Vitamin D target tissues

Vitamin D target tissues and cells discovered and characterized with high resolution Receptor Microscopic Autoradiography (Laboratory Dr. Walter E. Stumpf). References listed chronologically.

Starting in 1979, vitamin D target cell populations have been demonstrated throughout the body in specific locations with functions that go far beyond systemic calcium regulation. Insights derived from these ‘ubiquitous’ targets and related functions led to a change of concept of the main functions of the sunshine hormone 1,25(OH)2 vitamin D3-soltriol (refs. 38, 100):

Regulation of vital functions and adaptation to seasonal changes through genomic effects on specific cell proliferation and differentiation and exo- and endocrine secretion, broadly related to growth and survival, fertility and reproduction, maintenance and restitution.  

This wide spectrum of actions involves many organs, including the pituitary and brain-spinal cord (neuro-endocrine, neuro-sensory, neuro-muscular, cognitive), thyroid-parathyroid, pancreas, adrenal, skin and its appendices; as well as the digestive, cardio-vascular, skeletal, renal, lymphatic, hemato-poetic, female and male reproductive systems.

Nuclear uptake and retention (specific binding) of 1,25(OH)2 vitamin D3 (soltriol) varies quantitatively among target tissues, indicating a nuclear receptor binding hierarchy and related modulation of effects, variable with age and other conditions (to be further studied). Such properties can be conveniently reviewed in a DRUG HOMUNCULUS (ref. 97, 98), with links to function. Thus, the topological and quantitative information provides a basis for comparisons of target kinetics and development of systems theory of drug-hormone actions.

Most of the currently known vitamin D target tissues have been discovered and characterized in rats, mice, hamsters and representatives of vertebrate phyla (birds, reptiles, amphibia, fish) with the histochemical method specifically developed in our laboratories for the tissue and cellular localization of hormones and drugs (www.walterstumpf.com).  
In our experiments no supportive evidence has been obtained for plasma membrane association of 1,25(OH)2 vitamin D3 – claimed in some studies reported in the literature. In pilot studies with 24,25(OH)2 vitamin D3 no indication existed for nuclear binding.

Several of the discovered 1,25(OH)2 vitamin D3 targets remain to be further studied as to the specific hormonal effects. These targets include: stomach isthmus cells, entero-endocrine cells, pyloric muscle cells; parotid and other salivary gland cells, teeth pulp cells, thymus reticular cells, oral and esophageal surface epithelium; spinal cord motor and sensory neurons, cranial motor neurons, various forebrain, midbrain and hindbrain neurons (maps published; Refs. 5, 12, 18, 34, 36, 51, 53, 55, 59, 60, 61, 63, 64, 72), adrenal medullary cells, kidney macula densa cells and podocytes, liver Ito cells (cytoplasmic retention), female and male reproductive organs, atrial cardio-myocytes, others.

The histochemical data document, results from biochemical and in vitro methods, from low-resolution imaging, are incomplete, even misleading. Verification and complementation with high-resolution data are necessary as has been demonstrated in comparative studies with vitamin D (Memo to the FDA; ref. 103).

During the 1980s and early 1990s, research of targets of vitamin D unrelated to calcium metabolism was hindered through negative (Ca-biased) anonymous ‘peer’ reviews. For successful acceptance, research proposals and journal articles had to contain connections to calcium or calcium-binding protein. However, we found no general association between sites of vitamin D receptor binding and those with calcium-binding protein and were unable to support the prevailing notion that antibodies to calcium-binding protein can be used as a guide for identifying sites of vitamin D action. Furthermore, our autoradiograms showed that vitamin D-specific binding in newly discovered non-classical target tissues was as strong as or stronger than binding in classical target tissues. Calcium-dependent tissues, like skeletal and smooth muscle, did not display the expected nuclear uptake and concentration of 1,25(OH)2 vitamin D3 (in contrast to positive pyloric muscle cells and atrial cardio-myocytes). Funding of eight distinct research applications to the NSF and NIH Endocrine Study Section was denied, and research in this area had to be terminated in our laboratory.

