Expression of hepatic and ovarian cytochrome P450 during estrous cycle in rats

Abstract

It is known that gender differences in drug metabolism are largely attributed to changes in sex and growth hormones. Serum concentrations of estradiol, progesterone, prolactin, follicle-stimulating hormone, and luteinizing hormone change markedly during the human menstrual cycle and the rat estrous cycle. However, little information is available regarding the effects of the human menstrual cycle or the rat estrous cycle on expression and activity of cytochrome P450 (CYP) isoforms. The present study was carried out to determine the expression and activity of CYP-dependent drug-metabolizing enzymes in the liver and ovary during the estrous cycle. The expression and activity of microsomal CYP isoforms (CYP1A1, CYP1A2, CYP1B1, CYP2B1, CYP2C11, CYP2C12, CYP2E1, CYP3A1, CYP3A2, and CYP4A), cytochrome b(5) and NADPH-dependent CYP reductase in the liver and ovary were measured in female rats in diestrus and proestrus. Our results indicated that hepatic and ovarian expression and activity of CYP isoforms, cytochrome b(5), and NADPH-dependent CYP reductase were not different between diestrus and proestrus, although serum estradiol concentration and uterus weight were markedly increased in the proestrus phase. These results suggest that the cytochrome P450-dependent system is not sensitive to changes in the estrous cycle, and further studies are warranted to determine the effects of the estrous cycle on in vivo metabolism of xenobiotics.

Prolactin Upregulates Female-PredominantP450Gene Expressions and Downregulates Male-Predominant Gene Expressions in Mouse Liver

“…Prior studies have reported that a proestrous surge of prolactin did not change hepatic P450 expression and Stat5 activity, and that neither ablation of prolactin by bromocriptine nor direct injection of prolactin affected hepatic Stat5 activity (Choi and Waxman, 1999;Lee et al, 2012). Considering the short duration of proestrous prolactin surge, which consists of 2 hours of an early peak (350-550 ng/ml) and a following 4 hours of a lower plateau (250-300 ng/ml) (Murai et al, 1989), and the rapid metabolic clearance of prolactin in the rat, in which half-life time of prolactin was 3.9-5.2 minutes (Koch et al, 1971), or in the human (Sievertsen et al, 1980), it is not contradictory that a proestrous surge of prolactin or direct injection of prolactin, as well as a continuous basal level of prolactin that could be ablated by bromocriptine, did not influence the upregulation of expression of femalepredominant P450 genes or Stat5 activation in the liver.…”

Immunohistological expression of cytochrome P450 1A2 (CYP1A2) in the ovarian follicles of prepubertal and pubertal rat

“…Furthermore, it primarily metabolizes endogenous hormones with respect to progesterone to 6β-hydroxyl progesterone by hydroxylation, estrone to 2-or 4-hydroxyestrone by hydrolysis and estradiol to estriol by hydroxylation in humans (Mikhailova et al, 2006;Sugiyama et al, 2019;Lu et al, 2020). CYP1A subfamily contains only two functional isoforms as CYP1A1 and CY-P1A2, and it has been addressed that CYP1A2 is expressed mainly in the liver; whereas the expression of CYP1A1 is mainly distributed outside the liver and involves the metabolism for aromatic hydrocarbon, CYP1A2 is expressed in the liver and metabolizes the aromatic amines and heterocyclic compounds (Wijnen et al, 2007;Lee et al, 2012;Lu et al, 2020). However, in recent days, the expression of CYP1A2 is identified in the pancreas and lung as well (Vukovic et al, 2016).…”

Short communication: Hepatic progesterone-metabolizing enzymes cytochrome P450 2C and 3A in lactating cows during thermoneutral and heat stress conditions

“…Pregnancy was not confirmed before sample collection because cows would have only been in early pregnancy. At this stage, pregnancy is not expected to affect expression of the genes of interest, and previous experiments in rats indicate that hepatic mRNA concentrations from the CYP genes are not sensitive to changes in the estrous cycle (Lee et al, 2012). The HS environment differed only slightly from the first experiment (31-39°C, 20% humidity: minimum THI = 73, maximum THI = 80.5), whereas the PF animals remained in a constant environment of 20°C.…”