Infusion of gender-dependent plasma growth hormone profiles into intact rats: effects of subcutaneous, intraperitoneal, and intravenous routes of rat and human growth hormone on endogenous circulating growth hormone profiles and expression of sexually dimorphic hepatic cyp isoforms

Abstract

The dramatic sexual dimorphism in rat hepatic CYPs is determined by gender differences in the circulating GH profiles. Accordingly, each responsive isoform of CYP is induced or suppressed by different components, i.e., signaling elements, in the GH profiles. It was the purpose of this study to determine whether the signaling elements in the sexually dimorphic plasma GH profiles identified in GH-depleted rats are recognized by the hepatic CYPs in intact rats exposed to a multiplicity of signals contained in the normal gender-dependent GH profiles. To accomplish this goal, we imposed (via osmotic minipumps) the continuous feminine GH profile upon normal male rats and superimposed (via intra-atrial catheters) the episodic masculine profile upon normal females. Monitored circulating GH profiles indicated that the administered GH had little or no effect on the normally secreted gender-dependent endogenous profiles. Basically, we observed that the degree of constancy of GH in the circulation (continuous in females and episodic in males) is the primary determinant establishing sexually dimorphic expression of eight hepatic CYPs in intact rats. However, the characteristic expression levels of each isoform observed in male and female rat liver are determined by an interaction of more subtle signals in the GH profiles reflected in the concentration and persistence of the feminine continuous profile as well as the frequency, duration, and amplitude of pulse and interpulse periods in the masculine episodic profile. In the course of the study, unexpected findings led us to compare the effectiveness of s.c.- and i.p.-infused GH and rGH with hGH. Briefly, male- and female-dependent hepatic CYPs were undoubtedly most responsive to rGH infused by i.p.-implanted osmotic pumps.