The Inhibin B Response to a Motilin Receptor Agonist in Male Rats

Ziejewski, Mary K.; Vidal, Justin D.; Stanislaus, Dinesh; Apostoli, April; Chowdhury, Probash; Laffan, Susan

doi:10.1002/bdrb.21042

Cited by 2 publications

(4 citation statements)

References 23 publications

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“…The large scale of this multi-corporation consortium study was able to confirm inhibin B decreases after sufficient damage, regardless of mechanism or toxicant class (Chapin et al, 2013b;Coulson et al, 2013b;Enright et al, 2013;Erdos et al, 2013;Sonee et al, 2013). However, analytic and interanimal variability will make it difficult to sensitively and reliably detect treatment-related decreases (Breslin et al, 2013;Chapin et al, 2013b;Ziejewski et al, 2013). Decreases in inhibin B were detected when significant testicular lesions were observed; however, decreases were generally not detected with less severe pathology or prior to the development of notable pathology.…”

Section: Figmentioning

confidence: 90%

“…Beyond technical performance, the consortium was most interested in the correlation between decreases in circulating inhibin B levels and the development of testicular pathology in the rat; therefore, a series of rat pathogenesis studies were conducted with approximately 20 different compounds (Table 2) covering diverse mechanisms of testicular toxicity across different laboratories (AbbVie, AstraZeneca, Boehringer Ingelheim, Covance, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Pfizer, and Sanofi) and reported in a special issue of Birth Defects Research Part B (98[1], 2013) (Breslin et al, 2013;Chapin and Kim, 2013;Chapin et al, 2013aChapin et al, , 2013bCoulson et al, 2013b;Enright et al, 2013;Erdos et al, 2013;Moffit et al, 2013;Pfaff et al, 2013;Sonee et al, 2013;Stewart et al, 2013;Ziejewski et al, 2013). Exposure scenarios and recovery periods varied between companies to reflect real-world testing strategies.…”

Section: Figmentioning

confidence: 99%

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SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures

Dere

Anderson

Coulson

et al. 2013

Toxicological Sciences

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Testicular toxicity is an important safety endpoint in drug development and risk assessment, but reliable and translatable biomarkers for predicting injury have eluded researchers. However, this area shows great potential for improvement, with several avenues currently being pursued. This was the topic of a symposium session during the 2013 Society of Toxicology Annual Meeting in San Antonio, TX, entitled "Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures." This symposium brought together stakeholders from academia, government, and industry to present the limitations and drawbacks of currently used indicators of injury and discussed the ongoing efforts in developing more predictive biomarkers of injury. The presentations highlighted the early challenges of using circulating inhibin B and microRNA levels, and sperm messenger RNA transcript abundance and DNA methylation profiles, as novel biomarkers of testicular toxicity.

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Section: Figmentioning

confidence: 90%

Section: Figmentioning

confidence: 99%

SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures

Dere

Anderson

Coulson

et al. 2013

Toxicological Sciences

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“…And the dogma holds that Inhibin B acts as the feedback partner for Follicle Stimulating Hormone (FSH) (reviewed in Makanji et al, 2011). But this relationship is clearly neither 1:1 nor linear (see Ziejewski et al, 2013, Table 2 and Chapin et al, 2013, Fig. 4) and in some cases, no relationship between Inhibin B and FSH could be found (for humans, Carlsen et al, 1999).…”

Section: Biologymentioning

confidence: 99%

“…We did not determine the specificity of the protein (i.e., that it comes only from the testis). The pathogenesis correlation studies are reported in the nine preceding articles in this issue of Birth Defects Research (Breslin et al, ; Chapin et al, ; Coulson et al, ; Enright et al, ; Erdos et al, ; Moffit et al, ; Pfaff et al, ; Sonee et al, ; Ziejewski et al, ). The present paper is intended to review and discuss the data presented by each of these preceding reports.…”

Section: Introductionmentioning

confidence: 99%

Summary of the HESI Consortium Studies Exploring Circulating Inhibin B as a Potential Biomarker of Testis Damage in the Rat

Chapin

Weinbauer

Thibodeau

et al. 2013

Birth Defects Research Pt B

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The Developmental and Reproductive Toxicity Technical Committee of the Health and Environmental Sciences Institute hosted a working consortium of companies to evaluate a new commercially available analytic assay for Inhibin B in rat serum or plasma. After demonstrating that the kit was stable and robust, the group performed a series of independent pathogenesis studies (23 different compound/investigator combinations) designed to examine the correlation between the appearance of lesions in the testis and changes in circulating levels of Inhibin B. These studies were reported individually in the previous articles in this series (this issue), and are discussed in this paper. For roughly half of these exposures, lesions appeared well before Inhibin B changed. A few of the studies showed a good correlation between seminiferous tubule damage and reduced circulating Inhibin B levels, while for seven exposures, circulating Inhibin B was reduced with no detectable alteration in testis histology. Whether this indicates a prodromal response or a false-positive signal will require further investigation. These exceptions could plausibly suggest some value of circulating Inhibin B as a useful biomarker in some circumstances. However, for roughly half of these exposures, Inhibin B appeared to be a lagging biomarker, requiring significant damage to the seminiferous tubules before a consistent and credible reduction in circulating levels of Inhibin B was observed.

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The Inhibin B Response to a Motilin Receptor Agonist in Male Rats

Abstract: 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.

Cited by 2 publications

References 23 publications

SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures

SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures

Summary of the HESI Consortium Studies Exploring Circulating Inhibin B as a Potential Biomarker of Testis Damage in the Rat

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