Inhibin B Response to Testicular Toxicants Hexachlorophene, Ethane Dimethane Sulfonate, Di-(n-butyl)-phthalate, Nitrofurazone, DL-Ethionine, 17-alpha Ethinylestradiol, 2,5-Hexanedione, or Carbendazim Following Short-Term Dosing in Male Rats

Authors


Correspondence to: Louise Parks Saldutti, Merck Research Laboratories, WP45-119, West Point, PA 19486. E-mail: louise_saldutti@merck.com

Abstract

BACKGROUND

Inhibin B is a heterodimer glycoprotein that downregulates follicle-stimulating hormone and is produced predominantly by Sertoli cells. The potential correlation between changes in plasma Inhibin B and Sertoli cell toxicity was evaluated in male rats administered testicular toxicants in eight studies. Inhibin B fluctuations over 24 hr were also measured.

METHODS

Adult rats were administered one of eight testicular toxicants for 1 to 29 days. The toxicants were DL-ethionine, dibutyl phthalate, nitrofurazone, 2,5-hexanedione, 17-alpha ethinylestradiol, ethane dimethane sulfonate, hexachlorophene, and carbendazim. In a separate study plasma was collected throughout a 24-hr period via an automatic blood sampler.

RESULTS

Histomorphologic testicular findings included seminiferous tubule degeneration, round and elongate spermatid degeneration/necrosis, seminiferous tubule vacuolation, aspermatogenesis, and interstitial cell degeneration. There was a varying response of plasma Inhibin B levels to seminiferous tubule toxicity, with three studies showing high correlation, three studies with a response only at a certain time or dose, and two studies with no Inhibin B changes. In a receiver operating characteristics exclusion model analysis, where treated samples without histopathology were excluded, Inhibin B showed a sensitivity of 70% at 90% specificity in studies targeting seminiferous tubule toxicity.

CONCLUSION

Decreases in Inhibin B correlated with Sertoli cell toxicity in the majority of studies evaluated, demonstrating the value of Inhibin B as a potential biomarker of testicular toxicity. There was no correlation between decreases in Inhibin B and interstitial cell degeneration. In addition, a pattern of Inhibin B secretion could not be identified over 24 hr.

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