Endocrine Abstracts

Background: The testicular feminised (Tfm) mouse exhibits an X-linked single base-pair deletion in the gene encoding the androgen receptor. Gene transcription produces a truncated form of the receptor protein, which has a conformational change in the androgen binding site, preventing androgen binding. Affected male animals (XTfmY) are rendered androgen insensitive and 17-alpha hydroxylase deficient, a key enzyme in the steroidogenesis pathway. XTfmY males have reduced circulating levels of testosterone because of this deficiency, but the effect on the circulating levels of other steroids is unknown.

Methods: Tfm mice were regenerated from frozen embryos obtained from the MRC mouse genome project, Harwell, Oxfordshire. Adult (9-12 week old) XTfmY and XY male littermates were killed via an approved schedule 1 method, the chest cavity opened, and blood collected following severance of the thoracic aortae. Blood was spun in a centrifuge for 10 minutes at 3000rpm, the plasma collected, and total cholesterol, testosterone, progesterone and cortisol levels measured via commercially available ELISA kits.

Results. Hormone levels are expressed as mean (sem) and analysed via students unpaired t test. XTfmY males (n=39) had significantly higher circulating levels of cholesterol; 3.6 (0.1) mM compared to XY males (n=35); 3.2 (0.5) mM (P<0.05). XTfmY males (n=46) had significantly lower circulating levels of testosterone; 1.8 (0.3) nM compared to XY males (n=40); 9.3 (1.5) nM (P<0.001). There was no significant difference in the circulating level of progesterone in XTfmY males (n=7); 4.0 (0.4) nM, and XY littermates (n=26); 4.9 (0.6) nM (P=0.48), or in the circulating level of cortisol in XTfmY males (n=21); 28.1 (0.5) nM, and XY littermates (n=23); 30.8 (2.2) nM (P=0.25).

Conclusion: Tfm mice have reduced circulating levels of testosterone and elevated circulating levels of cholesterol, the product and substrate of the portion of the steroidogenesis pathway mediated via the enzyme 17-alpha hydroxylase.