroid hormone (PTH 1-84) levels were highest in OVX rats fed LCD. Renal 25-hydroxyvitamin D 1-alpha hydroxylase (1-OHase) protein expression was induced in both Sham and OVX rats during LCD; while renal 1-OHase mRNA expression was highest in OVX rats fed LCD. Renal vitamin D receptor (VDR) and mRNA expression in rats were induced by ovariectomy in rats fed NCD but suppressed by ovariectomy in rats fed LCD. The induction of intestinal calcium transporter 1 and calbindin-D9K mRNA expressions by LCD were not altered by ovariectomy. As expected, bone Ca content, cancellous bone mineral density and bone strength index in proximal metaphysis of rat tibia were reduced by both ovariectomy and LCD (P < 0.05) as analyzed by two-way ANOVA. Taken together, ovariectomy alters the responses of circulating PTH levels, renal 1-OHase mRNA expression and renal VDR expression to LCD. These results suggest that estrogen is necessary for the full adaptive response to LCD mediated by both PTH and 1,25(OH)2D3.
