Anatomy and Embryology

, Volume 193, Issue 2, pp 145–160 | Cite as

Vitamin D target systems in the brain of the green lizard Anolis carolinensis

  • Hans-Jürgen Bidmon
  • Walter E. Stumpf
Original Article


Autoradiographic mapping criteria were employed to identify and localize specific high affinity binding sites (receptors) for the steroid hormone 1,25-dihydroxyvitamin D3 (1,25-D3) in the brain of Anolis carolinensis. In female and male lizards binding of tritiated 1,25-D3 occurred in identical regions of the fore-, mid-, and hindbrain, similar to findings in other species. There was a band of intensely labeled neurons forming a continuum from the n. accumbens, n. striae terminalis, the striatum, and extending into the amygdala. Target areas with high to intermediate labeling intensities were present in many other regions of the brain and single, small target cells were found throughout the organ. Some cells in the pituitary and pineal were labeled and also cells associated with the meninges, choroid plexuses and ependyma. The differential labeling suggests the existence of different 1,25-D3-responsive systems. One of the conspicuous “high capacity-high affinity systems” is found in the n. accumbens-n. striae terminalis and the amygdala. Most of the cerebral target regions for vitamin D correspond to those known for gonadal steroids, and the seasonal steroid 1,25-D3 may therefore act in conjunction with gonadal steroids in this seasonally breeding reptile.

Key words

Vitamin D receptor Central nervous system Choroid plexus Meninges Reptile 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ariens Kappers CU, Huber GC, Crosby EC (1967) The comparative anatomy of the nervous system of vertebrates, including man, vol 2. Hafner, New YorkGoogle Scholar
  2. Baksi SN, Hughes MJ (1982) Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Res 242: 387–396Google Scholar
  3. Balabanova S, Richter H-P, Antoniadis G, Homoki J, Kremmer N, Hanle J, Teller WM (1984) 25-Hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in human cerebrospinal fluid. Klin Wochenschr 62: 1086–1090Google Scholar
  4. Bell, RA, Joachim FG (1976) Techniques for rearing laboratory colonies of tobacco hornworms and pink bollworms. Ann Entomol Soc Am 69: 365–373Google Scholar
  5. Bernard JB, Ofiedal OT, Barboza PS, Mathias CE, Allen ME, Citino SB, Ullrey DE, Montali RJ (1991) The response of vitamin D-deficient green Iguanas (Iguana iguana) to artificial ultraviolet light. Proc Am Assoc Zoo Vet 3: 147–150Google Scholar
  6. Bidmon HJ (1995) 1,25-Dihydroxyvitamin D3 rezeptive Organe in Amphibien und Reptilien: Hinweise auf multiple endokrine und neuroendokrine Funktionen von Vitamin D. Protocols of the 5th Workshop on Diseases of amphibians and reptiles. Deutsche Gesellschaft für Herpetologie und Terrarienkunde (DGHT), DGHT-Schriftensammlung, Rheinbach, pp 1–9Google Scholar
  7. Bidmon HJ, Sliter TJ (1990) The ecdysteroid receptor. Int J Invert Reprod Dev 18: 13–27Google Scholar
  8. Bidmon HJ, Stumpf WE (1991) Phylogeny of receptors for 1,25-dihydroxyvitamin D3 (soltriol) in vertebrates and invertebrates. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D gene regulation, structure-function, analogies, and clinical application. de Gruyter, Berlin, pp 673–674Google Scholar
  9. Bidmon HJ, Stumpf WE (1992) Choroid plexus, ependyma and arachnoidea express receptors for vitamin D: differences between seasonal and non-seasonal breeders. Prog Brain Res 91: 279–283Google Scholar
  10. Bidmon HJ, Stumpf WE (1994a) Distribution of the nuclear receptor for vitamin D in female and male zebra finches, Taeniopygia guttata. Cell Tissue Res 276: 333–345Google Scholar
  11. Bidmon HJ, Stumpf WE (1994b) Distribution of target cells for 1,25-dihydroxyvitamin D3 in the brain of the yellow bellied turtle Trachemys scripta. Brain Res 640: 277–285Google Scholar
