Article Figures & Data
Figures
- Fig. 1.
The effect of the repeated injection of the 5-HT1 receptor agonist 5-CT (A) and the 5-HT2 receptor agonist DOI (B) into the ARC (5 or 3 μg/side, respectively) on different cytochrome P450 isoenzyme activities, measured as the rates of cytochrome P450 enzyme-specific reactions in rat liver microsomes: testosterone 7α- (CYP2A), 16β- (CYP2B), 2α- and 16α- (CYP2C11), and 2β- and 6β- (CYP3A) hydroxylation and caffeine 8-hydroxylation and 3-N-demethylation (CYP1A). All values are shown as the mean ± S.E.M. (n = 8–10). Statistical significance was assessed by one-way analysis of variance followed by Duncan’s test, and is indicated as *P < 0.05; **P < 0.01, compared with the control. The control values (picomoles per milligram protein per minute) are as follows for A and B: 154.8 ± 10.4, 219.1 ± 35.0, 431.4 ± 36.9, 315.1 ± 61.4, 253.6 ± 23.9, and 810.3 ± 97.5 (testosterone 7α-, 16β-, 2α-, 16α-, 2β-, and 6β-hydroxylation, respectively), and 2.1 ± 0.1 (caffeine 8-hydroxylation), 16.0 ± 1.2 (caffeine 3-N-demethylation) for the ARC of the hypothalamus.
- Fig. 2.
The effect of repeated injection of the 5-HT2 receptor agonist DOI into the ARC (3 μg/side) on the protein level of CYP2C11, CYP3A1/23, and CYP3A2 enzymes in rat liver microsomes. Microsomal proteins, 10 μg, were subjected to western immunoblot analysis. The presented results are representative blots from four (for the control and DOI) separate rats per treatment (A). The data are expressed as the mean ± S.E.M. (n = 6–8) (B). Statistical significance was assessed by Student’s t test and is indicated as *P < 0.05, compared with the control.
- Fig. 3.
The effect of repeated injections of the 5-HT1 receptor agonist 5-CT (A) and 5-HT2 receptor agonist DOI (B) into the ARC (5 or 3 μg/side, respectively) on the pituitary GHRH level and serum hormone concentrations. All values are presented as the mean ± S.E.M. (n = 6–9). Statistical significance was assessed by one-way analysis of variance followed by Duncan’s test and is indicated as *P < 0.05 compared with the control. The absolute control values for 5-CT and DOI were 2.9 ± 1.1, 140.8 ± 19.5, 6.7 ± 0.15, and 73.5 ± 1.8 ng/ml, and 25.6 ± 1.1 pg/mg of the tissue for serum GH, corticosterone (CRT), T3, T4, and GHRH in the pituitary, respectively.
- Fig. 4.
Neuroendocrine regulation of liver cytochrome P450 by serotonergic receptor of the 5-HT2 type located in the ARC (the scheme depicts the results presented in this work). The activation of the 5-HT2-type receptor in the ARC of the hypothalamus stimulates GHRH release and thus pituitary GH secretion, which may lead to increased expression and activity of the GH-dependent CYP2C11, CYP3A1/23, and CYP3A2 enzymes in the liver.
Tables
- TABLE 1
The effect of repeated injection of the 5-HT2 receptor agonist DOI into the ARC (3 μg/side) on the mRNA expression level of CYP2C11, CYP3A1/23, and CYP3A2 genes in rat liver
The results are expressed as the fold change in relation to two housekeeping genes, i.e., HPRT1 and GAPDH. All of the values are shown as the mean fold change (±S.E.M.) calculated by the comparative 2−∆∆Ct method for the control (n = 6–8) and agonist-treated (n = 6 to 7) groups. Statistical significance was assessed by Student’s t test and is indicated as P < 0.05; P < 0.01, compared with the control.
Gene Name HPRT1 Gene GAPDH Gene Fold Change Statistical Significance Fold Change Statistical Significance CYP2C11 1.71 ↑ (±0.18) P < 0.05 1.60 ↑ (±0.16) P < 0.05 CYP3A1/23 2.60 ↑ (±0.87) P = 0.228 2.76 ↑ (±0.50) P < 0.05 CYP3A2 4.06 ↑ (±0.91) P < 0.05 4.49 ↑ (±1.19) P < 0.01
Data Supplement
- Supplemental Figure 1 -
The effect of the repeated injection of the 5-HT1 receptor agonist 5-CT into the ARC (5 μg/side) on the protein level of CYP2C11, CYP3A1/23 and CYP3A2 isoenzymes in rat liver microsomes
- Supplemental Figure 1 -
