Ontogeny profile of hepatic phase II enzymes in rats based on metabolic activity, protein expression, and mRNA expression levels
Percentages represent expression/activity relative to adult levels.
| Onset of Activity and/or Expression | Adult Levels Reached | Age-Related Changes in Activity/Expression | Comments | References | ||
|---|---|---|---|---|---|---|
| UGT1A1 | ||||||
| Catalytic activity | −5 days (5%) | 20 days | Increased rapidly | Ontogeny profile established. Adult age: 80 days. Substrates: bilirubin, furosemide. Methods: RLM, RLH. Strain: Wistar (mixed sex), WAG (M) | Wishart (1978); Campbell and Wishart (1980); Rachmel and Hazelton (1986); Coughtrie et al. (1988)) | |
| mRNA expression | −1 day (3%) | >30 days | Inconsistent pattern/increased progressively | Single study, peak (200%) after 1 day. Adult age: 56 days. Methods: qPCR. Strain: Wistar (M) | Kishi et al. (2008) | |
| UGT1A5 | ||||||
| mRNA expression | −5 days (3%) | 0–56 days | Inconsistent pattern/increased rapidly | Single study, peak (300%) after 7 days. Adult age: 56 days. Methods: qPCR. Strain: Wistar (M) | Kishi et al. (2008) | |
| UGT1A6 | ||||||
| Catalytic activity | −2 wk (3%) | 0 days | Inconsistent pattern/increased rapidly | Single study, high resolution, large variability. Adult age: 800 days. Substrates: 2-aminophenol, 1-nitrophenol, 4-nitrophenol. Methods: RLH, RLM, liver snips. Strain: Wistar (mixed), Sprague-Dawley (mixed), WAG (M) | Wishart (1978); Matsui and Watanabe (1982); Scragg et al. (1983); Rachmel and Hazelton (1986); Santa Maria and Machado (1988); Matsumoto et al. (2002); Kishi et al. (2008) | |
| mRNA expression | −5 days (2%) | −0.5 28 days | Inconsistent pattern/increased rapidly | Single study, low resolution. Adult age: 56 days. Methods: qPCR. Strain: Wistar (M) | Kishi et al. (2008) | |
| UGT2B1 | ||||||
| Catalytic activity | −5 days (23%) | 3 wk | Increased progressively | High resolution, nine compounds over 17 data sets. Adult age: 80 days. Substrates: testosterone, androsterone, bisphenol A, nonylphenol, octylphenol, diethylstilbestrol, 4-hydroxybiphenyl, estrone, morphine. Methods: RLM, RLH. Strain: Wistar (mixed), Sprague-Dawley (mixed), WAG (M) | Campbell and Wishart (1980); Matsui and Watanabe (1982); Rachmel and Hazelton (1986); Coughtrie et al. (1988); Matsumoto et al. (2002) | |
| UGT2B2 | ||||||
| mRNA expression | −2 days (3%) | 14 days | Increased rapidly | Single study, semiquantitative, no data after 21 days. Adult age: 21 days. Methods: Northern blot. Strain: Wistar (mixed) | Kishi et al. (2008) | |
| SULT1A1 | ||||||
| Catalytic activity | 2 days (14%) | 40 days | Increased rapidly | Single study, data for high and low sulfation activity were pooled (S.D. provided in graphs). Adult age: 80 days. Fetal development: NR. Substrate: 4-nitrophenol O-sulfation. Methods: RLC. Strain: Wistar (M/F) | Matsui and Watanabe (1982) | |
| mRNA expression | M: 1.5 days (28%); F: 1.5 days (75%) | M: 15 days; F: 7 days | Inconsistent pattern/increased rapidly | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| SULT1B1 | ||||||
| Catalytic activity | M: 2 days (26%); F: 2 days (49%) | 49 days (100%) | Inconsistent pattern/increased slowly | Single study. Adult age: 49 days. Fetal development: NR. Substrate: naphthol O-sulfation. Methods: RLC. Strain: not defined (M/F) | Iwasaki et al. (1994) | |
| SULT1C1 | ||||||
| mRNA expression | M: 1.5 days (5%); F: 1.5 days (46%) | M: 45 days; F: 15 days | M: increased slowly; F: increased rapidly | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| SULT1E1 | ||||||
| mRNA expression | M: 1.5 days (2.5%); F: 1.5 days (35%) | M: 60 days; F: 90 days | M: inconsistent pattern/increase slowly; F: increased rapidly | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| SULT2A1/sult-20/21 | ||||||
