SEX HORMONE EFFECTS ON INTESTINAL CALCIUM ABSORPTION

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The objective of the research is to determine the effects of female hormone status on the intestinal Ca absorption. The intestinal absorption of Ca is altered in several physiological states that are also associated with changes in circulating sex hormone concentrations such as sexual maturation, pregnancy, lactation and aging. Three series of experiments have been designed to test various aspects of the hypothesis that estrogen can modulate intestinal Ca absorption. First, experiments will be conducted to determine whether estrogen has direct or indirect effects on intestinal Ca absorption. These studies will be carried out in both mature, cycling female rats and in young, maturing females in order to determine possible sex hormone effects on the intestinal maturation process as well as on the mature intestine. Ca transport by everted gut sacs of duodenum and other intestinal segments will be correlated with circulating concentrations of Ca, P, estradiol, and progesterone. Prolactin, parathyroid hormone, and calcitonin will also be measured in some experiments. These parameters will be compared between ovariectomized (ovx) and intact animals on low Ca (O.02%) and normal Ca (0.50%) diets. Hormone replacement and drug treatments with clomiphene and bromocriptine will then be used to determine whether estrogen has a direct effect on intestinal Ca transport or, if not, what the direct effector is. The second series of experiments is designed to determine alterations in intestinal Ca absorption due to naturally occurring alterations in sex hormones during pregnancy, lactation, sexual maturation, various stages of the estrus cycle and aging. Animals undergoing these processes will be fed either the normal or low Ca diet and studied using the methodology described for the earlier experiments. The final group of proposed experiments will determine whether sex hormone effects on intestinal Ca absorption are mediated via vitamin D metabolism, intestinal hypertrophy, or direct interaction with cellular Ca transport processes. The results of these experiments will increase our knowledge of the role of sex hormones in regulating intestinal Ca absorption in a variety of normal physiological conditions such as sexual maturation, pregnancy, lactation, and menopause which are all known to be associated with alterations in Ca metabolism. In addition, the prevention and treatment of postmenopausal osteoporosis will be facilitated when we know what effects sex hormone status has on intestinal Ca absorption.