  12. Bidmon HJ, Stumpf WE (1995) 1,25-Dihydroxyvitamin D3binding in the eye and associated tissues of the green lizard Anolis carolinensis. Histochem J 27: 516–523Google Scholar
  13. Bidmon HJ, Mayerhofer A, Heiss C, Bartke A, Stumpf WE (1991) Vitamin D (soltriol) receptors in choroid plexus and ependyma: their species-specific presence. Mol Cell Neurosci 2: 145–156Google Scholar
  14. Bikle DD (1992) Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential. Endocr Rev 13: 765–784Google Scholar
  15. Bikle DD, Pillai S (1993) Vitamin D, calcium, and epidermal differentiation. Endocr Rev 14: 3–19Google Scholar
  16. Clemens TL, Garrett KP, Zhou X-Y, Pike JW, Haussler MR, Dempster DW (1988) Immunocytochemical localization of the 1,25-dihydroxyvitamin D3 receptor in target cells. Endocrinology 122: 1224–1230Google Scholar
  17. Crews D, Rosenblatt JS, Lehrmann DS (1974) Effects of unseasonal environmental regime, group presence, group composition and males' physiological state on ovarian recrudescence in the lizard, Anolis carolinensis. Endocrinology 94: 541–547Google Scholar
  18. Czarnetzki BM (1989) Vitamin D3 in dermatology: a critical appraisal. Dermatologica 178: 184–188Google Scholar
  19. Desan PH, Lopez KH, Austin HB, Jones RE (1992) Asymmetric metabolism of hypothalamic catecholamines alternates with side of ovulation in a lizard (Anolis carolinensis). J Exp Zool 262: 105–112Google Scholar
  20. De Viragh PA, Wolfer D, Lipp HA, Celio MR (1988) Behavioral changes in chronically D-hyper-vitaminotic animals. In: Norman AW, Schaefer K, Grigoleit HG, Herrath D von (eds) Vitamin D. Molecular, cellular and clinical endocrinology, de Gruyter, Berlin, pp 1001–1006Google Scholar
  21. De Viragh PA, Haglid KG, Celio MR (1989) Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis. Proc Natl Acad Sci USA 86: 3887–3890Google Scholar
  22. Evans RM (1988) The steroid and thyroid hormone superfamily. Science 240: 889–895Google Scholar
  23. Fink G (1994) Molecular principles from neuroendocrine models: steroid control of central neurotransmission. Progr Brain Res 100: 139–147Google Scholar
  24. Greenberg N (1977) A neuroethological study of display behavior in the lizard, Anolis carolinensis (Reptilia, Lacertilia, Iguanidae). Am Zool 17: 177–191Google Scholar
  25. Greenberg N (1982) A forebrain atlas and stereotaxic technique for the lizard, Anolis carolinensis. J Morphol 174: 217–236Google Scholar
  26. Greenberg N (1993) Central and endocrine aspects of tongueflicking and exploratory behavior in Anolis carolinensis. Brain Behav Evol 41: 210–218Google Scholar
  27. Greenberg N, Crews D (1991) Endocrine and behavioral responses to aggression and social dominance in the green anole lizard, Anolis carolinensis. Gen Comp Endocrinol 77: 246–255Google Scholar
  28. Greenberg N, MacLean PD, Ferguson JL (1979) Role of the paleostriatum in species-typical display behavior of the lizard (Anolis carolinensis). Brain Res 172: 229–241Google Scholar
  29. Greenberg N, Burghardt GM, Crews D, Font E, Jones RE, Vaughan G (1989) Reptile models for biomedical research. In: Woodhead AD, Vivirito K (eds) Nonmammalian animal models for biomedical research. CRC, Boca Raton, Fl., pp 289–308Google Scholar
  30. Henselmans JML, Hoogland PV, Stoof JC (1991) Differences in the regulation of acetylcholine release upon D2 dopamine and N-methyl-D-aspartate receptor activation between the striatal complex of reptiles and the neostriatum of rats. Brain Res 506: 8–12Google Scholar
  31. Holick MF (1991) Vitamin D. Cutaneous production and therapeutic efficacy in psoriasis. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D gene regulation, structure-function, analogies, and clinical application. de Gruyter, Berlin, pp 940–948Google Scholar
  32. Holick MF, Tian XQ, Allen M (1995) Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals. Proc Natl Acad Sci USA 92: 3124–3126Google Scholar
