0013-7227/92/1304-1763$03.00/O Endocrinology Copyright Q 1992 by The Endocrine
Remembrance: System
Vol. 130, No. 4 Printed in U.S.A.
Society
Discovery
of the Vitamin
Although the steroid nature of vitamin D should have suggested its hormonal nature, its discovery as a vitamin led to an expectation that it might act like other vitamins, i.e. as enzymatic cofactors. The first crack in this concept came when it became clear that the vitamin D molecule must be modified before it could function to elevate blood calcium, a discovery resulting from early metabolic work using chemically synthesized radiolabeled vitamin D3 of high specific activity (1). This led to the discovery of the liver produced 25hydroxyvitamin D3 which for a time was believed to be the functional form of vitamin Ds (2). Three laboratories contributed to the idea that 25-hydroxyvitamin Da is further metabolized before function (3-5). This metabolism occurs exclusively in the kidney (6). In 1970-1971, the active form of vitamin D was isolated from a target organ, the intestine, and chemically identified as lcq25dihydroxyvitamin Ds (7). Chemical syntheses proved the 1-hydroxyl to be in the cY-configuration (8). Thus, the active form of vitamin D originates in the kidney but has its function in intestine and bone. Therefore, lq25dihydroxyvitamin DS must be considered a hormone and the kidney as the endocrine gland. Most important was the discovery that the production of lq25dihydroxyvitamin DB is feedback regulated by serum calcium (9) through the parathyroid glands (lo12), clearly defining the vitamin D-based endocrine system. The full impact of this endocrine system is currently widely explored as is the molecular mechanism of action of la,25dihydroxyvitamin D3 and its regulation. Certainly the finding of a role for lq25dihydroxyvitamin Received October 3, 1991. “Remembrance” articles discuss people and events as remembered by the author. The opinion(s) expressed are solely those of the writer and do not reflect the view of the Journal or The Endocrine Society.
D Endocrine
D3 in differentiation, the immune system, reproduction, and other systems demonstrate the far-reaching importance of this recently arrived endocrine system. Hector F. DeLuca Department of Biochemistry University of Wisconsin-Madison References 1. Lund J, DeLuca HF 1966 Biologically active metabolite of vitamin DB from bone, liver, and blood serum. J Lipid Res 2739-744 2. Blunt JW, DeLuca HF, Schnoes HK 1966 25-Hydroxycholecalciferal: a biologically active metabolits of vitamin Da. Biochemistry 7~3317-3322 3. DeLuca HF 1970 Metabolism and function of vitamin D. In: DeLuca HF, Suttie JW (eds), The Fat-Soluble Vitamins. University of Wisconsin Press, Madison, pp 3-20 4. Lawson DEM, Wilson PW, Kodicek E 1969 Metabolism hf vitamin D. A new cholecalciferol metabolite, involving loss of hydrogen at C-l, in chick intestinal nuclei. Biochem J 115269-277 5. Haussler MR. Mvrtle JF. Norman AW 1966 The association of a metabolite of vitamin Ds with intestinal mucosa chromatin in uiuo. J Biol Chem 2434055-4064 6. Fraser DR, Kodicek E 1970 Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 226~764-766 7. Holick MF, Schnces HK, DeLuca HF. Suda T, Cousins RJ 1971 Isolation and identification of 1,25dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistrv l&27992604 6. Semmler EJ, Holick MF, Schnoes HK, DeLuca HF 1972 The synthesis of lcu,25dihydroxycholecalciferol: a metabolically active form of vitamin Dx. Tetrahedron Lett 40:4147-4X0 9. Boyle IT, Gray RW, DeLuca HF 1971 Regulation bv calcium of in uiuo synthesisbf 1,25dihydroxycholecalciferol and 2i,25dihydroxycholecalciferol. Proc Nat1 Acad Sci USA 68:2131-2134 10. Garabedian M, Holick MF, DeLuca HF, Boyle IT 1972 Control of 25-hydroxycholecalciferol metabolism by the parathyroid glands. Proc Nat1 Acad Sci USA 691673-1676 11. Fraser DR. Kodieck E 1973 Reaulation of 25hvdroxvcholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone. Nature 241:163-X6 12. Garabedian M, Tanaka Y, Holick MF, DeLuca HF 1974 Response of intestinal calcium transport and bone calcium mobilization to 1,25dihydroxyvitamin D3 in thyroparathyroidectomized rats. Endocrinology 94:1022-1027
1763
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 17:51 For personal use only. No other uses without permission. . All rights reserved.
