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Expression of parathyroid hormone-related protein in the partially obstructed and reversed rabbit bladder

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Abstract

Objectives

Parathyroid hormone-related protein (PTHrP), the main factor responsible for malignant hypercalcemia, is produced by a wide range of normal and malignant tissues. Prior studies in the rabbit model demonstrated that partial bladder outlet obstruction results in calcium-dysregulation characterized by a marked increase in free calcium within the smooth muscle compartment and the stimulation of calcium-activated enzymes, such as calpain and phospholipase A2.

Methods

Twenty-four male New Zealand white rabbits were divided into four groups of six each. Following 4 weeks of obstruction, one group of animals was killed, while outlet obstruction was reversed in two additional groups of animals, which were killed 4 and 8 weeks after relieving the obstruction. A group with six sham-operated rabbits served as controls. The expression and localization of PTHrP were detected in muscle and mucosa by immunohistochemistry, using a PTHrP-specific antibody.

Results

In the sham-operated group, rabbit bladders showed a low expression of PTHrP in both the mucosa and muscle layers. PTHrP in the 4-week obstructed bladder group, in muscle and mucosa, were 266% and 134% higher than the sham group, respectively. Strong PTHrP immunostaining persisted in the 4-week reversal groups, but it returned to the sham level after 8 weeks of reversal in the muscle layer. As mentioned about the mucosa layer, the PTHrP level returned to control levels more rapidly after 4 weeks of reversal and continued after 8 weeks of reversal.

Conclusion

This study showed that PTHrP is increased after partial bladder outlet obstruction and decreased after relieving the obstruction.

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Acknowledgements

This material is based upon work supported in part by the Office of Research and Development Medical Research Service, Department of Veteran’s Affairs; in part by NIH grant RO-1-DK 067114; and in part by Fundacion Conchita Rabago. We wish to thank Pedro Esbrit for critical review of the manuscript.

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Authors and Affiliations

  1. Departamento de Histología, Facultad de Medicina, Universidad de Castilla-La Mancha, C/ Almansa s/n, 02006, Albacete, Spain

    Francisco C. Perez-Martinez

  2. Stratton Veterans Affairs Medical Center, Albany, NY, USA

    Francisco C. Perez-Martinez, Yung-Shun Juan, Wei-Yu Lin, Anita Mannikarottu & Robert M. Levin

  3. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

    Yung-Shun Juan

  4. Department of Urology, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Wei-Yu Lin

  5. Department of Pediatric Surgery, Gulhane Military Medical Faculty, Ankara, Turkey

    Ahmet Guven

  6. Albany Medical College, Albany, NY, USA

    Anita Mannikarottu & Robert M. Levin

  7. Albany College of Pharmacy, Albany, NY, USA

    Robert M. Levin

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  1. Francisco C. Perez-Martinez
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  2. Yung-Shun Juan
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Correspondence to Francisco C. Perez-Martinez.

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Perez-Martinez, F.C., Juan, YS., Lin, WY. et al. Expression of parathyroid hormone-related protein in the partially obstructed and reversed rabbit bladder. Int Urol Nephrol 41, 505–511 (2009). https://doi.org/10.1007/s11255-008-9485-x

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  • DOI: https://doi.org/10.1007/s11255-008-9485-x

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