Intrinsic signals in the sexually dimorphic circulating growth hormone profiles of the rat.

Male rats secrete growth hormone (GH) in episodic bursts every 3.5-4 h. Between the peaks, GH levels are undetectable. In females, GH secretory profiles are characterized as continuous because hormone concentrations are always measurable in the circulation. These gender differences in the circulating GH profiles are responsible, to varying degrees, for observed sexual dimorphisms ranging from body growth to the expression of hepatic cytochrome P450 (P450, CYP) isoforms. Using hypophysectomized rats in which restored gender-dependent plasma GH profiles were manipulated, we have investigated the importance of the interpulse period in the masculine episodic plasma GH profile in regulating expression (mRNA, protein and/or specific catalytic activity) of male-specific CYP2A2, 2C11, 2C13 and 3A2, female-specific CYP2C12 and female-predominant CYP2A1, 2C6 and 2C7. We observed that some isoforms were induced or suppressed by discerning the length of the GH-devoid interpulse period, others responded to the pulse amplitudes, still others recognized the mean circulating concentrations of GH and some were regulated by a combination of these signals. We conclude that concealed in the gender-dependent circulating GH profiles are numerous intrinsic signals, both inductive and repressive, individually "tailored" to be recognized by each isoform of P450. There would appear to be no one signal in each gender-dependent GH profile responsible, in toto, for the characteristic sexually dimorphic expression of some dozen hepatic P450s in male and female rats.