Summary
Evidence from autoradiographic studies with 3H 1,25(OH)2 vitamin D3 (soltriol) about its many sites of nuclear binding and multiple actions suggests that the traditional view of “vitamin D and calcium” is too limited and requires modification. A new concept has been developed which proposes that the skin-derived hormone of sunshine, soltriol, is a somatotrophic activator and modulator that affects all vital systems. Regulation of calcium homeostasis is only one of its many actions. Target tissues for soltriol include not only bone, intestine and kidney, but also brain, spinal cord, pituitary, thyroid, endocrine pancreas, adrenal medulla, enteroendocrine cells, thymus, and male and female reproductive organs. Accordingly, actions of soltriol involve effects on autonomic and endocrine regulation with changes in tissue and blood hormone levels, innervation of skeletal muscle, immune and stress response, digestion, blood formation, fertility, pregnancy and lactation, general energy metabolism, mental processes and mood, and others. The skin-mediated transduction of short-wave sunlight induces a purposeful modulation of growth, reproduction and other biological activities in tune with the conditions of the sun cycle and season. Synthesis and actions of vitamin D3-soltriol are dependent not only on the amount of sunlight, but also on the availability of precursor in the skin and access of sunlight, the rate of hydroxylation in liver and kidney, and the modulation of these events by the endocrine status, in particular growth and reproduction. A concept of a five-level control of soltriol synthesis is proposed, in which the hydroxylation steps provide for a sensitive tuning. Relationships between the heliogenic skin-derived hormonal system and the helioprivic pineal-derived hormonal system are recognized and a comprehensive concept of the “endocrinology of sunlight and darkness” is pointed out.
Similar content being viewed by others
References
Aksnes L, Aarskog D (1982) Plasma concentrations of vitamin D metabolites in puberty: effect of sexual maturation and implications for growth. J Clin Endocrinol Metab 55:94–101
Baksi SN, Kenney AD (1978) Does estradiol stimulate in vivo production of 1,25-dihydrovitamin D3 in the rat? Life Sci 22:787–791
Bastillo L, Tanaka Y, Wineland MJ, DeLuca HF (1979) Synergistic effect of progesterone, testosterone and estradiol in the stimulation of chick renal 25-hydroxy-vitamin D-1a-hydroxylase. Endocrinology 104:1598–1601
Bell NH (1985) Vitamin-D-endocrine system. J Clin Invest 76:1–6
Brumbaugh PF, Hughes MR, Haussler MR (1975) Cytoplasmic and nuclear binding components for 1a,25-dihydroxyvitamin D3 in chick parathyroid glands. Proc Natl Acad Sci USA 72:4871–4875
Christakos S, Norman AW (1980) Specific receptor/binding proteins for 1,25(OH)2-vitamin D3 in rat and human placenta. Fed Proc 39:560
Clark SA, Stumpf WE, Sar M, DeLuca HF, Tanaka Y (1980) Target cells for 1,25 dihydroxyvitamin D3 in the pancreas. Cell Tissue Res 209:515–520
Clark SA, Stumpf WE, Sar M (1981) Effects of 1,25 dihydroxyvitamin D3 on insulin secretion. Diabetes 30:382–386
Clark SA, Dame MC, Kim YS, Stumpf WE, DeLuca HF (1985) 1,25-Dihydroxyvitamin D3 in teeth of rats and humans: receptors and nuclear localization. Anat Rec 212:250–254
Clark SA, Boass A, Toverud SU (1986a) Development-related regulation of plasma 1,25(OH)2D3 concentration by calcium intake in rat pups. Bone Mineral 1:193–203
Clark SA, D'Ercole AJ, Toverud SU (1986b) Somatomedin-C/insulin-like growth factor I and vitamin-induced growth. Endocrinology 119:1660–1665
Clark SA, Stumpf WE, Bishop CW, DeLuca HF, Park DH, Joh TH (1986c) The adrenal: a new target organ of the calciotropic hormone 1,25 dihydroxyvitamin D3. Cell Tissue Res 234:299–302
