Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-04T18:19:04.658Z Has data issue: false hasContentIssue false
  • English
  • Français

Concomitant changes in progesterone catabolic enzymes, cytochrome P450 2C and 3A, with plasma insulin concentrations in ewes supplemented with sodium acetate or sodium propionate*

Published online by Cambridge University Press:  01 August 2008

C. O. Lemley ,
J. M. Koch ,
K. P. Blemings ,
K. M. Krause  and
M. E. Wilson
C. O. Lemley
Affiliation:
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506-6108, USA
J. M. Koch
Affiliation:
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506-6108, USA
K. P. Blemings
Affiliation:
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506-6108, USA
K. M. Krause
Affiliation:
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506-6108, USA
M. E. Wilson*
Affiliation:
Division of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506-6108, USA
*
E-mail: [email protected]
Get access

Abstract

Progesterone is essential for maintaining pregnancy, and several authors have suggested that low peripheral concentrations of progesterone may be responsible for high rates of embryonic loss. The primary organ involved in the catabolism of progesterone is the liver, and cytochrome P450 2C and 3A sub-families account for a large proportion of this catabolism. Elucidating a mechanism to decrease progesterone catabolism, thereby increasing embryonic and uterine exposure to progesterone, seems a logical approach to ameliorate high rates of embryonic loss. The objectives of the current experiment were to determine the pattern of insulin secretion after supplementing feed with either sodium acetate or sodium propionate and to determine any association between the differential patterns of insulin secretion with the hepatic activity of cytochrome P450 2C and 3A and progesterone clearance. Sixteen ovariectomized ewes were fed 3 kg/day for 10 days of a diet consisting of 50% corn silage, 38% triticale haylage, 12% soybean meal and 600 ml of 3.5 M sodium acetate (energy control; n = 8) or 2.0 M sodium propionate (gluconeogenic substrate; n = 8). Equal portions of the ration (1 kg as-fed basis along with 200 ml of 3.5 M sodium acetate or 2.0 M sodium propionate) were offered three times daily at 0600, 1400 and 2200 h. Concentrations of insulin in plasma were determined immediately before feeding and at 15, 30, 60, 90, 120, 180, 240 and 300 min after feeding. Progesterone clearance from peripheral circulation (ng/ml per min) was measured by giving a 5 mg injection of progesterone into the left jugular vein and collecting blood via the right jugular vein at 0, 2, 4, 6, 8, 10, 15, 20 and 30 min afterwards. Liver biopsies were taken 1 h after feeding to determine cytochrome P450 2C and 3A activities. Insulin concentrations in ewes supplemented with sodium propionate were elevated at 15, 30 and 60 min after feeding compared to the sodium acetate group. Cytochrome P450 2C and 3A activities were decreased 1 h after feeding in the sodium propionate-treated ewes relative to sodium acetate. Insulin appears to down-regulate cytochrome P450 activity, which could be used to decrease the catabolism of progesterone during early gestation, thereby increasing peripheral concentrations of progesterone and, consequently, embryonic exposure to progesterone.

Keywords

progesterone catabolismsheepinsulincytochrome P450
Type
Full Paper
Information
animal , Volume 2 , Issue 8 , August 2008 , pp. 1223 - 1229
Copyright
Copyright © The Animal Consortium 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

This work is published with the approval of the Director of West Virginia Agriculture and Forestry Experiment Station as scientific paper 3002. This project was supported by Hatch project 468 (NE 1007).

