Early postnatal treatment with transforming growth factor α does not alter nonreproductive behavior

Estrogen acting during the critical developmental period has been postulated to defeminize and possibly masculinize male sexual behavior. Transforming growth factor α (TGFα) also may be involved, because this growth factor, at least partly, mediates the mitotic effects of estrogen on target tissues. Male transgenic mice overexpressing TGFα have elevated serum estradiol (E2) levels and they exhibit feminization of many nonreproductive actions, suggesting that either TGFα and/or E2, or both, participate in the control of some nonreproductive behavior. Male and female 6D-1 mice were treated with 4 μg of recombinant human TGFα or 2-4 μg E2 during the first 3 days of life. Although early TGFα treatment accelerates physical development and influences the growth of the uterus and mammary gland, it failed to have any effect on behavior, either in male or female mice. Early E2 treatment significantly lengthened immobility time in the swim test and reduced voluntary alcohol intake among the male mice. No changes in locomotor activity or aggressive behavior were noted. The expression of TGFα mRNA in the brainstem of adult male mice was not altered following neonatal TGFα or E2 treatment. However, neonatal exposure to TGFα caused a moderate elevation in TGFα mRNA expression in the female brainstem. Our results indicate that in male, but not in female mice, an excess of E2 during early life affects some nonreproductive behavior. Furthermore, early treatment with recombinant human TGFα does not alter nonreproductive behavior in mice.