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

Abstract

Two experiments were performed to determine the effects of heat stress (HS) and insulin on hepatic mRNA abundance of enzymes responsible for metabolizing progesterone [cytochrome P450 2C and 3A (CYP2C and CYP3A)]. To distinguish the direct effects of HS from decreased dry matter intake, cohorts were pair fed (PF) in thermoneutral conditions to match the intake of the HS cows during both experiments. In the first experiment, multiparous late-lactation Holstein cows (n=12, 305±33 d in milk) housed in climate-controlled chambers were subjected to 2 experimental periods: (1) thermoneutral (TN) conditions (18°C, 20% humidity) with ad libitum intake (TN and well fed) for 9 d; and (2) either HS conditions (cyclical temperature 31-40°C, 20% humidity) fed for ad libitum intake (n=6), or TN conditions and PF to match the HS animal (n=6) for 9 d. To evaluate hepatic gene expression during experiment 1, biopsies were obtained at the end of each period. In the second experiment, multiparous mid-lactation Holstein cows (n=12, 136±8 DIM) were housed and fed in conditions similar to those described for the first experiment. Liver biopsies were obtained immediately before and after an insulin tolerance test administered on d 6 of each period. No effects of exogenous insulin were observed on any of the tested variables, nor were there interactions between environment (TN/HS or well fed/PF) and insulin administration. Heat stress decreased hepatic CYP2C expression during both experiments. The relative abundance of CYP3A was not affected by environmental conditions in the late-lactation cows (first experiment), but was reduced by HS in the mid-lactation cows (second experiment). Interestingly, during experiment 2, hepatic CYP3A expression also decreased during PF. These results suggest that HS reduces the capacity of the liver to metabolize progesterone through distinct effects on CYP2C and CYP3A, and that the effects appear to vary based upon stage of lactation. Ultimately, HS may affect reproductive outcomes by reducing the abundance of the enzymes responsible for the breakdown of progesterone. This reduction could serve as a beneficial adaptation for rescuing early embryos or may be detrimental, as it affects feedback mechanisms necessary for proper cyclicity.

Deep Transcriptomic Analysis of Black Rockfish (Sebastes schlegelii) Provides New Insights on Responses to Acute Temperature Stress

“…Cytochrome P450 ( CYP ) is a superfamily containing a series of genes encoding P450 enzymes and are found in all aerobic eukaryotes and other vertebrates 55 , 56 . In a study on the cytochrome p450 metabolic enzymes in cows under heat stress conditions, the relative abundances of CYP2C and CYP3A were found to be decreased 57 . A study on Symbiodinium under both rapid and gradual thermal stress revealed that up-regulation occurred under gradual heat stress before the maximum temperature was reached, and down-regulation occurred under rapid stress and gradual stress after the maximum temperature was reached 58 .…”

Impacts of chronic and increasing lipopolysaccharide exposure on production and reproductive parameters in lactating Holstein dairy cows

“…Sequences for TLR4, REL associated protein of NFκB (RELA), acyloxyacyl hydrolase (AOAH), and LBP were designed via NCBI primer blast (https: / / www .ncbi .nlm .nih .gov/ tools/ primer -blast/ ), all spanned at least 1 exon junction, and are detailed in Table 2. Sequences for cytochrome P450 family 2 subfamily C (CYP2C), cytochrome P450 family 3 subfamily A (CYP3A), and ribosomal protein 15 (RPS15) were from McCracken et al (2015). Each set of reactions was performed to include negative controls of water only, as well as cDNA with Mastermix (Thermo Fisher Scientific) and omission of primers.…”

Evaluation of DNA methylation and mRNA expression of heat shock proteins in thermal manipulated chicken

“…Another enzyme, cytochrome p450, which is responsible for synthesizing various hormones including progesterone, was upregulated in the TC group embryos. McCracken et al (2015) suggested that adverse reproductive outcomes may be encountered due to heat stress because of the reduction of enzymes essential for progesterone breakdown. The decreased mRNA expression of cytochrome p450 in heat-stressed laying hens may affect their ovaries (Rozenboim et al 2007).…”