Endocrine Abstracts (2004) 7 P208

The testicular feminised mouse: physiological testosterone replacement

JE Nettleship1, CM Biggins2, RD Jones1, KM English3, KS Channer3 & TH Jones4


1Hormone and Vascular Biology Group, Academic Unit of Endocrinology, Division of Genomic Medicine, The University of Sheffield, Sheffield, UK; 2Department of Clinical Chemistry, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK; 3Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK; 4Centre for Diabetes & Endocrinology, Barnsley District General Hospital, Barnsley District General Hospital NHS Trust, Barnsley, UK.


Testicular feminised (Tfm) mice bear an X-linked, single base pair deletion in the gene encoding the classical androgen receptor(1) consequently these animals express a truncated, non-functional form of the receptor protein. Affected animals (XTfmY) are rendered insensitive to actions mediated via this receptor. The Tfm mouse is therefore an excellent model for studying non-genomic testosterone signalling mechanisms. Unfortunately, Tfm mice are also deficient in the enzyme 17 alpha-hydroxylase, a key constituent of the steroidogenesis pathway, and therefore exhibit a circulating testosterone profile that is aproximately ten-fold lower than XY littermates (1.5 nanomoles per litre compared to 15 nanomoles per litre)(2). The aim of this study was to determine a dosing regimen to physiologically replace testosterone in the Tfm mouse.

Eight week old XTfmY mice (n=35) received a single 10 microlitre intramuscular injection of 100 milligrams per litre of testosterone (Sustanon100). Blood was taken at serial intervals (1,2,4,7,10 or 14 days post injection) via an approved schedule-1 method. Whole blood was centrifuged at 3000rpm for 10 minutes and the serum collected. Quantitative measurements of total testosterone and 17 beta-oestradiol were then made via ELISA.

Serum levels of total testosterone significantly increased from 1.00 plus/minus 0.08 nanomoles per litre to 56.3 plus/minus 6.04 nanomoles per litre (p<0.0001) after 1 day, returning to basal levels at 14 days. The area under the curve for this period was 20.6 nano molar. Serum levels of 17 beta-oestradiol also increased significantly from 380.4 plus/minus 44.3 nanomoles per litre to 732.5 plus/minus 106.4 nanomoles per litre (p<0.05) at 2 days, returning to basal levels at 4 days.

A single intramuscular injection of 10 microlitres Sustanon100 is sufficient to physiologically replace testosterone in the Tfm mouse over a 14 day period.

1. Charest NJ et al. Mol.Endocrinol. 1991,5,573-581

2. Jones RD et al. Eur.J.Endocrinol. 2003,148,111-120

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