The inhibin B response in male rats treated with a GnRH agonist and an endothelin receptor antagonist.
BACKGROUND
This study examined the correlation between Inhibin B and testicular pathology.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Global Safety Assessment, Astra Zeneca Research&Development, Alderley Park, Macclesfield, United Kingdom. michelle.coulson@astrazeneca.com
Michelle
M
Coulson
Terri
T
Mitchard
Sue
S
Bickerton
Jayne
J
Harris
Catherine
C
Betts
Jane
J
Stewart
D000818:Animals; D065128:Endothelin Receptor Antagonists; D004785:Environmental Pollutants / Q000633:toxicity*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D007265:Inhibins / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D065128:Endothelin Receptor Antagonists; D004785:Environmental Pollutants; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone