Biochemical properties of A-homovitamin D derivatives: 1,4-dihydroxy-3-deoxy-A-homo-19-nor-9, 10-secocholesta-5,7-dienes

A study has been made in the chick of the stereostructural requirements of A-ring-functionalized vitamin D analogs which elicit vitamin D₃ and 1,25-(OH)₂D₃-dependent biological responses of intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Ring expansion of vitamin D₃ to produce (1S,4S), (1S,4R), or (1R,4S)-(7E)-1,4-dihydroxy-3-deoxy-A-homo-19-nor-9,10-secocholesta-5,7-dienes resulted in the loss of both ICA and BCM biological activity at dose levels of steroid of up to 650 nmol/0.1 kg birds. Accordingly the three A-homo analogs of vitamin D₃ were assessed for their ability to inhibit or increase the ICA or BCM responses of D₃ and 1,25-(OH)₂D₃. Only (1R,4S)-(7E)-diol-C, maintaining a cis-β,β-hydroxyl orientation showed antagonistic biological activity. Intraperitoneal doses (65–325 nmol) of diol-C administered in conjunction with D₃ (0.8–3.25 nmol) inhibited the BCM responses selectively and had no effect on the ICA response. Doses of analog-C (16.3-3.25 nmol) injected before and after the active hormone 1,25-(OH)₂D₃ (0.13–01.30 nmol) stimulated the ICA response of the latter above its normal levels (a synergistic response) when administered alone.