Regulation der Calcium-Homöostase beim kleinen Wiederkäuer: Einfluss von Ca-Versorgung, Laktation und Calcitriol
Zusammenfassung der Projektergebnisse
For ruminants, marked differences to monogastric species have been described concerning the localization and vitamin D sensitivity of gastrointestinal calcium absorption, particularly with respect to the forestomach compartment. Therefore in the first part of our investigations, we investigated gastrointestinal calcium transport of sheep as influenced by a dietary calcium restriction and/or a supraphysiological dosage of exogenous calcitriol. Using the Ussing-chamber technique, we determined calcium and mannitol flux rates to differentiate between para- and transcellular calcium transport in rumen, duodenum, jejunum and colon. Expression of epithelial calcium channels, calbindin-D9K, and basolateral extrusion mechanisms was determined by quantitative RT-PCR and Western blot analysis. Active calcium transport could be demonstrated in jejunum and rumen. A significant stimulation of jejunal calcium absorption was only observed in animals treated with calcitriol. The alimentary calcium restriction alone did not result in significant effects indicating a less effective intestinal adaptation to alimentary calcium restriction than observed in monogastric animals. The observed ruminal calcium transport was not affected at all, neither by the diet nor the calcitriol treatment. Furthermore, no significant expression of epithelial calcium channels or calbindin-D9K could be detected in the rumen; therefore it is concluded that calcium transport in the forestomachs is probably mediated by a different, so far unknown mechanism. Many studies aimed at understanding calcium homeostasis in the cow use sheep or goats as ruminant models. However, the comparability of relevant homeostatic processes between ruminant species has not been assessed. Therefore in the second part of this project, we investigated whether the mechanisms of maintaining calcium homeostasis are similar in sheep and goats. Dietary calcium of goats was restricted along with treatment with calcitriol in a similar protocol to that presented above with sheep. Plasma calcium and phosphate and parameters of bone metabolism were analyzed. Gastrointestinal calcium transport was characterized in vitro in Ussing chambers. The expression of apical epithelial calcium channels, calbindin-D9K, and the basolateral plasma membrane Ca2+-ATPase was determined by quantitative RT-PCR and Western blot analysis. In contrast to sheep, the goats were able to compensate for low dietary calcium supply by increasing active calcium absorption in the small intestine, especially in the jejunum. As in sheep, the observed ruminal calcium transport of goats was affected neither by the calcium restricted diet nor by the calcitriol treatment, thus indicating again the presence of an alternative, vitamin D-independent mechanism of calcium transport in the forestomachs. These results demonstrate that mechanisms for maintaining calcium homeostasis differ significantly between ruminant species. Finally, in the third part of this project adaptation of calcium homeostasis in the specific situation of high calcium demand, namely during lactation, was elucidated in sheep and goats. In summary, sheep appear to regulate calcium homeostasis via bone mobilization rather than at the gastrointestinal level (exception mucosal VDR). In contrast, in lactating goats both pathways, bone as well gastrointestinal tract, are involved in controlling calcium metabolism.
Projektbezogene Publikationen (Auswahl)
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(2009): Expression of Ca channel TRPV6 in ovine epithelial tissue. Vet. J. 182:294-300
Wilkens, M.R., Kunert-Keil, C., Brinkmeier, H., Schröder, B.
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(2010): Effects of 1,25-dihydroxyvitamin D3 on calcium and phosphorus homeostasis in sheep fed either adequate or restricted in calcium content. Domest. Anim. Endocrinol. 38:190-199
Wilkens, M.R., Mrochen, N., Breves, G., Schröder, B.
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Untersuchungen zur Regulation der jejunalen Ca-Resorption beim Schaf. 2010
Nina Mrochen
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(2011): Gastrointestinal calcium absorption in sheep is mostly insensitive to an alimentary induced challenge of calcium homeostasis. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 158:199-207
Wilkens, M.R., Mrochen, N., Breves, G., Schröder, B.
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(2012): In contrast to sheep, goats adapt to dietary calcium restriction by increasing intestinal absorption of calcium. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 163:396-406
Wilkens, M.R., Richter, J., Fraser, D.R., Liesegang, A., Breves, G., Schröder, B.
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Untersuchungen zum Einfluss der Laktation auf die gastrointestinale Calcium- und Phosphat-Absorption bei Schaf und Ziege. 2013
Julia Richter
