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International Institute of Drug Distribution, Cytopharmacology and Cytotoxicology, Chapel Hill, NC 27516 and Institute for Neuroanatomy, University of Duesseldorf, 40225 Duesseldorf, Germany
1To whom correspondence should be addressed.
Regarding the questions raised in a recent article about the puzzle of
transfer of vitamin D activity to the D(-) animal kept in
the cage below a D(+) animal, it is stated to appear
unlikely that feces from irradiated D(+) animals could show
significant antirachitic activity and that "an alternate
possibilityactivity of grease from irradiated furdeserves
investigation" (Carpenter and Zhao 1999
). Data
published in the literature during the past 20 y offer an
additional explanation: Sloughings and secretions of the skin together
with sloughings and secretions of naso-oral (salivary) and
gastrointestinal mucosal lining are likely to contribute hormone and
metabolites as active contaminants (Stumpf 1995
).
The skin contains specific binding sites for 1,25
dihydroxycholecalciferol and analogs in keratinocytes of the epidermis,
the hair sheaths, the holokrine sebaceous glands and the sweat glands
(Perez-Delgado et al. 1999, Stumpf et al. 1979
, Stumpf et al. 1993
,
Stumpf et al. 1995
) with additional storage
capacity in intercellular secretory products and sebum. Because of the
high turnover of target cells and secretions of the skin, followed by
grooming and licking, active hormone and metabolites become available
to the surface of hairs and fur and are released continuously. We
have visualized specific vitamin D receptor binding also in the layers
of epithelium of the mouth cavity and esophagus, in certain elements of
the nasal mucosa (esp. vomeronasal organ), the Harderian gland of the
eye, and the salivary glands, from all of which active compound may be
contributed. Furthermore, radiolabeled compound is seen in glandular
ducts, and steroids are known to be excreted into the saliva.
Additionally, epithelial cells of the intestine exhibit strong nuclear
binding of 1,25-dihydroxycholecalciferol. These cells are characterized
by a high turnover and continuous sloughing.
Since these epithelial sloughings from both the entire small and large intestine are excreted with the feces, they may constitute an important source of active hormone. Clearly, skin and some of its appendices, oral-nasal mucosa and salivary gland as well as alimentary tract discharges need to be considered as sources of the maybe not so "mysterious" vitamin D transfer.
The comprehensive amounts of the bodily discharges of vitamin D, albeit considered low in the experiments reviewed by Carpenter and Zhao, may provide evidence regarding the minimum amounts of vitamin D metabolite needed by rats to prevent vitamin D deficiency-related pathologies. The latter might be of interest even for the design of new experimental strategies.
REFERENCES
1.
Carpenter K. J., Zhao L. Forgotten mysteries in the early history of vitamin D. J. Nutr. 1999;129:923-927
2. Pérez-Delgado M., Bidmon H.-J., Bartke A., Stumpf W. E. Vitamin D-soltriol target cells in the Harderian gland of Siberian hamster (Phodopus sungorus). Acta Anatomica 1993;147:174-177[Medline]
3. Stumpf W. E. Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting. Histochem. Cell Biol. 1995;104:417-427[Medline]
4. Stumpf W. E., Hayakawa N., Koike N., Tokuda K., Nishimiya K., Hirate J., Okazaki A., Kumaki K. Distribution of 1,25-dihydroxy-22-oxyvitamin D3 (OCT) in vivo receptor binding in adult and developing skin. Arch. Dermatol. Res. 1995;287:294-303[Medline]
5. Stumpf W. E., Pérez-Delgado M., Li L., Bidmon H.-J., Tuohimaa P. Vitamin D (soltriol) nuclear receptors in abdominal scent gland and skin of Siberian hamster (Phodopus sungorus) localized by autoradiography and immunohistochemistry. Histochem 1993;100:115-119
6.
Stumpf W. E., Sar M., Reid F. A., Tanaka Y., DeLuca H. F. Target cells for 1,25-dihydroxyvitamin D3 identified by thaw-mount autoradiography. Science 1979;206:1188-1190
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K. J. Carpenter and L. Zhao Vitamin D Mysteries: A Response to Stumpf and Bidmon J. Nutr., January 1, 2000; 130(2): 265 - 265. [Full Text] |
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