  33. Isenberg KE, Ukhan IA, Holstad SG, Jafri S, Uchida U, Zormunski CF, Yang J (1993) Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit. Neuroreport 5: 121–124Google Scholar
  34. Johnson JA, Grande JP, Roche PC, Campbell RJ, Kumar R (1995) Immuno-localization of the calcitriol receptor, calbindin-D28k and the plasma membrane calcium pump in the human eye. Curr Eye Res 14: 101–108Google Scholar
  35. Jones RE, Desan PH, Lopez KH, Austin HB (1989) Asymmetry in diencephalic monoamine metabolism is related to side of ovulation in a reptile. Brain Res 453: 185–191Google Scholar
  36. Kaji H, Hinkle PM (1989) Attenuation of thyroid hormone action by 1,25-dihydroxyvitamin D3 in pituitary cells. Endocrinology 124: 930–936Google Scholar
  37. Khachaturian H, Dores RM, Watson SJ, Akil H (1984) β-Endorphin/ACTH immunocytochemistry in CNS of the lizard Anolis carolinensis: evidence for a major mesencephalic cell group. J Comp Neurol 229: 576–584Google Scholar
  38. Kim YS, Stumpf WE, Sar M, Martinez-Vargas MC (1978) Estrogen and androgen target cells in the brain of fishes, reptiles, and birds: phylogeny and ontogeny. Am Zool 18: 425–433Google Scholar
  39. Lauber AH, Romano GL, Pfaff DW (1991) Sex differences in estradiol regulation of progestin receptor mRNA in rat mediobasal hypothalamus as demonstrated by in situ hybridization. Neuroendocrinology 53: 608–613Google Scholar
  40. Licht P (1967) Environmental control of annual testicular cycles in the lizard Anolis carolinensis. II. Seasonal variations in the effects of photoperiod and temperature on testicular recrudescence. J Exp Zool 166: 242–254Google Scholar
  41. Lopez KH, Jones RE, Seufert DW, Rand MS, Dores RM (1992) Catecholaminergic cells and fibers in the brain of the lizard Anolis carolinensis identified by traditional as well as wholemount immunohistochemistry. Cell Tissue Res 270: 319–337Google Scholar
  42. Martinez-Garcia F, Olucha FE, Teruel V, Lorente MJ, Schwerdtfeger WK (1991) Afferent and efferent connections of the olfactory bulbs in the lizard Podarcis hispanica. J Comp Neurol 305: 337–347Google Scholar
  43. Martinez-Vargas MC, Keefer DA, Stumpf WE (1978) Estrogen localization in the brain of the lizard, Anolis carolinensis. J Exp Zool 205: 141–147Google Scholar
  44. Minghetti PP, Norman AW (1988) 1,25(OH)2-vitamin D3 receptors: gene regulation and genetic circuitry. FASEB J 2: 3043–3053Google Scholar
  45. Morrell JI, Crews, D, Ballin A, Morgentaler A, Pfaff DW (1979) 3H-Estradiol, 3H-testosterone and 3H-dihydrotestosterone localization in brain of the lizard Anolis carolinensis: an autoradiographic study. J Comp Neurol 188: 201–224Google Scholar
  46. Musiol IM, Stumpf WE, Bidmon HJ, Mayerhofer A, Heiss C, Bartke A (1992) Vitamin D nuclear binding to neurons of septal substriatal and amygdaloid area in the Siberian hamster. Neuroscience 48: 841–848Google Scholar
  47. Naik DR, Sar M, Stumpf WE (1981) Immunohistochemical localization of enkephalin in the central nervous system and pituitary of lizards, Anolis carolinensis. J Comp Neurol 198: 583–601Google Scholar
  48. Naveilhan P, Berger F, Haddad K, Barbot N, Benabid AL, Brachet P, Wion D (1994) Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine therapy of brain tumors? J Neurosci Res 37: 271–277Google Scholar
  49. Neveu I, Naveilhan P, Baudet C, Brachet P, Metsis M (1994) 1,25-Dihydroxy-vitamin D3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 6: 124–126Google Scholar
  50. Norman AW, Nemere I, Zhou LX, Bishop JE, Lowe KE, Maiyar AC, Collins ED, Taoka T, Sergeev I, Farbach-Carson MC (1992) 1,25(OH)2-Vitamin D3, a steroid hormone that produces biological effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol 41: 231–240CrossRefPubMedGoogle Scholar
  51. Nürnberger F, Lee TF, Jourdan ML, Wang LCH (1991) Seasonal changes in methionine-enkephalin immunoreactivity in the brain of a hibernator, Spermophilus columbianus. Brain Res 547: 115–121Google Scholar
