Gender differences in the responsiveness of hepatic calcium oscillator to growth hormone

Abstract

Sexual dimorphisms are encountered at every level, i.e. at the behavioral,anatomic, physiological, biochemical, and molecular. Although many of theimprinting and activational events determining anatomic and behavioral sexualdimorphisms have been defined, the factors that regulate gender differencesexpressed at the molecular level are poorly understood. Rat liver is known to beregulated by the gender-dependent profiles of circulating growth hormone (GH).Male rats secrete GH in episodic burst every 3.5–4 h. Between the peaks, GHlevels are undetectable. In female rats, the hormone pulses are more frequent andirregular and are of lower magnitude than those in males, whereas the interpulseconcentrations of GH are always measurable. Single rat hepatocytes microin-jected with the photoprotein aequorin generate oscillations in the cytosolic freeCa 2+ concentration ([Ca 2+]i) when stimulated with agonists acting through thephosphoinositide signaling pathway. In single male rat hepatocytes phenyleph-rine (Phe) and bovine-GH (bGH) induce [Ca2+ ]i oscillations. We investigatedthe effects of Phe and bGH in single female rat hepatocytes microinjected withaequorin. Both agonists are able to induce [Ca 2+ ]i oscillations in single femalehepatocytes similar to those induced in male hepatocytes. The effect of Phe wasthe previously observed with the same concentration range. However, thethreshold concentration for bGH-induced [Ca 2+]i oscillations is a 10-fold lowerthan in male. This difference in the GH-response could play a role in the sexuallydimorphic expression of hepatic enzymes, such as P450 isoforms, regulated bythe gender-dependent secretory GH profiles.