References

Al-Busadah, KA, Homeida, AM 2004. Pharmacokinetics of progesterone in dromedary camels (Camelus dromedarim). Research in Veterinary Science 77, 245–247.CrossRefGoogle ScholarPubMed
Barnett, CR, Gibson, GG, Wolf, CR, Flatt, PR, Ioannides, C 1990. Induction of cytochrome P450III and P450IV family proteins in streptozotocin-induced diabetes. Biochemical Journal 268, 765–769.CrossRefGoogle ScholarPubMed
Bedford, CA, Harrison, FA, Heap, FB 1972. The metabolic clearance rate and production rate of progesterone and the conversion of progesterone to 20-alpha-hydroxypregn-4-en-3-one in the sheep. Journal of Endocrinology 55, 105–118.CrossRefGoogle Scholar
Bedford, CA, Harrison, FA, Heap, FB 1974. Splanchnic, uterine, ovarian and adrenal uptake of progesterone and 20-alpha-hydroxyprogesterone in the pregnant and non-pregnant sheep. Journal of Endocrinology 62, 277–290.CrossRefGoogle ScholarPubMed
Bidstrup, TB, Bjornsdottir, I, Sidelmann, UG, Thomsen, MS, Hansen, KT 2003. CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. British Journal of Clinical Pharmacology 56, 305–314.CrossRefGoogle Scholar
Bork, RW, Muto, T, Beaune, PH, Srivastava, PK, Lloyd, RS, Guengerich, FP 1989. Characterization of mRNA species related to human liver cytochrome P450 nifedipine oxidase and the regulation of catalytic activity. Journal of Biological Chemistry 264, 910–919.CrossRefGoogle ScholarPubMed
Dean, ME, Stock, BH 1975. Hepatic microsomal metabolism of drugs during pregnancy in the rat. Drug Metabolism and Disposition 3, 325–331.Google ScholarPubMed
Dixon, AB, Knights, M, Winkler, JL, Marsh, DJ, Pate, JL, Wilson, ME, Dailey, RA, Siedel, G, Inskeep, EK 2007. Patterns of late embryonic and fetal mortality and association with several factors in sheep. Journal of Animal Science 85, 1274–1284.CrossRefGoogle ScholarPubMed
Guengerich, FP, Martin, MV, Beaune, PH, Dremers, P, Wolff, T, Waxman, DJ 1986. Characterization of rat and human liver microsomal cytochrome P450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. Journal of Biological Chemistry 261, 5051–5060.CrossRefGoogle ScholarPubMed
Gurpide, E 1975. Tracer Methods in Hormone Research: Monographs on Endocrinology. Springer-Verlag, New York, NY.CrossRefGoogle Scholar
Larson, SF, Butler, WR, Currie, WB 2007. Pregnancy rates in lactating dairy cattle following supplementation of progesterone after artificial insemination. Animal Reproduction Science 102, 172–179.CrossRefGoogle ScholarPubMed
Lemley, CO, Butler, ST, Butler, WR, Wilson, ME 2008. Short communication: insulin alters hepatic progesterone catabolic enzymes, cytochrome P450 2C and 3A, in dairy cows. Journal of Dairy Science 91, 641–645.CrossRefGoogle ScholarPubMed
Li, XQ, Weidolf, L, Simonsson, R, Andersson, TB 2005. Enantiomer/enantiomer interactions between the S- and R-isomers of omeprazole in human cytochrome P450 enzymes: major role of CYP2C19 and CYP3A4. Journal of Pharmacology and Experimental Therapeutics 315, 777–787.CrossRefGoogle Scholar
McDonald, LE, Nichols, RE, McNutt, SH 1952. Studies on corpus luteum ablation and progesterone replacement therapy during pregnancy in the cow. American Journal of Veterinary Research 13, 446–451.Google ScholarPubMed
Miller, WR, Williams, R, Pipes, GW, Turner, CW 1963. Conjugation, distribution, and biological half-life (t 1/2) of radioactive progesterone in plasma and red cells of bovine blood. Journal of Dairy Science 46, 1402–1404.CrossRefGoogle Scholar
Murray, M 1991. Microsomal cytochrome P450-dependent steroid metabolism in male sheep liver. Quantitative importance of 6β-hydroxylation and evidence for the involvement of a P450 from the IIIA subfamily in the pathway. Journal of Steroid Biochemistry and Molecular Biology 38, 611–619.CrossRefGoogle Scholar
