The Inhibin B Response to a Motilin Receptor Agonist in Male Rats
Article first published online: 24 JAN 2013
© 2013 Wiley Periodicals, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Special Issue: Part B: Developmental and Reproductive Toxicology
Volume 98, Issue 1, pages 63–71, February 2013
How to Cite
Ziejewski, M. K., Vidal, J. D., Stanislaus, D., Apostoli, A., Chowdhury, P. and Laffan, S. (2013), The Inhibin B Response to a Motilin Receptor Agonist in Male Rats. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 98: 63–71. doi: 10.1002/bdrb.21042
- Issue published online: 5 FEB 2013
- Article first published online: 24 JAN 2013
- Manuscript Accepted: 12 DEC 2012
- Manuscript Received: 10 DEC 2012
- Toxicology and the Fertility and Endocrinology
- Inhibin B;
- testis histopathology;
- circulating biomarker
In a repeat oral dose toxicity study, all of 16 male rats given 100 mg/kg/day GSK1322888 sustained testicular injury after 4 weeks of treatment; the findings were not reversible after 12 weeks off-dose. The current study was conducted to further characterize testicular toxicity and to explore the possible relationship between onset of lesions, and changes in circulating hormone levels.
Male Sprague Dawley rats were orally administered 30 or 100 mg/kg/day GSK1322888 for 2 weeks with a 4-week off-dose period. Blood was collected via tail vein twice during the treatment period (days 4 and 11) and three times during the off-dose period (days 28, 36, and 42) for measurement of serum testosterone, dihydrotestosterone, and Inhibin B, luteinizing hormone, and follicle stimulating hormone concentrations. A histopathologic examination of testes was performed at the end of the treatment and off-dose periods.
At 100 mg/kg/day, microscopic findings of the testis (degeneration of the germinal epithelium) were evident for 9 of 10 male rats on day 14 and all 10 rats at the end of the 4-week recovery period. There was no testicular toxicity observed at 30 mg/kg/day. During all stages of evaluation, there was no apparent difference among control and treated animals in hormone concentrations.
There was poor correlation between changes in serum levels of Inhibin B and testis histopathology. Based on these observations, the utility of Inhibin B as a hormonal marker for germ cell toxicity is limited.