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H L Henry

Publications and source records attributed to H L Henry.

67 records · Page 4Linked to original sources
PubMed1976

Biological activity of 24,25-dihydroxycholecalciferol in chicks and rats.

The ability of 24R, 25- and 24S, 25-dihydroxycholecalciferol to stimulate intestinal calcium transport and bone calcium mobilization in chicks was measured. Enhancement of intestinal calcium transport by 325 or 130 nmoles of either compound was maximal by 24 hours. The effects of these compounds on bone calcium mobilization were also maximal by 24 to 36 hours. When lower doses were tested, 2 nmoles of the 24R, 25-dihydroxycholecalciferol significantly stimulated intestinal calcium transport, whereas 130 nmoles of the S isomer were required for a significant response. Neither steroid had a significant effect on bone calcium mobilization when doses of less than 130 nmoles were given. When chicks received orally 32.5, 325 or 1,625 pmoles of 24R, 25-dihydroxycholecalciferol daily from hatching for 4 weeks, several parameters showed a dose-related response. These included growth, serum calcium, bone ash, renal 25-hydroxycholecalciferol-1-hydroxylase and intestinal vitamin D-dependent calcium binding protein. Rats given 32.5 to 1,625 pmoles of 24R, 25-dihydroxycholecalciferol for 3 or 6 weeks were equivalent to vitamin D-treated controls in terms of growth and serum calcium levels. It is concluded that within the lower dose ranges (2 to 30 pmoles) the R isomer of 24,25-dihydroxycholecalciferol is more active in stimulating intestinal calcium transport than the S isomer but that neither compound increases bone calcium mobilization at these dose levels. Also, the rat is more responsive in terms of growth and serum calcium, to small dialy doses of 24R, 25-dihydroxycholecalciferol than is the chick.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1976

1alpha,25-dihydroxyvitamin D3-like component present in the plant Solanum glaucophyllum.

The ability of an aqueous extract prepared from dried leaves of the South American shrub Solanum glaucophyllum to interact with a chick intestinal receptor system highly specific for the biologically active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), was monitored under both in vivo and in vitro conditions. The pretreatment of chicks with the S. glaucophyllum extract reduced the amount of subsequently administered radioactive 1alpha, 25-dihydroxyvitamin D3 localized in the intestinal chromatin fraction by 90% when compared with vitamin D-deficient controls. In addition, the active principle in the aqueous extract was found to compete effectively with 1alpha, 25-(OH)2D3 in a reconstituted intestinal receptor system in vitro. The plant factor(s) was found to be as effective as 1alpha, 25-(OH)2D3 in decreasing the renal 25-hydroxycholecalciferol-1alpha hydroxylase activity levels when administered to vitamin D-deficient chicks. By means of the in vitro intestinal receptor assay, it was possible to estimate that there are approximately 10 to 60 mg of the biologically active material in one kilogram of dries S. glaucophyllum leaves. These data indicate that the plant factor(s) may be a structural analog of 1alpha, 25-(OH)2D3 and suggest the feasibility of its isolation.

Animals↗
PubMedDate not supplied

The 25(OH)D(3)/1alpha,25(OH)(2)D(3)-24R-hydroxylase: a catabolic or biosynthetic enzyme?

The kidney is the major source of the circulating dihydroxylated metabolites of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25-dihydroxyvitamin D(3) [24R,25(OH)(2)D(3)]. The enzymes which catalyze the production of these two dihydroxylated vitamin D metabolites are the 25(OH)D(3)-1alpha-hydroxylase (1alpha-hydroxylase) and -24R-hydroxylase (24R-hydroxylase), respectively. While there is no controversy regarding the fundamental importance of the 1alpha-hydroxylase in the production of the steroid hormone 1alpha,25(OH)(2)D(3), the biologic significance of the 24R-hydroxylase has been the subject of ongoing discussion. Some hold that it is strictly catabolic, leading to side chain oxidation and cleavage of 25-hydroxylated vitamin D sterols, and others hold that it plays a biosynthetic role in the production of 24R,25(OH)(2)D(3) which has biologic activities distinct from those of 1alpha,25(OH)(2)D(3). The 24R-hydroxylase has properties in common with other multicatalytic steroidogenic enzymes: (1) the enzyme carries out multiple oxidative and carbon-carbon bond cleavages; (2) it utilizes two natural substrates; (3) its regulation varies depending on the cell or tissue in which it occurs. The purpose of this paper is to review the current literature relevant to the characteristics of the 24R-hydroxylase and its regulation in the context of other multicatalytic steroid hydroxylases in order to provide a perspective regarding its possible function as both a catabolic and activating enzyme in the vitamin D endocrine system.

Animals↗
PubMedDate not supplied

Different shapes of the steroid hormone 1alpha,25(OH)(2)-vitamin D(3) act as agonists for two different receptors in the vitamin D endocrine system to mediate genomic and rapid responses.

Vitamin D(3) produces biologic responses as a consequence of its metabolism into 1alpha,25(OH)(2)-vitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25(OH)(2)-vitamin D(3). The metabolic production of these two seco steroids and their generation of the plethora of biologic actions that are attributable to the parent vitamin D(3) are orchestrated via the integrated operation of the vitamin D endocrine system. This system is very similar in its organization to that of classic endocrine systems and is characterized by an endocrine gland (the kidney, the source of the two steroid hormones), target cells which possess receptors for the steroid hormones, and a feed-back loop involving changes in serum Ca(2+) that alter the secretion of parathyroid hormone (a stimulator of the renal 1-hydroxylase) which modulates the output by the kidney of the steroid hormones. There are, however, at least two unique aspects to the vitamin D endocrine system. (a) The chemical structures of vitamin D and its steroid hormones dictate that these be highly conformationally flexible molecules present a wide variety of shapes to their biologic environments. (b) It is now believed that 1alpha,25(OH)(2)D(3) produces biologic responses through two distinct receptors which recognize totally different shapes of the conformationally flexible 1alpha,25(OH)(2)D(3). Thus, the classic actions of 1alpha,25(OH)(2)D(3) to regulate gene transcription occur as a consequence of the stereospecific interaction of a modified 6-s-trans bowl-shape of 1alpha,25(OH)(2)D(3) with its nuclear receptor (VDR(nuc)). The ability of 1alpha,25(OH)(2)D(3) to generate a variety of rapid (seconds to minutes) biologic responses (opening of chloride channels, activation of PKC and MAP kinases) requires a planar 6-s-cis ligand shape which is recognized by a putative plasma membrane receptor (VDR(mem)) to initiate appropriate signal transduction pathways. This report summarizes the evidence for the specificity of different ligand shapes and the operation of the two receptor families for 1alpha,25(OH)(2)D(3).

Animals↗