Clark SA, Stumpf WE, Sar M, DeLuca HF (1987) 1,25-Dihydroxyvitamin D3 target cells in immature pancreatic islets. Am J Physiol 253:E99-E105
Colston K, Hirst M, Feldman D (1980) Organ distribution of the cytoplasmic 1,25 dihydroxycholecalciferol receptor in various mouse tissues. Endocrinology 107:1916–1922
Cooper CW, Schwesinger WH, Mahgoub AM, Ontjes DA (1971) Thyrocalcitonin: stimulation of secretion by pentagastrin. Science 172:1238–1240
Dokoh S, Donaldson CA, Marion SL, Pike JW, Haussler MR (1983) The ovary: a target for 1,25-dihydroxyvitamin D3. Endocrinology 112:200–206
Lij C, Marx SJ (1981) Nucleaer uptake of 1,25 dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin. Proc Natl Acad Sci USA 78:2562–2566
Esvelt RP, DeLuca HF, Wichman JK, Yishizawa S, Zurcher J, Sar M, Stumpf WE (1980) 1,25-Dihydroxyvitamin D3 stimulated increase of 7,8-didehydrocholesterol levels in rat skin. Biochemistry 19:6158–6161
Feldman D, Chen T, Hirst M, Colston K, Karasek M, Cone C (1980) Demonstration of 1,25-dihydroxyvitamin D3 receptors in human skin biopsies. J Clin Endocrinol Metab 51:1463–1465
Fraser DR, Kodicek E (1970) Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature 228:764–766
Gelbard HA, Stern PH, U'Prichard DC (1980) 1,25-Dihydroxyvitamin D3 nuclear receptors in pituitary. Science 209:1247–1249
Gray RW (1981) Effects of age and sex on the regulation of plasma 1,25-(OH)2-D by phosphorus in the rat. Calcif Tissue Int 33:477–484
Halloran BP, Barthell EN, DeLuca HF (1979) Vitamin D metabolism during pregnancy and lactation in the rat. Proc Natl Acad Sci USA 76:5549–5553
Haussler MR (1986) Vitamin D receptors: nature and function. Annu Rev Nutr 6:527–562
Haussler MR, Manolagas SC, Deftos LJ (1980) Evidence for a 1,25-dihydroxyvitamin D3 receptor-like macromolecule in rat pituitary. J Biol Chem 225:5007–5010
Haussler MR, Manolagas SC, Deftos LJ (1982) Receptor for 1,25-dihydroxyvitamin D3 in GH3 pituitary cells. J Steroid Biochem 16:15–19
Henry HL, Norman AW (1975) Studies on the mechanism of action of calciferol. VII. Localization of 1,25-dihydroxy-vitamin D3 in chick parathyroid glands. Biochem Biophys Res Commun 62:781–788
Herting DC, Steenbock H (1955) Vitamin D and gastric secretion. J Nutrit 57:469–482
Holick MF (1984) The photobiology of vitamin D3 in man. In: Kumar R (ed) Vitamin D. Basic and clinical aspects. Martinus Nijhoff, Boston, pp 197–216
Hosomi J, Hosoi J, Abe E, Suda T, Kuroki T (1983) Regulation of terminal differentiation of cultured mouse epidermal cells by 1a,25-dihydroxyvitamin D3. Endocrinology 113:1950–1957
Hughes MR, Haussler MR (1978) 1,25-Dihydroxyvitamin D3 receptors in parathyroid glands: preliminary characterization of cytoplasmic and nuclear binding components. J Biol Chem 253:1065–1073
Jande SS, Maler L, Lawson DEM (1981) Immunohistochemical mapping of vitamin D-dependent calcium-binding protein in brain. Nature 294:765–767
Kim YS, Stumpf WE, Clark SA, Sar M, DeLuca HF (1983) Target cells for 1,25-dihydroxyvitamin D3 in developing rat incisor teeth. J Dent Res 62:58–59
Kim YS, Clark SA, Stumpf WE, DeLuca HF (1985) Nuclear uptake of 1,25-dihydroxyvitamin D3 in developing rodent teeth: an autoradiographic study. Anat Rec 212:301–306
Kream BE, Jose M, Yamada S, DeLuca HF (1977) A specific high-affinity binding macromolecule for 1,25-dihydroxyvitamin D3 in fetal bone. Science 197:1086–1088
Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W (1958) Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 80:2587
Levy FO, Eikvar L, Jute NHPM, Cervenka J, Yoganathan T, Hansson V (1985) Properties and compartmentalization of the testicular receptor for 1,25-dihydroxyvitamin D3. J Steroid Biochem 22:453–460
Loomis WF (1967) Skin-pigment regulation of vitamin-D biosynthesis in man. Science 157:501–506
