The feminine profile of continuous
growth hormone secretion was restored at various concentrations to hypophysectomized,
thyroxine-supplemented female rats to determine the minimum signaling concentrations of the
hormone required to maintain female-like expression levels of gender-dependent hepatic
cytochrome P450s (P450s). Rat
growth hormone was infused by intraperitoneally implanted osmotic minipumps, and the resulting circulating concentrations and profiles were determined by radioimmunoassay of serially collected plasma samples. Restoration of feminine
growth hormone profiles at 3% of physiological concentration completely suppressed male-specific CYP2C11, CYP2C13, CYP2A2, and CYP3A2. Although significant levels of female-dependent
isoforms were expressed at this
growth hormone concentration, their full expression required, somewhat higher plasma concentrations of the
hormone; CYP2A1 and
5 alpha-reductase were increased to normal female levels with only 6-12% of physiological concentrations of the
hormone, normal expression levels of CYP2C12 required approximately 12-25% physiological
hormone levels, and CYP2C7 required approximately 25-50% of the normal
growth hormone profile to attain female-like expression levels. When determined,
protein and specific catalytic activities were in agreement with
mRNA levels, supporting the conclusion that
growth hormone regulates gender-dependent expression of P450
isoforms by transcription initiation. There was little effect of gender,
hypophysectomy, or
growth hormone replacement on CYP2C6,
growth hormone receptor, and
growth hormone-binding protein mRNAs. In contrast,
insulin-like growth factor-1
mRNA was sexually dimorphic (male > female), virtually disappeared after
hypophysectomy, and was restored to female-like levels with plasma
growth hormone concentrations equaling 12-25% of normal. These findings demonstrate the effectiveness of nominal
growth hormone concentrations (undetectable by available radioimmunoassay) in an otherwise feminine plasma profile to maintain female-like expression levels of gender-dependent P450s.