A 1995 review (ref.77) listed over 50 target tissues for vitamin D, characterized histochemically. After our discoveries of these unexpected sites of vitamin D action - published already during the 1980s - there was a follow-up gap of two decades. Even in 2009 there is still a need to pursue early demonstrated sites of action. Only a few investigators followed with the creation of a ‘vitamin D endocrine system’ for regulating calcium metabolism. Slowly arising from the Prokrustean calcium bed and realizing wide sun light life benefits, some investigators now are proposing vitamin D receptor expression to exist in all cells. But here, too, this opposite and generalizing view appears incorrect if the published evidence below for specific patterns of receptor binding for vitamin D is considered and compared to specific patterns reported for other steroid hormones, like estradiol, testosterone, dihydrotestosterone, corticosterone, aldosterone, ecdysteroids, - which we documented earlier. The topographical and functional links among steroids, cooperative or antagonistic, are another important topic of research – albeit again requiring detailed and at once integrative high-resolution in vivo information through adequate methods.

In 2009, the majority of vitamin D publications is still calcium related – for almost a century now, even though target tissue data and supportive functional-clinical evidence have revealed that calcium regulation is just one of the many important functions of vitamin D. A holistic view and realistic assessment of unexpected (unorthodox) data point to more: A reasonable guide for advances of research and potential drug development of this uniquely salubrious sun-derived hormone – a near ‘panacea’ at the right doses in the right places.

1     Stumpf, WE, Sar, M, Reid, FA, Tanaka, Y and DeLuca, HF (1979)
Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary and parathyroid. SCIENCE 206:1188-1190.

2     Stumpf, WE, Sar, M, Narbaitz, R, Reid, FA, DeLuca, HF and  Tanaka, Y (1980) 
Cellular and subcellular localization of 1,25 (OH)2 vitamin D3 in rat kidney: Comparison with localization of parathyroid hormone and estradiol. PROC NATL ACAD SCI USA 77:1149-1153.

3     Sar, M, Stumpf, WE and DeLuca, HF (1980)
Thyrotropes in the pituitary are target cells for 1,25 (OH)2 vitamin D3. CELL TISS RES 209:161-166.

4     Narbaitz, R, Stumpf, WE, Sar, M, DeLuca, HF and 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.

5     Stumpf, WE, Sar, M, Clark, SA, Lieth, E and DeLuca, HF (1980) 
Target neurons for 1,25 (OH)2 vitamin D3 in brain and spinal cord.  NEUROENDOCRIN LETT 2:297-301.

6     Esvelt, RP, DeLuca, HF, Wichmann, JK, Yoshizawa, S, Zurcher, J, Sar, M and Stumpf, WE (1980)
1,25-dihydroxyvitamin D3 stimulated increase  of 7,8-didehydrocholesterol levels in rat skin.  BIOCHEMISTRY 19:6158-6161.

7     Clark, SA, Stumpf, WE, Sar, M, DeLuca, HF and Tanaka, Y (1980) 
Target cells for 1,25 dihydroxyvitamin D3 in the pancreas. CELL TISS RES 209:515-520.

8     Narbaitz, R, Stumpf, WE and Sar, M (1981)
The role of autoradiographic and immunocytochemical techniques in the clarification of sites of metabolism and action of vitamin D. J HISTOCHEM CYTOCHEM 29:91-100.

9     Stumpf, WE, Sar, M and DeLuca, HF (1981)
Sites of action of 1,25(OH)2 vitamin D3 identified by thaw-mount autoradiography. In: HORMONAL CONTROL OF CALCIUM METABOLISM,DV Cohn, RV Talmage and JL Matthew, Jr., eds., pp. 222-229, EXCERPTA MEDICA, Amsterdam.