Remembrance: System
Vol. 130, No. 4 Printed in U.S.A.
Society
Discovery
of the Vitamin
Although the steroid nature of vitamin D should have suggested its hormonal nature, its discovery as a vitamin led to an expectation that it might act like other vitamins, i.e. as enzymatic cofactors. The first crack in this concept came when it became clear that the vitamin D molecule must be modified before it could function to elevate blood calcium, a discovery resulting from early metabolic work using chemically synthesized radiolabeled vitamin D3 of high specific activity (1). This led to the discovery of the liver produced 25hydroxyvitamin D3 which for a time was believed to be the functional form of vitamin Ds (2). Three laboratories contributed to the idea that 25-hydroxyvitamin Da is further metabolized before function (3-5). This metabolism occurs exclusively in the kidney (6). In 1970-1971, the active form of vitamin D was isolated from a target organ, the intestine, and chemically identified as lcq25dihydroxyvitamin Ds (7). Chemical syntheses proved the 1-hydroxyl to be in the cY-configuration (8). Thus, the active form of vitamin D originates in the kidney but has its function in intestine and bone. Therefore, lq25dihydroxyvitamin DS must be considered a hormone and the kidney as the endocrine gland. Most important was the discovery that the production of lq25dihydroxyvitamin DB is feedback regulated by serum calcium (9) through the parathyroid glands (lo12), clearly defining the vitamin D-based endocrine system. The full impact of this endocrine system is currently widely explored as is the molecular mechanism of action of la,25dihydroxyvitamin D3 and its regulation. Certainly the finding of a role for lq25dihydroxyvitamin Received October 3, 1991. “Remembrance” articles discuss people and events as remembered by the author. The opinion(s) expressed are solely those of the writer and do not reflect the view of the Journal or The Endocrine Society.
D Endocrine
D3 in differentiation, the immune system, reproduction, and other systems demonstrate the far-reaching importance of this recently arrived endocrine system. Hector F. DeLuca Department of Biochemistry University of Wisconsin-Madison References 1. Lund J, DeLuca HF 1966 Biologically active metabolite of vitamin DB from bone, liver, and blood serum. J Lipid Res 2739-744 2. Blunt JW, DeLuca HF, Schnoes HK 1966 25-Hydroxycholecalciferal: a biologically active metabolits of vitamin Da. Biochemistry 7~3317-3322 3. DeLuca HF 1970 Metabolism and function of vitamin D. In: DeLuca HF, Suttie JW (eds), The Fat-Soluble Vitamins. University of Wisconsin Press, Madison, pp 3-20 4. Lawson DEM, Wilson PW, Kodicek E 1969 Metabolism hf vitamin D. A new cholecalciferol metabolite, involving loss of hydrogen at C-l, in chick intestinal nuclei. Biochem J 115269-277 5. Haussler MR. Mvrtle JF. Norman AW 1966 The association of a metabolite of vitamin Ds with intestinal mucosa chromatin in uiuo. J Biol Chem 2434055-4064 6. Fraser DR, Kodicek E 1970 Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 226~764-766 7. Holick MF, Schnces HK, DeLuca HF. Suda T, Cousins RJ 1971 Isolation and identification of 1,25dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistrv l&27992604 6. Semmler EJ, Holick MF, Schnoes HK, DeLuca HF 1972 The synthesis of lcu,25dihydroxycholecalciferol: a metabolically active form of vitamin Dx. Tetrahedron Lett 40:4147-4X0 9. Boyle IT, Gray RW, DeLuca HF 1971 Regulation bv calcium of in uiuo synthesisbf 1,25dihydroxycholecalciferol and 2i,25dihydroxycholecalciferol. Proc Nat1 Acad Sci USA 68:2131-2134 10. Garabedian M, Holick MF, DeLuca HF, Boyle IT 1972 Control of 25-hydroxycholecalciferol metabolism by the parathyroid glands. Proc Nat1 Acad Sci USA 691673-1676 11. Fraser DR. Kodieck E 1973 Reaulation of 25hvdroxvcholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone. Nature 241:163-X6 12. Garabedian M, Tanaka Y, Holick MF, DeLuca HF 1974 Response of intestinal calcium transport and bone calcium mobilization to 1,25dihydroxyvitamin D3 in thyroparathyroidectomized rats. Endocrinology 94:1022-1027
1763
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 17:51 For personal use only. No other uses without permission. . All rights reserved.
