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.
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.


CONCLUSIONS
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.
Merck Research Laboratories, West Point, PA 19486, USA.
Zoltan
Z
Erdos
Kara
K
Pearson
Michael
M
Goedken
Karsten
K
Menzel
Frank D
FD
Sistare
Warren E
WE
Glaab
Louise Parks
LP
Saldutti
D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000633:toxicity; D002219:Carbamates / Q000008:administration & dosage / Q000633:toxicity; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000633:toxicity; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity; D005001:Ethionine / Q000008:administration & dosage / Q000633:toxicity; D006582:Hexachlorophene / Q000008:administration & dosage / Q000633:toxicity; D006588:Hexanones / Q000008:administration & dosage / Q000633:toxicity; D007265:Inhibins / Q000097:blood*; D008297:Male; D008698:Mesylates / Q000008:administration & dosage / Q000633:toxicity; D009583:Nitrofurazone / Q000008:administration & dosage / Q000633:toxicity; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects / Q000473:pathology
D001562:Benzimidazoles; D002219:Carbamates; D004785:Environmental Pollutants; D006588:Hexanones; D008698:Mesylates; C422364:inhibin B; D003993:Dibutyl Phthalate; D004997:Ethinyl Estradiol; D007265:Inhibins; C011269:2,5-hexanedione; C002994:ethylene dimethanesulfonate; C006698:carbendazim; D006582:Hexachlorophene; D005001:Ethionine; D009583:Nitrofurazone