Lorente F, Fontan G, Para P, Casas C, Garcia-Rodriguez MC, Ojeda JA (1976) Defective neutrophil motility in hypovitaminosis D rickets. Acta Paediatr Scand 65:695–699
Manolagas SC (1985) Role of 1,25 dihydroxyvitamin D3 in the immune system. In: Norman AW, Schaefer K, Grigoleit H-G, Herrath vD (eds) Vitamin D. A chemical, biochemical and clinical update. Walter de Gruyter, Berlin, pp 199–208
Manolagas SC, Taylor CM, Anderson DC (1979) High specific binding of 1,25-dihydroxycholecalciferol in bone cytosol. J Endocrinol 80:35–40
Marche P, Cassier P, Mathieu H (1980) Intestinal calcium-binding protein. Cell Tissue Res 212:63–72
Marx SJ (1984) Resistance to vitamin D. In: Kumar R (ed) Vitamin D. Basic and clinical aspects. Martinus Nijhoff, Boston, pp 721–745
Menaker M (1985) Eyes-the second (and third) pineal glands? In: Evered D, Clark S (eds) Photoperiodism, melatonin and the pineal. Ciba Foundation Symposium 117. Pitman, London, pp 78–87
Merke J, Kreussler W, Bier B, Ritz E (1983) Demonstration and characterization of a testicular receptor for 1,25-dihydroxycholecalciferol in the rat. J Biochem 130:303–308
Narbaitz R, Stumpf WE, Sar M, DeLuca HF, Tanaka Y (1980) Autoradiographic demonstration of target cells for 1,25 dihydroxycholecalciferol in the chick embryo chorioallantoic membrane, duodenum and parathyroid glands. Gen Comp Endocrinol 42:283–289
Narbaitz R, Sar M, Stumpf WE, Huang S, DeLuca HF (1981) 1,25-Dihydroxyvitamin D3 target cells in rat mammary gland. Horm Res 15:263–270
Narbaitz R, Stumpf WE, Sar M, DeLuca HF (1982) The distal nephron in the chick embryo as a target tissue for 1-alpha, 25-dihydroxycholecalciferol. Acta Anatomica 112:208–216
Narbaitz R, Stumpf WE, Sar M, Huang S, DeLuca HF (1983) 1-alpha,25-dihydroxyvitamin D3 in bones from fetal rat. Calcif Tissue Int 35:177–182
Norman AW (1979) Vitamin D. The calcium homeostatic steroid hormone. Academic Press, New York
Norman AW, Frankel BJ, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209:823–825
Norman AW, Roth J, Orci L (1982) The vitamin D endocrine system: steroid metabolism, hormone receptors, and biologial response (calcium binding protein). Endocrine Rev 3:331–366
Ohsugi Y, Nakano T, Komori T, Ueno K, Sugawara Y, Fukushima M, Yamamoto T, Nishii Y, Masuda T, Matsuno M (1985) Effects of 1a-hydroxyvitamin D3 on the immune response. In: Norman AW, Schaefer K, Grigoleit H-G, Herrath vD (eds) Vitamin D. A chemical, biochemical and clinical update. Walter de Gruyter, Berlin, pp 209–218
Pike J, Gooze L, Haussler M (1980) Biochemical evidence for 1,25-dihydroxyvitamin D receptor macromolecules in parathyroid, pancreatic, pituitary and placental tissues. Life Sci 26:407–414
Reiter RJ (1986) The first, the second, and the third pineal gland. Neuroendocrinol Lett 8:1–4
Rose SD, Holick MF (1985) Effects of 1,25-dihydroxyvitamin D3 on the function of rat anterior pituitary cells in primary culture. In: Norman AW, Schaefer K, Grigoleit H-G, Herrath vD (eds) Vitamin D. A chemical, biochemical and clinical update. Walter de Gruyter, Berlin, pp 253–254
Roth J, Thorens B, Hunziger W, Norman AW, Orci L (1981) Vitamin D-dependent Calcium binding protein: immunochemical localization in chick kidney. Science 214:197–199
Sar M, Stumpf WE (1981) Combined autoradiography and immunohistochemistry for simultaneous localization of radioactively labeled steroid hormone and antibodies in the brain. J Histochem Cytochem 29, 1A:201–206
Sar M, Stumpf WE, DeLuca HF (1980) Thyrotropes in the pituitary are target cells for 1,25(OH)2 vitamin D3. Cell Tissue Res 209:161–166
Sar M, Miller WE, Stumpf WE (1981) Effects of 1,25(OH)2 vitamin D3 on thyrotropin secretion in vitamin D deficient male rats. Physiologist 24:70
Sonnenberg J, Luine VN, Krey CR, Christakos S (1986) 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 118:1433–1439