  52. Nürnberger F, Lee TF, Staiger JF, Wang LCH (1994) Involvement of limbic-neuroendocrine interactions in control of hibernation. In: Pleschka K, Gerstberger R (eds) Integrative and cellular aspects of autonomic functions: temperature and osmoregulation. John Libbey Eurotext, Paris, pp 259–268Google Scholar
  53. Pneunova N, Enikolopov G (1995) Nitric oxide triggers a switch to growth arrest during differentiation of neuronal cells. Nature 375: 68–73Google Scholar
  54. Privette TH, Stumpf WE, Mueller RA, Hollis, BW (1991) Serum 1,25-dihydroxyvitamin D3 (soltriol) levels influence serotonin levels in the hypothalamus of the rat. Abstr Soc Neurosci 17: 981Google Scholar
  55. Propper CR, Jones RE, Lopez KH (1992a) Distribution of arginine vasotocin in the brain of the lizard Anolis carolinensis. Cell Tissue Res 267: 391–398Google Scholar
  56. Propper CR, Jones RE, Dores RM, Lopez KH (1992b) Arginin vasotocin concentration in the supraoptic nucleus of lizard Anolis carolinensis are associated with reproductive state but not oviposition. J Exp Zool 264: 461–467Google Scholar
  57. Provencio I, Foster RG (1993) Vitamin A2-based photopigments within the pineal gland of a fully terrestrial vertebrate. Neurosci Lett 155: 223–226Google Scholar
  58. Puchacz E, Goc A, Stumpf WE, Bidmon HJ, Stachowiak EK, Stachowiak MR (1991) Vitamin D regulates expression of tyrosine hydroxylase gene in adrenal chromaffin cells. Abstr Neurosci 17: 981Google Scholar
  59. Rivkees SA, Carlson LL, Reppert SM (1989) Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain. Proc Natl Acad Sci USA 86: 3882–3886Google Scholar
  60. Sachs BD, Meisel RL (1988) The physiology of sexual behavior. In: Knobil E, Neil J (eds) The physiology of reproduction. Raven Press, New York, pp 1393–1487Google Scholar
  61. Sar M, Stumpf WE, DeLuca HF (1980) Thyrotrops in the pituitary are target cells for 1,25 (OH)2 vitamin D3. Cell Tissue Res 209: 161–166Google Scholar
  62. 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: 70Google Scholar
  63. Shaw AP, Collazo CR, Easterling K, Young CD, Karwoski CJ (1993) Circadian rhythm in the visual system of the lizard Anolis carolinensis. J Biol Rhythms 8: 107–124Google Scholar
  64. Siegel A, Malkowitz L, Moskovits MJ, Christakos S (1984) Administration of 1,25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats. Brain Res 298: 125–131Google Scholar
  65. Sonnenberg J, Luine VN, Krey LC, Christakos S (1986) 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 118: 1433–1439Google Scholar
  66. Stumpf WE (1988) Vitamin D-soltriol, the heliogenic steroid hormone: somatotrophic activator and modulator. Histochemistry 89: 209–219Google Scholar
  67. Stumpf WE, Bidmon H-J (1990) Vitamin D3 receptors and their organ-specific distribution in lower vertebrates (Pisces, Amphibia, Reptilia). Verh Dtsch Zool Ges 83: 591–592Google Scholar
  68. Stumpf WE, Denny ME (1989) Vitamin D (soltriol), light, and reproduction. Am J Obstet Gynecol 161: 1375–1384Google Scholar
  69. Stumpf WE, O'Brien LP (1987a) 1,25(OH)2 vitamin D3 sites of action in brain. Histochemistry 87: 393–406Google Scholar
  70. Stumpf WE, O'Brien LP (1987b) Autoradiographic studies with 3H 1,25-dihydroxyvitamin D3 in thyroid and associated tissues of the neck region. Histochemistry 87: 53–58Google Scholar
  71. Stumpf WE, Privette TH (1989) Light, vitamin D and psychiatry. Psychopharmacology 97: 285–294Google Scholar
  72. Stumpf WE, Privette TH (1991) The steroid hormone of sunlight soltriol (vitamin D) as a seasonal regulator of biological activities and photoperiodic rhythms. J Steroid Biochem Mol Biol 39: 283–289Google Scholar
  73. Stumpf, WE, Sar M, Lieth E, DeLuca HF (1980) Target neurons for 1,25 (OH)2 vitamin D3 in brain and spinal cord. Neuroendocrinol Lett 2: 297–301Google Scholar
  74. Stumpf WE, Sar M, Clark SA, DeLuca HF (1982) Brain target sites for 1,25-dihydroxyvitamin D3. Science 215: 309–312Google Scholar
