The general objectives of the research are to a) characterize the regulation of intestinal calcium absorption and parathyroid hormone secretion during lactation and b) characterize the regulation of synthesis and circulating levels of 1, 25- dihydroxyvitamin D3 during lactation and the neonatal period. Regulation of intestinal calcium absorption will be determined by a) measuring active calcium transport (using everted gut sacs in vitro) and the content of the vitamin D-dependent calcium- binding protein (9 KD CaBP) in the duodenum and ileum of rats during pregnancy and lactation, and b) measuring nonsaturable calcium transport in the jejunum and ileum (with everted gut sacs and Ussing chambers) of lactating rats. Hypotheses to be tested are: (1) duodenal CaBP and active calcium transport in lactation are independent of 1, 25-(OH)2D3 but stimulated by prolactin or another lactation-related hormone, (2) nonsaturable calcium transport in the jejunum and ileum is enhanced during lactation because of lactation-mediated structural changes in the intestinal epithelium. Parathyroid hormone (PTH) secretion will be examined during lactation by determining a) the plasma PTH level by an N-terminal-specific radioimmunoassay (RIA), and b) the rate of release of PTH in vitro from parathyroid cells from lactating rats using an osteosarcoma cell cAMP bioassay for PTH. The potential roles of secretin and corticosterone in enhancing PTH secretion during lactation will be tested by the in vitro PTH release procedure, and the effects of the suckling stimulus and fasting/refeeding will be determined by RIA of plasma PTH. The results may reveal the involvement of factors other than hypocalcemia in maintaining elevated plasma PTH levels during lactation. The control of 1, 25-(OH)2D3 synthesis during lactation and postnatal development will be determined by a renal 25- OHD3-1-hydroxylase assay. Since plasma 1,25-(OH)2D3 in rat pups increases markedly between 2 and 5 weeks of age, while plasma PTH does not change, it is proposed that the rise in plasma 1, 25-(OH)2D3 during this period is due to increasing sensitivity of the renal 25-OHD3-1-hydroxylase enzyme activity to PTH. The proposed work with lactating rats may indicate a role of prolactin in stimulating the renal 25-OHD3-1-hydroxylase. The results of the proposed studies will reveal regulatory factors and adaptive mechanisms that come into play when calcium demands are increased markedly for both the lactating mother and the suckling and newly weaned offspring.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD012496-08
Application #
3311903
Study Section
General Medicine B Study Section (GMB)
Project Start
1980-04-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Boass, A; Toverud, S U (1997) Enhanced nonsaturable calcium transport in the jejunum of rats during lactation, but not during pregnancy. J Bone Miner Res 12:1577-83
Boass, A; Garner, S C; Schultz, V L et al. (1997) Regulation of serum calcitriol by serum ionized calcium in rats during pregnancy and lactation. J Bone Miner Res 12:909-14
Schultz, V L; Boass, A; Garner, S C et al. (1997) Altered regulation of parathyroid hormone secretion by calcium in pregnant and lactating rats. J Bone Miner Res 12:903-8
Boass, A; Toverud, S U (1996) Duodenal active calcium transport in female rats increases with serum calcitriol concentrations, but reaches a plateau far below maximal calcitriol levels. J Bone Miner Res 11:1640-5
Schultz, V L; Boass, A; Garner, S C et al. (1995) Several anesthetics, but not diethyl ether, cause marked elevation of serum parathyroid hormone concentration in rats. J Bone Miner Res 10:1298-302
Boass, A; Toverud, S U (1995) Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats. Am J Physiol 269:E934-9
Schultz, V L; Garner, S C; Lavigne, J R et al. (1994) Determination of bioactive rat parathyroid hormone (PTH) concentrations in vivo and in vitro by a 2-site homologous immunoradiometric assay. Bone Miner 27:121-32
Lobaugh, B; Garner, S C; Lovdal, J A et al. (1993) Parathyroidectomy abolishes the increase of renal 25-hydroxyvitamin D-1 alpha-hydroxylase in lactating rats. Am J Physiol 264:E981-5
Lobaugh, B; Boass, A; Garner, S C et al. (1992) Intensity of lactation modulates renal 1 alpha-hydroxylase and serum 1,25(OH)2D in rats. Am J Physiol 262:E840-4
Boass, A; Lovdal, J A; Toverud, S U (1992) Pregnancy- and lactation-induced changes in active intestinal calcium transport in rats. Am J Physiol 263:G127-34

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