Fig. 6.

Time course for continuous GH feminization of P450 gene expression in adult male liver. Model shown is based on data presented in Holloway et al. (2006); hypothetical regulatory interactions are indicated by question marks. Female-specific repressors (Laz et al., 2007), are rapidly induced in male liver by continuous GH treatment and are proposed to down-regulate male-specific genes. The latter genes are proposed to include one or more male-specific repressors, whose down-regulation leads to de-repression of female-specific genes, such as Cyp2b9 and Cyp2b10; these Cyp2b genes require several days of continuous GH treatment for induction (Holloway et al., 2006). A distinctly longer time frame (≥7 days) is required for derepression leading to induction of the female-specific Cyp3a genes, which may involve epigenetic mechanisms, as discussed in the text and diagrammed in Fig. 5.