Effect of Sex, Intrauterine Position and Androgen Manipulation on the Development of Brain Aromatase Activity in Fetal Ferrets

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Abstract
Experiments were conducted to explore the possible relationship between testicular androgen secretion and the development of brain aromatase activity in fetal ferrets. Aromatase activity in the preoptic+mediobasal hypothalamus and temporal lobe was similar in fetuses of both sexes between embryonic Days 26 and 36 even though whole body androgen content was invariably higher in males than females. Whole body androgen content was significantly higher in females located caudally (downstream) from two or more as opposed to zero or one males in the same uterine horn; nevertheless their brain aromatase activity was similar. Finally, maternal treatment with either the androgen receptor antagonist Flutamide or 5alpha-dihydrotestosterone propionate beginning on gestational Day 24 did not affect brain aromatase activity in fetal offspring of either sex, delivered on embryonic Day 34. Previous studies suggest that the biosynthesis of estrogen in the fetal ferret brain is normally greater in males than females. The present results suggest that this sex difference results primarily from increased androgenic substrate being available to non-saturated aromatizing enzymes and not from an androgen-dependent activation of aromatase.