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The Inhibin B Response in Male Rats Treated with a GnRH Agonist and an Endothelin Receptor Antagonist


Correspondence to: Dr. Michelle Coulson, Global Safety Assessment, Astra Zeneca R&D, Alderley Park, Macclesfield, SK10 4TG, UK. E-mail:



This study examined the correlation between Inhibin B and testicular pathology.


Male Han Wistar rats (approximately 10 weeks old) were administered either vehicle or an endothelin receptor antagonist (ET-An) orally for 28 days or a Gonadotropin Releasing Hormone (GnRH) agonist (GnRH-A) as a subcutaneous implant on day 1. Ten animals/group/time point were killed on days 4, 8, 15, and 29 (controls on days 15 and 29) for testes weights and histopathology. In-life blood samples were taken on days 4, 8, 15, and 29 to measure Inhibin B, Follicle-Stimulating Hormone (FSH), and Lutenising Hormone (LH), and at necropsy for the same hormones plus testosterone.


Plasma Inhibin B showed a wide concentration range in controls (group means 76.4–184.2 pg/ml; individual animals 17.8–381 pg/ml). GnRH-A caused decreased testes weights plus degenerative testicular pathology from day 4 with partial recovery by day 29. Statistically significant reductions in Inhibin B were observed at all time points and appeared to track the development and partial recovery of the pathology (generally <50 pg/ml on days 4–15; group mean 92 pg/ml on day 29). ET-An produced an increase in testes weights and a nondegenerative lesion of minimal tubular dilatation. There was a trend for lower Inhibin B values (30–50%) at all time points, including on day 4 when tubular dilatation was not yet evident.


Inhibin B showed a good correlation with testicular pathology for GnRH-A, and following ET-An administration appeared to give a signal that might reflect changes in tubular function in the absence of degenerative pathology.