10    Sar, M, Miller, WL and Stumpf, WE (1981)
Effects of 1,25 (OH)2 vitamin D3 on thyrotropin secretion in vitamin D deficient male rats. (Abstract) PHYSIOLOGIST 24:70.

11    Clark, SA, Stumpf, WE and Sar, M (1981)
Effects of 1,25 dihydroxyvitamin D3 on insulin secretion. DIABETES 30:382-386.

12    Stumpf, WE and Sar, M (1981)
Steroid hormone sites of action in the brain. In: STEROID HORMONE REGULATION OF THE BRAIN. K Fuxe, J-A Gustafsson and L Wetterberg, eds., pp. 41-50, Pergamon Press, New York.

13    Chertow, BS, Clark, SA, Baranetsky, NG, Sivitz, WI, Stumpf, WE and Waite, AT (1981)
Effects of 1,25 dihydroxycholecalciferol (1,25(OH)2 D3) on insulin secretion from isolated rat islets. CLIN RES 29:402A.

14    Clark, SA, Chertow, BS, Baranetsky, NG, Sivitx, WI, Stumpf, WE and Waite, AT (1981)
Effects of vitamin D deficiency on insulin secretion in the rat. (Abstract) DIABETES 30(S1):123A.

15    Stumpf, WE, Sar, M, Reid, FA, Huang, S, Narbaitz, R and DeLuca, HF (1981) 
Autoradiographic studies with 3H 1,25 (OH)2 vitamin D3 and 3H 25 (OH) vitamin D3 in rat parathyroid glands. CELL TISS RES 221:333-338.

16    Narbaitz, R, Sar, M, Stumpf, WE, Huang, S and DeLuca, HF (1981)   
1,25-Dihydroxyvitamin D3 target cells in rat mammary gland. HORM RES 15:263-270.

17    Narbaitz, R, Sar, M, Stumpf, WE, and DeLuca, HF (1982)
The distal nephron in the chick embryo as a target tissue for 1-alpha,25-dihydroxycholecalciferol. ACTA ANATOMICA 112:208-216.

18    Stumpf, WE, Sar, M, Clark, SA and DeLuca, HF (1982)
Brain target sites for 1,25-dihydroxyvitamin D3. SCIENCE 215:1403-1405.

19    Kim, YS, Stumpf, WE, Clark, SA, Sar, M and DeLuca, HF (1983)
Target cells for 1,25-dihydroxyvitamin D3 in developing rat incisor teeth. J DENT RES 62:58-59.

20    Narbaitz, R, Stumpf, WE, Sar, M, Huang, S and DeLuca, HF (1983)          
Autoradiographic localization of target cells for 1-alpha,25-dihydroxyvitamin D3 in bones from fetal rat. CALCIF TISS INT 35:177-182.

21    Stumpf, WE, Sar, M, Narbaitz, R, Huang, S and DeLuca, HF (1983)    
Autoradiographic localization of 1,25-dihydroxyvitamin D3 in rat placenta and yolk sac. HORM RES 18:215-220.

22    Stumpf, WE, Clark, SA, Sar, M and DeLuca, HF (1984)
Topographical and developmental studies on target sites of 1,25 (OH)2 vitamin D3 in skin. CELL TISS RES 238: 489-496. 

23    Kim, YS, Clark, SA, Stumpf, WE and DeLuca HF (1985)
Nuclear uptake of 1,25-dihydroxyvitamin D3 in developing rodent   teeth: An autoradiographic study. ANAT REC 212:301-306.

24    Clark, SA, Dame, MC, Kim, YS, Stumpf, WE and DeLuca, HF (1985)    
1,25-Dihydroxyvitamin D3 in teeth of rats and humans: Receptors and nuclear localization. ANAT REC 212:250-254.

25    Clark, SA, Stumpf, WE, Bishop, CW, DeLuca, HF, Park, DH and Joh, TH (1985)
Identification and developmental appearance of calcitriol (1,25-vitamin D3) target cells and cells with vitamin D-dependent calcium-binding protein in the adrenal.(Abstract) ANAT REC 211:42A.

