Abstract

Our recent study carried out after local injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the arcuate nuclei (ARC) of the hypothalamus suggested a positive influence of the serotonergic innervation of the ARC on growth hormone secretion and growth hormone-dependent expression of cytochrome P450. The aim of our present study was to determine the effect of the activation of the 5-HT1 or 5-HT2 type receptors in the ARC on the expression and activity of cytochrome P450 in the liver of male rats. The serotonergic agonists 5-CT (5-carboxyamidotryptamine, a 5-HT1 type receptor agonist) or DOI (2,5-dimethoxy-4-iodoamphetamine, a 5-HT2 type receptor agonist) were injected into the ARC for 5 days. The activity and expression of cytochrome P450 isoenzymes and the levels of serum and pituitary hormones were estimated. DOI significantly increased the activity and expression (both mRNA and protein levels) of CYP2C11, CYP3A1/23 and CYP3A2, which positively correlated with an increase in the pituitary GHRH and serum growth hormone level. The injection of 5-CT into the ARC did not affect the activity of liver CYP isoenzymes or hormone levels. The obtained results indicate that 5-HT2, but not the 5-HT1 type receptors in the ARC, are engaged in the positive neuroendocrine regulation of cytochrome P450, possibly by the stimulation of hypothalamic GHRH release and pituitary GH secretion, and an increase in the serum growth hormone concentration. Further studies are going to identify which of the 5-HT2 receptor subtypes (5-HT2A, 5-HT2B or 5-HT2C) is responsible for the observed neuroendocrine regulation of cytochrome P450.