Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69 -90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n ‫؍‬ 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18 -68) also underwent BMD testing and VDR genotyping (n ‫؍‬ 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7-12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes <500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p < 0.05) in the bb genotype group compared with the BB group and 11% higher (p < 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The finding of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects. (J Bone Miner

No abstract

Both guanosine 5'-triphosphate (GTP) AND 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase (EC4.6.1.1) in chick kidney plasma membranes. Half-maximal stimulation occurred at 3-1 X 10(-6)M for both agents. The maximum increases in adenylate cyclase activity produced by GTP and Gpp(NH)p were respectively 130 and 720% over basal activity. At the end of a 12 min incubation period GTP concentration was 85% of that originally added in the presence of an ATP-regenerating system but less than 20% in its absence. GTP and guanosine 5'-diphosphate inhibited the activation of adenylate cyclase by Gpp(NH)p, suggesting that they all acted at a common site. Gpp(NH)p facilitated the stimulation of adenylate cyclase activity by bovine parathyroid hormone (BPTH) and by the synthetic amino terminal fragment BPTH (1-34), decreasing the concentrations required for half-maximal enzyme activation by a factor of approximately eight in both cases. This property was not shared by the native nucleotide GTP. Gpp(NH)p rendered active (at certain concentrations) a synthetic parathyroid hormone peptide fragment, BPTH (2-34), which was incapable of Activating adenylate cyclase in the absence of the nucleotide analogue. This suggested that the GTP analogue, in addition to a direct effect upon adenylate cyclase activity, was capable of influencing hormone interaction with the enzyme complex.

Adenylate cyclase activity of crude plasma membranes from chick kidney was stimulated by low doses of parathyroid hormone (PTH). Sensitivity to PTH was ten to twenty times greater than that of a similar preparation from rat kidney cortex. Synthetic peptides consisting of the NH2-terminal 34 amino acids of bovine PTH (BPTH) and of human PTH (HPTH) were assayed, as were several analogues of these peptides. Bovine PTH (1\p=n-\34) and HPTH (1\p=n-\34) were equivalent in their action on chick kidney but the human peptide had only 20 % of the activity of the bovine peptide on rat kidney cortex adenylate cyclase. Bovine proPTH ( \m=-\6\ar=r\+ 34) and (Tyr1)\ x=req-\ BPTH (1\p=n-\34) had less activity than BPTH (1\p=n-\34). Bovine PTH (2\p=n-\34) inhibited the response to BPTH (1\p=n-\34). Neither salmon calcitonin nor vasopressin stimulated adenylate cyclase activity.