26    Clark, SA, Toverud, SV, Narbaitz, R and Stumpf, WE (1985)
Selective effects of vitamin D deficiency on carbohydrate  homeostasis. (Abstract) DIABETES 34:709. 

27    Stumpf, WE, Clark, SA, Kim, YS, and 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: VITAMIN D: A BIOCHEMICAL AND CLINICAL UPDATE, AW Norman, K Schaefer, HG Grigoleit and DV Herrath, eds., Walter de Gruyter, Berlin, pp. 119-120.

28    Clark, SA, Stumpf, WE, Bishop, CW, DeLuca, HF, Park, DH and Joh, TH (1986)
The adrenal: A new target organ of the calciotropic hormone 1,25-dihydroxyvitamin D3. CELL TISS RES 243:299-30.

29    Gross, M, Kost, SB, Ennis, BW, Stumpf, WE and Kumar, R (1986)
Effect of 1,25-dihydroxyvitamin D3 on mouse mammary tumor(GR) cells: Evidence for receptors, cellular uptake,inhibition of growth and alteration in morphology at physiologic concentrations of hormone.  J BONE AND MINERAL RES 1:457-467.

30    Stumpf, WE, Sar, M, Chen, K, Morin, J and DeLuca, HF (1987) 
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 TISS RES 247:453-455.

31    Stumpf, WE and O'Brien, LP (1987) 
Autoradiographic studies with 3H 1,25 dihydroxyvitamin D3 in thyroid and associated tissues of the neck region.  HISTOCHEMISTRY 87:53-58.

32    Clark, SA, Stumpf, WE, Sar, M and DeLuca, HF (1987)
1,25-dihydroxyvitamin D3 target cells in immature pancreatic islets.  AM J PHYSIOL 253:E99-E105.

33    Stumpf, WE and Downs, TW (1987)
Nuclear receptors for 1,25 (OH)2 vitamin D3 in thymus reticular cells studied by autoradiography.  HISTOCHEMISTRY 87:367-369.

34    Stumpf, WE and O'Brien, LP (1987)
1,25 (OH)2 Vitamin D3 sites of action in the brain: an autoradiographic study. HISTOCHEMISTRY 87:393-406.

35    Stumpf, WE, Sar, M and O'Brien, LP (1987)
Vitamin D sites of action in the pituitary studied by combined autoradiography-immunohistochemistry. HISTOCHEMISTRY 88:11-16.

36    Stumpf, WE, Clark, SA, O'Brien, LP and Reid, FA (1988)
1,25(OH)2 Vitamin D3 sites of action in spinal cord and sensory ganglion.  ANAT EMBRYOL 177:307-310.

37    Stumpf, WE (1988)
The endocrinology of sunlight and darkness: Complementary roles of vitamin D and pineal hormones. NATURWISSENSCHAFTEN 75:247-251.

38    Stumpf, WE (1988) 
Vitamin D-Soltriol. The heliogenic steroid hormone: Somatotrophic activator and modulator. Discoveries from histochemical studies lead to new concepts. HISTOCHEMISTRY 89:209-219.

39    Stumpf, WE, Sar, M, O'Brien, LP and Morin, J (1988)
Pyloric gastrin-producing cells and pyloric sphincter muscle cells are nuclear targets for 3H 1,25(OH)2 vitamin D3 studied by autoradiography and immunohistochemistry.  HISTOCHEMISTRY 89:447-450.

40    Stumpf, WE (1988)
The first eye; and the second, third and forth eyes: Relationships between skin, pineal, and lateral eyes. NEUROENDOCRIN. LETTERS 10:131-134.

41    Stumpf, WE, Privette, TH (1989)
Light, Vitamin D and Psychiatry. Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder  and other mental processes. PSYCHOPHARMACOL 97:285-294.

