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Endocrine Abstracts (2005) 9 P136

BES2005 Poster Presentations Steroids (17 abstracts)

Establishment of physiological and supra-physiological testosterone dosing regimen in mice

JE Nettleship 1 , RD Jones 1 , KS Channer 2,3 & TH Jones 1,4


1Hormone and Vascular Biology Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, UK; 2Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Trust, Sheffield, UK; 3Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UK; 4Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Barnsley District General Hospital NHS Trust, Barnsley, UK.

Objective: The aim of this study was to determine dosing regimen to replace testosterone to physiological levels in the testicular feminised (Tfm) mouse, and also to produce similar supraphysiological testosterone concentrations in Tfm and XY littermates.

Methods: Eight-week-old Tfm (n=66) and XY littermate controls (n=24) received a single 10 microlitre intramuscular injection of testosterone (Sustanon 100 - 100 milligrams testosterone per litre, or Sustanon 250 - 250 milligrams testosterone per litre). Mice were sacrificed at serial intervals: 1,2,4,7,10 or 14 days post injection. Whole blood was centrifuged at 3000rpm for 10 minutes and the serum collected. Measurements of total testosterone were made via ELISA. To ensure reproducibility of this pharmacokinetic profile additional Tfm (n=38) and XY (n=22) mice received a second injection at day 14 and were sacrificed at day 15, 16, 21 or 28.

Results: As mean (SEM). Basal levels of testosterone in Tfm and XY mice were 1.03 (0.05) and 14.2 (3.79) nM respectively (p<0.0001). In Tfm mice receiving Sustanon 100, serum levels of testosterone after 1,2,4,7,10 and 14 days were; 56.3 (6.04), 41.0 (6.42), 31.8 (4.86), 14.0 (4.24), 7.11 (1.61), 3.63 (1.25) nM respectively: AUC=17.5nM. In Tfm mice receiving Sustanon 250, serum levels of testosterone after 1,2,4,7,10 and 14 days were; 477.1 (44.3), 397.8 (40.0), 298.5 (10.6), 267.9 (29.3), 275.0 (25.9), 211.5 (42.8) nM respectively: AUC=287.9nM. In XY mice receiving Sustanon 250, serum levels of testosterone after 1,2,4,7,10 and 14 days were; 456.3 (22.3), 322.5 (44.5), 190.6 (21.9), 199.3 (89.6), 265.3 (22.3), 226.5 (46.4) nM respectively: AUC=287.5nM (p>0.05). Second cycle analysis revealed statistically similar serum levels of testosterone.

Conclusion: Reproducible physiological testosterone replacement is achieved by a fortnightly 10 microlitre intramuscular injection of Sustanon 100 in Tfm mice. Reproducible supra-physiological testosterone concentrations were produced by fortnightly 10 microlitre intramuscular injections of Sustanon 250 in Tfm and XY littermates.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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