Spanos E, Colston KW, Evans IMS, Galante LS, MacAuley SJ, MacIntyre I (1976) Effects of prolactin on vitamin D metabolism. Mol Cell Endocrinol 5:163–167
Spencer EM, Tobiasson O (1977) The effect of hypophysectomy on 25-hydroxyvitamin D metabolism in the rat. In: Norman AW, Schaefer K, Coburn JW, DeLuca HF, Fraser D, Grigoleit H-G, Herrath vD (eds) Vitamin D: biochemical, chemical, and clinical aspects related to calcium metabolism. Walter de Gruyter, Berlin, p 197
Steenbock H, Herting DC (1955) Vitamin D and growth. J Nutr 57:449–468
Ströder J, Franzen CH (1975) Die unspezifische Entzündungsreaktion bei Vitamin-D-Mangel-Rachitis. Klin Pädiatr 187:461–467
Stumpf WE (1988a) The endocrinology of sunlight and darkness. Complementary roles of vitamin D and pineal hormones. Naturwissenschaften 75:247–251
Stumpf WE (1988b) The first eye; and the second third and fourth eyes. Relationships between skin, pineal and lateral eyes. Neuroendocrinol Lett (in press)
Stumpf WE, Downs TW (1987) Nuclear receptors for 1,25(OH)2 vitamin D3 in thymus reticular cells studied by autoradiography. Histochemistry 87:367–369
Stumpf WE, Jennes L (1984) The A-B-C (Allocortex-Brainstem-Core) circuitry of endocrine-autonomic integration and regulation. Relationships between estradiol sites of action and peptidergic-aminergic neural systems. Peptides 5(Suppl 1):221–226
Stumpf WE, O'Brien LP (1987a) Autoradiographic studies with 3H 1,25 dihydroxyvitamin D3 in thyroid and associated tissues in the neck region. Histochemistry 87:53–58
Stumpf WE, O'Brien LP (1987b) 1,25(OH)2 Vitamin D3 sites of action in the brain: an autoradiographic study. Histochemistry 87:393–406
Stumpf WE, Sar M (1976) Autoradiographic localization of estrogen, androgen, progestin and glucocorticosteroid in “target tissues” and “non-target tissues”. In: Pasqualini J (ed) Receptors and mechanism of action of steroid hormones. Marcel Dekker, New York, pp 41–84
Stumpf WE, Sar M (1981) Anatomical relationships between estrogen target sites and peptidergic-aminergic neurons: Multiple activation of heterogeneous systems (MAHS). Exp Brain Res (Suppl) 3:18–28
Stumpf WE, Sar M, Joshi SG (1974) Estrogen target cells in the skin. Experientia 30:196–198
Stumpf WE, Sar M, Keefer DA, Martinez-Vargas MC (1976) The anatomical substrate of neuroendocrine regulation as defined by autoradiography with 3H-estradiol, 3H-testosterone, 3H-dihydrotestosterone and 3H-progesterone. In: Anand Kumar TC (ed) Neuroendocrine regulation of fertility. Karger, Basel, pp 46–56
Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HF (1979) Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary and parathyroid. Science 206:1188–1190
Stumpf WE, Sar M, Clark SA, Lieth E, DeLuca HF (1980a) Target neurons for 1,25(OH)2 vitamin D3 in brain and spinal cord. Neuroendocrinol Lett 2:297–301
Stumpf WE, Sar M, Narbaitz R, Reid FA, DeLuca HF, Tanaka Y (1980b) Cellular and subcellular localization of 1,25 (OH)2 vitamin D3 in rat kidney: comparison with that of parathyroid hormone and estradiol. Proc Natl Acad Sci USA 77:1149–1153
Stumpf WE, Sar M, DeLuca HF (1981a) Sites of action of 1,25(OH)2 vitamin D3 identified by thaw-mount autoradiography. In: Cohn CV, Talmage RV, Matthews JrVL (eds) Hormonal control of calcium metabolism. Excerpta Medica, Amsterdam, pp 222–229
Stumpf WE, Sar M, Reid FA, Huang S, Narbaitz R, DeLuca HF (1981b) Autoradiographic studies with 3H 1,25(OH)2 vitamin D3 and 3H 25(OH) vitamin D3 in rat parathyroid glands. Cell Tissue Res 221:333–338
Stumpf WE, Sar M, Zuber TJ, Soini E, Tuohimaa P (1981c) Quantitative assessment of steroid hormone binding sites by thawmount autoradiography. J Histochem Cytochem 29(1A):201–206
Stumpf WE, Sar M, Clark SA, DeLuca HF (1982) Brain target sites for 1,25-dihydroxyvitamin D3. Science 215:1404–1405
Stumpf WE, Gasc JM, Baulieu EE (1983a) Progestin receptors in pituitary and brain: combined autoradiography-immunohis-tochemistry with tritium-labeled ligand and receptor antibodies. Mikroskopie 40:359–363
Stumpf WE, Sar M, Narbaitz R, Huang S, DeLuca HF (1983b) Autoradiographic localization of 1,25-dihydroxyvitamin D3 in rat rat placenta and yolk sac. Horm Res 18:215–220
Stumpf WE, Clark SA, Sar M, DeLuca HF (1984) Topographical and developmental studies on 1,25(OH)2 vitamin D3 target sites in skin. Cell Tissue Res 238:489–496
Stumpf WE, Clark SA, Kim YS, DeLuca HF (1985) Comparison of cellular and subcellular distribution of vitamin D metabolites [1,25(OH)2 vitamin D3, 24,25(OH)2 vitamin D3, 25(OH) vitamin D3] in target tissues. In: Norman AW, Schaefer K, Grigoleit HG, Herrath vD (eds) Vitamin D: a biochemical and clinical update. Walter de Gruyter, Berlin, pp 119–120
Stumpf WE, Sar M, O'Brien LP (1987a) Vitamin D sites of action in the pituitary studied by combined autoradiography-immunohistochemistry. Histochemistry 88:11–16
Stumpf WE, Sar M, Chen K, Morin J, DeLuca HF (1987b) Sertoli cells in the testis and epithelium of the ductuli efferentes are targets for 3H 1,25(OH)2 vitamin D3: an autoradiographic study. Cell Tissue Res 247:453–455
Stumpf WE, O'Brien LP, Clark SA, Reid FA (1988a) 1,25(OH)2 Vitamin D3 sites of action in spinal cord and sensory ganglion. Anat Embryol 177:307–310
Stumpf WE, Sar M, O'Brien LP, Morin J (1988b) Pyloric gastrinproducing cells and pyloric sphincter muscle cells are nuclear targets for 3H 1,25(OH)2 vitamin D3. Studied by autoradiography and immunohistochemistry. Histochemistry (in press)
Tanaka Y, Castillo L, DeLuca HF (1976) Control of renal vitamin D hydroxylase in birds by sex hormones. Proc Natl Acad Sci USA 73:2701–2705
Tomita Y, Fukushima M, Tagami H (1986) Stimulation of melanogenesis by cholecalciferol in cultured human melanocytes: a possible mechanism underlying pigmentation after ultraviolet irradiation. Tohoku J Exp Med 149:451–452
Törnquist K, Lamberg-Allardt C (1985) Effects of 1,25(OH)2D3, Verapamil and EDTA-infusion on the thyroliberin-induced thyrotropin release. In: Norman AW, Schaefer K, Grigoleit HG, Herrath vD (eds) Vitamin D. A chemical, biochemical and clinical update. Walter de Gruyter, Berlin, pp 363–364
Walters MR (1981) An estrogen-stimulated 1,25-dihydroxyvitamin D3 receptor in rat uterus. Biochem Biophys Res Commun 103:721–726
Walters MR, Cuneo DL, Jamison AP (1983) Possible significance of new target tissues for 1,25-dihydroxyvitamin D3. J Steroid Biochem 19:913–920
Walters MR, Wicker DC, Riggle PC (1986) 1,25-Dihydroxyvitamin D3 receptors identified in the rat heart. J Mol Cell Cardiol 18:67–72
Weber JC, Pons V, Kodicek E (1971) The localization of 1,25-dihydroxycholecalciferol in bone cell nucleic of rachitic chicks. Biochem J 125:147–153
Wecksler WR, Henry HL, Norman AW (1977) Studies on the mode of action of calciferol. Subcellular localization of 1,25-dihydroxyvitamin D3 in chicken parathyroid glands. Arch Biochem Biophys 183:168–175
Wehr TA, Jacobsen FM, Sack DA, Arendt J, Tamarkin L, Rosenthal NE (1986) Phototherapy of seasonal affective disorder. Arch Gen Psychiatry 43:870–875
Wills L, Sanderson P, Paterson D (1926) Calcium absorption in relation to gastric acidity (A study of rickets). Arch Dis Child 1:245–254
Yetgin S, Ozsoylu S (1982) Myeloid metaplasia in vitamin D deficiency rickets. Scand J Haematol 28:180–185
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stumpf, W.E. Vitamin D — Soltriol The heliogenic steroid hormone: Somatotrophic activator and modulator. Histochemistry 89, 209–219 (1988). https://doi.org/10.1007/BF00493142
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00493142