42    Schleicher G, Privette TH, Stumpf WE (1989)
Distribution of soltriol [1,25 (OH)2 vitamin D3] binding sites in male sex organs of the mouse: An autoradiographic study. J HISTOCHEM CYTOCHEM 37:1083-1086.

43    Stumpf WE, Denny ME (1989)
Vitamin D-Soltriol,light and reproduction. Am J Obst Gynecol 161:1375-1384.

44    Stumpf WE (1990)
Steroid hormones and the cardiovascular system. Direct actions of estradiol, progesterone, testosterone, gluco- and mineralcorticosteroids, and soltriol (vitamin D) on central nervous reglutory and peripheral tissues. Experientia 46:13-25.

45    Stumpf WE, Bidmon HJ, Murakami R, Heiss C, Mayerhofer A, Bartke A (1990)
Sites of action of soltriol (vitamin D) in hamster spleen, thymus, and lymph node, studied by autoradiography. Histochemistry 94:121-125.

46    Stumpf WE, Bidmon H-J (1990)
Lokalisation von 1,25-(OH)2-Vitamin D3-rezeptoren und ihre organspezifische  Verteilung in niederen Vertebraten (Pisces, Amphibia, Reptilia). Verh. Deutsch. Zool. Ges. 83:591-592.

47    Bidmon H-J, Kähnert H, Stumpf WE (1990)
Topographical distribution of target neurons for  1,25(OH)2-  vitamin D3 in the brain of lower vertebrates: Xiphophorus helleri(Pisces),Xenopus laevis(Amphibia), Anolis carolinensis (Reptilia). In: Brain-Perception-Cognition; Proc.18th Neurobiol. Conf. Göttingen, Elsner N, Roth G (eds); Thieme Verlag, Stuttgart, p 473.

48    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 39:283-289.

49    Stumpf WE, Bidmon H-J (1991)
Vitamin D-soltriol: The steroid hormone of seasonal regulation of growth and reproduction, stress and immune response, neural, endocrine autonomic, neuromuscular and cardiovascular functions. In: Vitamin D gene regulation, structure-function analysis and clinical application. Norman AW, Bouillon R, Thomasset M (eds), Walter de Gruyter, Berlin, pp 464-465.

50    Bidmon H-J, Stumpf WE (1991)
Phylogeny of nuclear receptors for 1,25-dihydroxyvitamin D3 (1,25-D3, soltriol) in lower vertebrates and insects.In: Vitamin D gene regulation, structure-function analysis and clinical application. Norman AW, Bouillion R, Thomasset M (eds), Walter de Gruyter, Berlin, 673-674.

51    Musiol IM, Stumpf WE, Bidmon H-J, Heiss C, Mayerhofer A,Bartke A (1991)
Vitamin D nuclear binding to neurons of the Alzheimer pathoclitic region of n. basalis of Meynert, central amygdaloid group and n. of the diagonal band of Broca. In: Norman AW, Bouillon R, Thomasset M (eds): Vitamin D gene regulation, structure-function analysis and clinical application. Walter de Gruyter, Berlin, pp 685-686.

52    Bidmon H-J, Gutkowska J, Murakami R, Stumpf WE (1991)
Vitamin D receptors in heart: Effects on atrial natriuretic factor. Experientia 47:958-962.

53    Bidmon H-J, Bartke A, Mayerhofer A, Heiss C, Stumpf WE (1991)
Vitamin D-soltriol receptors in the choroid plexus and ependyma: Their species specific presence. Molec Cellul Neurosciences 2:145-156.

54    Stumpf, WE and Bidmon, H-J (1991)
The steroid hormone of sunlight soltriol (vitamin D); receptors in vertebrate phylogeny and role in seasonal regulation of life. (Abstract) Proc. 15th ESCE Conf. Gen Comp Endocrinol 82:215

55    Musiol, IM, Stumpf, WE, Bidmon, H, Pilgrim, Ch (1991)
[3H]- 1,25-dihydroxyvitamin D3 (soltriol) binding in the midline and intralaminar thalamus of the sibirian hamster. Abstracts Society for Neuroscience 17:418 (172.7).