  75. Stumpf WE, Shughrue PJ, Duncan GE (1991) The use of autoradiography for regional and cellular subcellular localization of radiolabeled substances in central nervous system. In: Greenstein BD (ed) Neuroendocrine research methods. Harwood, Reading, UK, pp 631–651Google Scholar
  76. Stumpf WE, Bidmon H-J, Li L, Pilgrim C, Bartke A, Mayerhofer A, Heiss C (1992) Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain of Siberian hamster (Phodopus sungorus) assessed by autoradiography. Histochemistry 98: 155–164Google Scholar
  77. Sutherland MK, Sommerville MJ, Yoong LK, Bergerson C, Haussler MR, McLachlan DR (1992) Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels. Mol Brain Res 13: 239–250Google Scholar
  78. Tian XQ, Chen TC, Allen M, Holick MF (1994) Photosynthesis of previtamin D3 and its isomerization to vitamin D3 in the Savanna monitor lizard. In: Norman AW, Bouillion R, Thomasset M (eds) Vitamin D, a pluripotent steroid hormone, de Gruyter, Berlin, pp 893–894Google Scholar
  79. Tokarz RR, Crews D (1981) Effects of prostaglandins on sexual receptivity in the female lizard Anolis carolinensis. Endocrinology 109: 451–457Google Scholar
  80. Tokarz RR, Crews D, McEwen BS (1981) Estrogen sensitive progestin binding sites in the brain of lizard, Anolis carolinensis. Brain Res 220: 95–105Google Scholar
  81. Ulinski, PS (1983) Dorsal ventricular ridge. A treatise on forebrain organization in reptiles and birds. Wiley, New YorkGoogle Scholar
  82. Ullrey DE, Bernard JB, Allen ME (1992) Nutritional considerations in feeding reptiles (calcium and vitamin D) (abstract). Proc Int Herpetological Symposium, St. Louis, Mo., USA, pp 8–9Google Scholar
  83. Underwood H (1985) Pineal melatonin rhythms in lizard Anolis carolinensis: effects of light and temperature cycles. J Comp Physiol [A] 157: 57–65Google Scholar
  84. Underwood H, Calaban M (1987) Pineal melatonin rhythms in lizard Anolis carolinensis. I. response to light and temperature cycles. J Biol Rhythms 2: 179–193Google Scholar
  85. Underwood H, Gross G (1982) Vertebrate circadian rhythms: retinal and extraretinal photoreception. Experientia 38: 1013–1021Google Scholar
  86. Underwood H, Harless M (1985) Entrainment of circadian activity rhythm of lizard to melatonin injections. Physiol Behav 35: 267–270Google Scholar
  87. Walters MR (1992) Newly identified actions of vitamin D endocrine system. Endocrinol Rev 13: 719–764Google Scholar
  88. Watts AG (1991) The efferent projections of the suprachiasmatic nucleus: anatomical insights into the control of circadian rhythms. In: Klein DC, Moore RY, Reppert SM (eds) Suprachiasmatic nucleus; the mind's clock. Oxford University Press, Oxford New York, pp 77–106Google Scholar
  89. Wheeler JM, Crews D (1978) The role of the anterior hypothalamus-preoptic area in the regulation of male reproductive behavior in the lizard, Anolis carolinensis: lesion studies. Horm Behav 11: 42–60Google Scholar
  90. Wiechmann AF, Wirsig-Wiechmann CR (1992) Asymmetric distribution of melatonin receptors in the brain of the lizard Anolis carolinensis. Brain Res 593: 281–286Google Scholar
  91. Wion D, MacGrogan D, Neveu I, Jehan F, Houlgatte R, Brachet P (1991) 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. J Neurosci Res 28: 110–114Google Scholar
  92. Young LR, Lopreato GF, Horan K, Crews D (1994) Cloning and in situ hybridization analysis of estrogen receptor, progesterone receptor, and androgen receptor expression in the brain of whiptail lizards (Cnemidophorus uniparens and C. inornatus). J Comp Neurol 347: 288–300Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Hans-Jürgen Bidmon
    • 1
  • Walter E. Stumpf
    • 2
  1. 1.Institute of Neuroanatomy, Heinrich Heine UniversityDüsseldorfGermany
  2. 2.Department of Cell Biology and AnatomyUniversity of North CarolinaChapel HillUSA

Personalised recommendations