| Catalytic activity | M: (25%–300%); F: 2 days (13%–30%) | M: 25–49 days; F: 17 days | M: inconsistent pattern/increased rapidly; F: increased progressively | All substrate data reported by Iwasaki and coworkers (1994) correlate with desipramine sulfation [Tiaramide O-sulfation, Piperazine derivate (DETR) N-sulfation, Aniline N-sulfation, Piperidine derivative (PTHP), N-sulfation, Desipramine N-sulfation). Desipramine sulfation has been associated with SULT2A1. Androsterone sulfation showed a similar variable profile (distinction between high and low activity). Adult age: 49/80 days. Fetal development: NR. Methods: RLC. Strain: Wistar (M/F) and unknown (M/F) | Matsui and Watanabe (1982); Iwasaki et al. (1994) | |
| mRNA expression (SULT-20/21) | M: 1.5 days (25%); F: 1.5 days (8%) | M: 60 days; F: 60 days | Increased slowly | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| Bile-salt sulfotransferase/sult2a1 | ||||||
| Catalytic activity | 2 days (7%) | M: NR; F: NR | Inconsistent pattern | Single study. Adult age: 30 days. Substrate: bile salt mixture. Substrate: unknown. Methods: RLC. Strain: Sprague-Dawley (M/F) | Chen (1982) | |
| 3β-hydroxy-5-cholenoate sulfotransferase (not defined) | ||||||
| Catalytic activity | M: −2 days (5%); F: −2 days (24%) | M: 21 days; F: 0 77 days | M: increased rapidly; F: inconsistent pattern/increased rapidly | Single study, isoform unknown. Adult age: 77 days. Fetal development: NR (F). Substrate: 3β-hydroxy-5-cholenoate. Methods: RLC. Strain: Sprague-Dawley (M/F) | Kane and Chen (1991)) | |
| SULT-40/41/hydroxysteroid sulfotransferase/sult2a6 | ||||||
| mRNA expression | M: NR; F: NR | M: NR; F: NR | M: inconsistent pattern; F: inconsistent pattern | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| SULT-60/hydroxysteroid sulfotransferase/sult2a2 | ||||||
| mRNA expression | M: 1.5 days (50%); F: 1.5 days (1.5%) | M: 0 days; F: 45 days | M: inconsistent pattern/no changes; F: increased slowly | Single study. Adult age: 90 days. Fetal development: NR. Methods: qPCR. Strain: NR (M/F) | Klaassen et al. (1998) | |
| NAT1 | ||||||
| Catalytic activity | NR | NR (195% at −8 days) | No changes | Single study. Adult age: 21 days. Fetal development: NR (−8 days). Substrate: p-amino benzoic acid. Methods: RLC. Strain: CD (Charles River) (M/F) | Lucier et al. (1975) | |
| mRNA expression | 1 day (3%) | 182 days | Increased slowly | Single study. Adult age: 365 days. Fetal development: NR. Methods: qPCR. Strain: F344 (M) and Sprague-Dawley (M) | Hein et al. (2008) | |
| NAT2 | ||||||
| mRNA expression | 1 day (58%) | Variable | No changes | Single study. Adult age: 365 days. Fetal development: NR. Methods: qPCR. Strain: F344 (M) and Sprague-Dawley (M) | Hein et al. (2008) | |
| GST | ||||||
| Catalytic activity | −8 (2%) | 30 days | Increased rapidly | Adult age: 600 days. Substrates: 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-(3-nitrophenoxy)propane, 1-chloro-3,4dinitrobenzene, 3,4_dichloronitrobenzene, bromosulfophthalein, ethacrynic acid, trans-4-phenyl-3-buten-2-one. Methods: RLC. Strain: Wistar (M/F) and Sprague-Dawley (M/F) | Gregus et al. (1985); Tee et al. (1992); Jang et al. (1998); Elbarbry and Alcorn (2009) | |
| GSH peroxidase | ||||||
| Catalytic activity | −3 days (7%) | NR (720 days) | Increased slowly | Adult age: 720 days. Substrate: GSSG reduction coupled to NADPH oxidation; Glutathione peroxidase kit. Methods: RLC, RLH. Strain: Wistar (M/F) and Sprague-Dawley (M) | Santa Maria and Machado (1988); Jang et al. (1998); Elbarbry and Alcorn (2009) | |
| GSH reductase | ||||||
| Catalytic activity | −3 days (30%) | 21 days | Inconsistent pattern | Adult age: 720 days. Fetal development: NR (−3 days). Substrates: NADPH oxidation and GSH reductase kit. Methods: RLH, RLC. Strain: Wistar (M/F) and Sprague-Dawley (M) | Santa Maria and Machado (1988); Elbarbry and Alcorn (2009) | |
F, female; GSSG, glutathione disulfide; M, male; NR, not reported; qPCR, quantitative polymerase chain reaction; RLC, rat liver cytosol; RLH, rat liver homogenate; RLM, rat liver microsome.