56    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. Abstracts Society for Neuroscience 17:498 (197.8).

57    Puchacz, E, Goc, A, Stumpf, WE, Bidmon, H-J, Stachowiak, EK, Stachowiak, MK (1991)
Vitamin D regulates expression of tyrosine hydoxylase gene in adrenal chromaffin cells. Abstracts Society for Neuroscience 17:981 (391.8).

58    Stumpf, WE, Bidmon, H-J, Murakami, R (1991)
Retinoic acid binding sites in adult brain, pituitary and retina. Naturwissenschaften 78:561-562.

59    Musiol IM, Stumpf WE, Bidmon H-J, Heiss C, Mayerhofer A, Bartke A (1992)
Vitamin D-Soltriol nuclear binding to neurons of the septal, substriatal, and amygdaloid area in the Siberian hamster (Photopus sungorus) brain.Neuroscience 48:841-848.

60    Stumpf WE, Bidmon H-J, Li L, Pilgrim Ch, Bartke A, Mayerhofer A, Heiss C (1992)
Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain in Siberian hamster (Phodopus  sungorus) assessed by autoradiography. Histochemistry 98:155-164.

61    Bidmon H-J, Stumpf WE (1992)
Vitamin D receptors in the forebrain of the zebra finch Taeniopygia guttata. In: Rhythmogenesis in neurons and networks (Elsner N, Richter DW, eds), Georg Thieme Verlag, Stuttgart, p 487.

62    Musiol IM, Perez-Delgado MM, Bidmon H-J, Bartke A, Stumpf WE (1992)
Comparison of the location of vitamin D receptor sites and calbindin 28kD-immunoreactivity in basal forebrain regions of the Siberian hamster. Society for Neuroscience Abstracts 18:101.

63    Stumpf WE, Bidmon H-J (1992)
Steroid  hormones and circumventricular organs. In: Circumventricular organs and brain fluid environment: Molecular and functional aspects. Ermisch A, Landgraf R, Ruehle H-J (eds), Progress in Brain Research, Vol 91,Elsevier Science Publishers BV, pp 279-283.

64    Bidmon H-J, Stumpf WE (1992)
Choroid plexus, ependyma and arachnoidea express receptors for vitamin D: Differences between "seasonal " and "non-seasonal" breeders. In: Circumventricular organs and brain fluid environment: Molecular and functional aspects. Ermisch A. Landgraf R, Rühle H-J (eds), Progress in Brain Research, Vol 91, Elsevier Science Publishers BV, pp 271-277.

65    Majumdar SS, Bartke A, Stumpf WE (1992)
Modulation by vitamin D3 of action of FSH on the Sertoli cells in immature Siberian hamsters raised in long or short photoperiod. In:Hunzicker-Dunn M, Schwartz NB (eds), Follicle Stimulating Hormone, Springer Verlag, Heidelberg, pp 310-315.

66    Perez-Delgado M, Bidmon H-J, Bartke A, Stumpf WE (1993)
Vitamin D-soltriol target cells in the Harderian gland of Siberian hamster(Phodopus sungorus. Acta anatomica 147:174-177. 

67    Schleicher G, Bartke A, Bidmon H-J, Stumpf WE (1993)
1,25(OH)2vitamin D3 binding sites in male sex organs of the Siberian  hamster (Phodopus sungorus. An autoradiographic study. J Steroid Biochem Mol Biol 46:331-335.

68    Stumpf WE, Perez-Delgado M, Li L, Bidmon H-J, Tuohimaa P (1993)
Vitamin D3 (soltriol) nuclear receptors in abdominal scent gland and skin of Siberian hamster (Phodopus sungorus) localized by autoradiography and immunohistochemistry. Histochemistry 100:115-119.

69    Majumdar SS, Bartke A, Stumpf WE (1994)
Vitamin D modulates the effects of follicle-stimulating hormone on Sertoli cell function and testicular growth in Siberian hamsters. Life Sciences 55:1479-1486.

