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Biology of Reproduction 63, 651-657 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Regular Article, PCC

Generation of Cyclic Guanosine Monophosphate by Heme Oxygenases in the Human Testis—A Regulatory Role for Carbon Monoxide in Sertoli Cells?1

Ralf Middendorff2,a, Monika Kumma, Michail S. Davidoffa, Adolf F. Holsteina, and Dieter Müllerb

a Institute of Anatomy, University of Hamburg, 20246 Hamburg, Germany b Institute for Hormone and Fertility Research, University of Hamburg, 22529 Hamburg, Germany

ABSTRACT

Previous studies have demonstrated that cGMP is produced by nitric oxide-mediated activation of soluble guanylyl cyclase (sGC) in seminiferous tubules of the human testis. It is not known, however, whether carbon monoxide (CO), another activator of sGC, is also involved in testicular function. To address this issue, testicular probes from 65- to 75-yr-old men have been examined. The CO-generating enzyme, heme oxygenase-1 (HO-1), could be localized by immunohistochemical and immunoblot analyses to Sertoli cells. In these cells, HO-1 is detectable in adluminal cell compartments, whereas sGC immunoreactivity is distributed exclusively in basal compartments. Treatments of isolated tubules with either sodium arsenite, known to induce HO-1, or hematin, an HO substrate, resulted in 4.4- and 1.8-fold, respectively, increases in cGMP levels. ODQ, a specific sGC inhibitor, inhibited completely the sodium arsenite-stimulated cGMP production. Moreover, the HO inhibitor zinc protoporphyrin-IX and the CO scavenger hemoglobin both significantly reduced (77% or 46% of control, respectively) tubular cGMP generation. These findings, demonstrating for the first time a link between HO-1 activity in Sertoli cells and sGC-dependent cGMP production in seminiferous tubules, suggest a functional role of CO in the human testis.

FOOTNOTES

First decision: 16 August 1999.

1 The present study was supported by grants from the Deutsche Forschungsgemeinschaft (Mi 637/1-1).

2 Correspondence: Ralf Middendorff, Institute of Anatomy, University of Hamburg, Martinistr. 52, 20246 Hamburg, Germany. FAX: 49 40 42803 4966; middendo{at}uke.uni-hamburg.de




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