Changes in calcium, PTH and 1,25(OH)2 vitamin D3 during tail-suspension in ovariectomized rats: Effects of estrogen administration

Abstract

It is well known that estrogen deficiency results in osteoporosis in human and experimental animals. However, how its deficiency affects the development of disuse atrophy is not well understood. In this study, the effects of estrogen deficiency caused by ovariectomy and estrogen supplements on serum levels of calcium, Parathyroid Hormone (PTH), and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in tail-suspended rats were investigated. Five-week-old female Wistar rats were ovariectomized and divided into two groups. One group received an intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received the vehicle alone (OVX group). After the third injection, the rats were subjected to tail-suspension in metabolic cages for one, three, five or seven days. In the OVX group, urinary excretion of deoxypyridinoline (D-Pyr) tended to increase on day one after tail-suspension. In the OVX-E2 group, basal excretion was lower than that in the OVX group, and no increase was observed after suspension. Serum concentrations of ionized calcium significantly increased on day one after the suspension in both groups. However, in the OVX-E2 group, the level tended to be higher than those in the OVX group from day zero to day three. Serum PTH tended to decrease on day one after suspension in the OVX group. In the OVX-E2 group, it did not change during the suspension, but the levels were higher than those in the OVX group during the experiment. Serum 1,25(OH)2D3 transiently and significantly increased on day one after suspension in both groups. However, in the OVX group, the level was significantly higher than that in the OVX-E2 group. These data indicate that estrogen treatment of ovariectomized rats modifies the changes in calcium metabolism induced by tail-suspension.

ヒトや実験動物において、エストロゲンの欠乏が骨粗鬆症に至ることは良く知られている。しかし、その欠乏がどのように非活動性萎縮に影響を及ぼすかは解明されていない。そこで今回、卵巣切除によるエストロゲン欠乏およびエストロゲン補充が尾懸垂ラットにおけるカルシウム、副甲状腺ホルモン(PTH)、1,25ジヒドロキシビタミンD3(1,25(OH)2D3)の血清濃度に及ぼす影響を検討した。5週齢のメスラットを卵巣切除処理し、2群に分けた。1群では週1回ジプロピオン酸エストラジオールの筋注を行い(OVX-E2群)、もう1群では賦形剤のみを投与した(OVX群)。3回目の投与後、ラットを代謝ケージに収容し、1、3、5、あるいは7日間にわたり尾懸垂試験を行った。OVX群では、尾懸垂後1日目にデオキシピリジノリン(D-Pyr)の尿中排泄量の増加傾向が認められた。OVX-E2群では、投与前のD-Pyr排泄量がOVX群に比べ低く、懸垂後も増加が認められなかった。血清カルシウムイオン濃度は両群において1日目に有意に上昇した。しかしOVX-E2群では、0日目から3日目まで血清カルシウムイオン濃度がOVX群に比べ高い傾向を示した。血清PTH濃度は懸垂後1日目にOVX群で低下傾向を示した。OVX-E2群では懸垂中の血清PTH濃度に変化は認められなかったが、血清PTH濃度は実験期間を通じてOVX群に比べ高かった。血清1,25(OH)2D3濃度では、懸垂後1日目に両群において一過性の有意な上昇が認められた。しかし血清1,25(OH)2D3濃度はOVX-E2群に比べOVX群で有意に高かった。この結果は、卵巣切除ラットへのエストロゲン投与は尾懸垂によるカルシウム代謝変化に影響を及ぼすことを、示している。