70    Bidmon H-J, Stumpf WE (1994)
Die Verteilung von Vitamin D-Rezeptoren im Reptiliengehirn. 89. Versammlung der Anatomischen Gesellschaft, Marburg.

71    Bidmon H-J, Stumpf WE (1994)
Distribution of the nuclear receptor for vitamin D in female and male zebra finches, Taeniopygia guttata. Cell Tissue Res 276:333-345.

72    Bidmon H-J, Stumpf WE (1994)
Distribution of target cells for 1,25-dihydroxyvitamin D3 in the brain of the yellow bellied turtle Trachemys scripta. Brain Research 640:277-285.

73    Stumpf WE, Koike N, Hayakawa N, Tokuda K, Nishimiya K, Tsuchiya Y, Hirate J, Okazaki A (1994)
1,25-Dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification. Histochemistry 102:183-194.

74    Stumpf WE, Koike N, Hayakawa N, Tokuda K, Nishimiya K, Hirate J, Okazaki, Kumaki K (1995)
Distribution of 1,25-dihydroxyvitamin D3[22-oxa] in vivo receptor binding in adult and developing skin. Arch Dermatol Res 287:294-303.

75    Stumpf WE, Hayakawa N, Koike N, Hirate J, Okazaki A (1995)
Nuclear receptors for 1,25-dihydroxy-22-oxyvitamin D3 (OCT) and 1,25-dihydroxyvitamin D3 in gastric gland neck mucous cells and gastrin enteroendocrine cells. Histochemistry 103:245-250.

76    Bidmon H-J, Stumpf WE (1995)
1,25-Dihydroxyvitamin D3 binding sites in the eye and associated tissues of the green lizard Anolis carolinensis.   Histochemical Journal 27:516-523.

77    Stumpf WE (1995)
Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting. Histochem Cell Biol 104:417-427.

78    Stumpf WE (1995)
Relevance of tissue distribution studies and cytopharmacology: Utility of radioassay combined with autoradiography. (Letter to the Editor), Drug Metabolism and Disposition 23(9):885-886.

79    Bidmon H-J, Stumpf WE (1996)
Vitamin D target systems in the brain of the green lizard Anolis carolinensis. Anat Embryol 193:145-160.

80    Puchacz E, Stumpf WE, Stachowiak EK, Stachowiak MK (1996)
Vitamin D increases expression of the tyrosin hydroxylase gene in adrenal medullary cells. Molec Brain Res 36:193-196.

81    Stumpf WE (1996)
Corpora non agunt nisi in loco. (Letter to the Editor) Drug Metabolism and Disposition 24(5):507-506.

82    Bidmon H-J, Stumpf WE (1996)
Vitamin D target systems in the brain of the green lizard Anolis carolinensis. Anat Embryol 193:145-160.

83    Bidmon H-J, Radu I, Stumpf WE (1997)
Aspects of 1,25-dihydroxyvitamin D3 binding sites in fish: an autoradiographic study. Romanian Journal of Morphology and Embryology 18:91-101.

84    Stumpf WE (1998)
Receptor localization of steroid hormones and drugs: discoveries through the use of thaw-mount and dry-mount autoradiography. Braz J Medic Biol Res 31:197-206.

85    Stumpf WE (1998)
Considerations about the present and future use of autoradiography. Braz J Medic Biol Res 31:181-183.

86    Koike N, Ichikawa F, Nishii Y, Stumpf WE (1998)
Sustained osteoblast nuclear receptor binding of converted 1a,25-dihydroxyvitamin D3 after administration of 3H-1a-hydroxyvitamin D3: A combined receptor autoradiography and radioassay time course study with comparison to 3H-1a,25-dihydroxyvitamin D3. Calc Tiss Int 63:391-395.

