The Inhibin B Response in Male Rats Treated With Two Drug Candidates

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Chapin RE, Alvey JD, Goldstein RA, Dokmanovich MG, Reagan WJ, Johnson K, Geoly FJ
  • Journal Name : Birth Defects Research Part B: Developmental and Reproductive Toxicology

Birth Defects Research Part B: Developmental and Reproductive Toxicology. 2013;98(1):54-62

Background: Serum Inhibin B was measured in two studies of known testis-toxic drug candidates.

Methods and Results: Study 1 was for a compound for Hepatitis C, and utilized a 10-week dosing period, followed by mating and necropsy of half of each group, and then a 12-week recovery period for the remaining animals. At the postmating necropsy, 6 of 15 high-dose males had testis lesions; Inhibin B was significantly reduced in all animals in that group. The mid-dose group had no lesions but significantly reduced serum Inhibin B. At recovery, 9 of 15 high-dose males showed damage in testes; serum Inhibin B levels were not different from controls. Inhibin B appeared to both overreport and underreport testis damage in Study 1. Study 2 was an acute pathogenesis study for an antibacterial compound, using control and two dose levels and multiple time points (days 5, 8, 15, 22, and then untreated until day 71). At each time point blood was sampled from all remaining rats and five/group were killed for histologic evaluation. The low-dose group had minimal to moderate lesions, while serum Inhibin B was never changed. The high-dose animals progressed quickly from minimal lesions to being broadly and moderately affected; serum Inhibin B levels were reduced at days 8 and 15 only. In Study 2, Inhibin B appeared less sensitive than histology, except at the extremes of testis damage, when Inhibin B was routinely low.

Conclusion: We conclude that in these two studies there was a poor correlation between changes in serum levels of Inhibin B and testis histopathology.

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