ESTROGEN EFFECTS ON THE RENAL HANDLING OF CALCIUM IN THE OVARIECTOMIZED PERFUSED RAT

Estrogen deficiency is a major cause of bone loss in women but the mec hanism is unclear. The ovariectomized (OVX) rat is a well recognized m odel for post-menopausal osteoporosis. In this study we have examined the effects of OVX and estrogen replacement in the OVX rat on the rena l handling of calcium in response to alterations in the calcium load i n the perfused rat. The interaction of estrogen administration and par athyroid hormone (PTH) was also examined in the OVX, parathyroidectomi zed (PTX) rat. Calcium or EDTA was infused into sham or OVX rats to ob tain a range of filtered calcium loads. The excretion of calcium, was compared to the filtered load for the data from both perfusions indica ting a lower calcium (P = 0.006) and sodium (P = 0.009) excretion in t he OVX rat. A similar result was seen in the OVX rat replaced with 20 mu g of estrogen valerate 48 and 24 hours prior to perfusion with calc ium excretion being greater with estrogen administration (P = 0.005) c ompared to vehicle alone. This was not observed in the parathyroidecto mized rat. Correlations between sodium and water reabsorption and calc ium and sodium reabsorption during perfusion indicate that the results of OVX were due primarily to proximal tubule effects. Prior to the pe rfusion experiment PTH (sham vs. OVX pmol/liter, mean +/- SD; 20 +/- 6 vs. 18 +/- 4) and calcitriol (128 +/- 85 vs. 97 +/- 74) were similar in both groups, indicating that the results were not dependent on calc itropic hormone effects. It is concluded that, in the perfused rat, OV X results in decreased excretion of calcium and sodium as a result of estrogen effects on the renal proximal tubule, an effect dependent on PTH. This effect is opposite to that found in postmenopausal women, pe rhaps due to the high filtered load of calcium used in the experimenta l design and species differences in the relative importance of proxima l versus distal calcium handling.