87    Koike N, Hayakawa N, Kumaki K, Stumpf WE (1998)
In vivo dose-related receptor binding of the vitamin D analogue [3H]1,25-dihydroxy-22-oxavitamin D3 (OCT) in rat parathyroid, kidney distal and proximal tubules, duodenum, and skin, studied by quantitative receptor autoradiography. J Histochem Cytochem 46(12):1351-1358.

88    Stumpf WE (1999)
Localizing estradiol and other diffusible hormones and drugs by autoradiography and immunocytochemistry. Histochem Cell Biol 111:83-84.

89    Koike N, Endo K, Kubodera N, Kumaki K, Ikeda K, Ogata E, Stumpf WE (1999)
In vivo nuclear uptake of a vitamin D analog (OCT) in different tumor cell populations of FA-6 cancer xenograft in nude mice by receptor autoradiography. Anticancer Res 19(6B):4955-8.

90    Kawase A, Ichikawa F, Koike N, Kamachi S, Stumpf WE, Nishii Y, Kubodera N (2000)
Synthesis and pharmacokinetics of 1a-hydroxyvitamin D3 tritiated at 22 and 23 position showing high specific radioactivity. Chem Pharm Bull 48(2):215-219.

91    Stumpf WE, Bidmon H-J (2000)
“Vitamin D Mysteries”? Secretions and sloughings from skin and oral-gastrointestinal mucosa contain hormone. J Nutrition 130:264.

92     Koike N, Hayakawa N, Tokuda K, Nishimiya K, Saito K, Stumpf WE (2002)
In vivo time-course of receptor binding in the parathyroid gland of the vitamin D analogue [3H]1,25-dihydroxy-22-oxavitamin D3 compared with [3H]1,25-dihydroxyvitamin D3, determined by micro-autoradiography. Nephrol Dial Transplant 17 Suppl 10:53-7.

93    Stumpf WE (2002)
Limitations of whole body autoradiography without receptor microautoradiography. Journal of Pharmacological and Toxicological Methods 48:127-128.

94    Stumpf WE (2002)
Limitations and advantages of whole-body autoradiography in the study of tissue distribution of drugs. Response to Dr. Solon. Journal of Pharmacological and Toxicological Methods 48:127-128.

95    Stumpf WE (2003)
Drug Localization in Tissues and Cells. IDDC Press,Chapel Hill,NC.

96    Hayakawa N, Kubota N, Imai N, Stumpf WE (2004)
Receptor Microscopic Autoradiography for the study of percutaneous absorption, in vivo skin penetration, and cellular-intercellular deposition. Journal of Pharmacological and Toxicological Methods 50:131-137. 

97    Stumpf WE (2005)
Drug localization and targeting with receptor microscopic autoradiography. Journal of Pharmacological and Toxicological Methods 51(1):25-40.

98    Stumpf WE (2006)
The dose makes the medicine. Drug Discovery Today. 11:550-555.

99    Koike N, Stumpf WE (2007)
Sweat gland epithelial and myoepithelial cells are vitamin D targets. Exp Dermatology 16:94–97.

100   Stumpf WE (2007)
The main role of vitamin D: Seasonal regulation of vital functions (Editorial). High-resolution target recognition leads to a new paradigm and advanced drug development. European Journal of Drug Metabolism and Pharmacokinetics 32:1-6.

101   Stumpf WE, Hayakawa N (2007)
Salivary glands epithelial and myoepithelial cells are major vitamin D targets. Eur J Drug Metab Pharmacokinetics 32(3):123-129.

102   Stumpf WE, Hayakawa N, Bidmon HJ (2008).
Skin research and drug localization with receptor microscopic autoradiography (Review). Exp Dermatol 17(2):133-8.

103   Stumpf WE (2007)
Memo to the FDA and ICH: appeal for in vivo drug target identification and target pharmacokinetics. Drug Discovery Today 12(15/16):594-598.

104   Stumpf WE (2008)
Vitamin D and the digestive system. Eur J Drug Metab Pharmacokinetics 33(2):85-100.