Murray, M 1992. Participation of a cytochrome P450 enzyme from the 2C subfamily in progesterone 21-hydroxylation in sheep liver. Journal of Steroid Biochemistry and Molecular Biology 43, 591–593.CrossRefGoogle ScholarPubMed
Navarre, CB, Pugh, DG 2002. Diseases of the gastrointestinal system. In Sheep and goat medicine (ed. DG Pugh), p. 73. W. B. Saunders Company, Philadelphia, PA.Google Scholar
Nelson, AC, Huang, W, Moody, DE 2001. Variables in human liver microsome preparation: Impact on the kinetics of L-alpha-acetylmethadol (LAAM) N-demethylation and dextromethorphan O-demethylation. Drug Metabolism and Disposition 29, 319–325.Google ScholarPubMed
Parr, RA, Davis, IF, Miles, MA, Squires, TJ 1993. Feed intake affects metabolic clearance rate of progesterone in sheep. Research in Veterinary Science 55, 306–310.CrossRefGoogle ScholarPubMed
Robinson, NA, Leslie, KE, Walton, JS 1989. Effect of treatment with progesterone on pregnancy rate and plasma concentrations of progesterone in Holstein cows. Journal of Dairy Science 72, 202–207.CrossRefGoogle ScholarPubMed
Ryan, DE, Levin, W 1990. Purification and characterization of hepatic microsomal cytochrome P-450. Pharmacology and Therapeutics 45, 153–239.CrossRefGoogle ScholarPubMed
Saad, B, Thomas, H, Schawalder, H, Waechter, F, Maier, P 1994. Oxygen tension, insulin, and glucagon affect the preservation and induction of cytochrome P450 isoforms in cultured rat hepatocytes. Toxicology and Applied Pharmacology 126, 372–379.CrossRefGoogle ScholarPubMed
Sangsritavong, S, Combs, DK, Sartori, R, Armentano, LE, Wiltbank, MC 2002. High feed intake increases liver blood flow and metabolism of progesterone and estradiol-17beta in dairy cattle. Journal of Dairy Science 85, 2831–2842.CrossRefGoogle ScholarPubMed
Selvaraju, S, Agarwal, SK, Karche, SD, Srivastava, SK, Majumdar, AC, Shanker, U 2002. Fertility responses and hormonal profiles in repeat breeding cows treated with insulin. Animal Reproduction Science 73, 141–149.CrossRefGoogle ScholarPubMed
Sheffel, CE, Pratt, BR, Ferrell, WL, Inskeep, EK 1982. Induced corpora lutea in the postpartum beef cow. II. Effects of treatment with progestogen and gonadotropins. Journal of Animal Science 54, 830–836.CrossRefGoogle ScholarPubMed
Shimojo, N, Ishizaki, T, Imaoka, S, Junae, Y, Fujii, S, Okuda, K 1993. Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes. Biochemical Pharmacology 46, 621–627.CrossRefGoogle ScholarPubMed
Sidhu, JS, Omiecinski, CJ 1999. Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures. Journal of Biochemical and Molecular Toxicology 13, 1–9.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Smith, DL, Stinefelt, BM, Blemings, KP, Wilson, ME 2006. Diet-induced alterations in progesterone clearance appear to be mediated by insulin signaling in hepatocytes. Journal of Animal Science 84, 1102–1109.CrossRefGoogle ScholarPubMed
Starbuck, MJ, Dailey, RA, Inskeep, EK 2004. Factors affecting retention of early pregnancy in dairy cattle. Animal Reproduction Science 84, 27–39.CrossRefGoogle ScholarPubMed
Stevenson, JS, Mee, MO 1991. Pregnancy rates of Holstein cows after postinsemination treatment with a progesterone-releasing intravaginal device. Journal of Dairy Science 74, 3849–3856.CrossRefGoogle ScholarPubMed
Waxman, DJ, Lapenson, DP, Aoyama, T, Gelboin, HV, Gonzalez, FJ, Korzekwa, K 1991. Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Archives of Biochemistry and Biophysics 290, 160–166.CrossRefGoogle ScholarPubMed
Woodcroft, KJ, Novak, RF 1999. Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP) 2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes. Journal of Pharmacology and Experimental Therapeutics 289, 1121–1127.Google ScholarPubMed
You, L 2004. Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes. Chemico-Biological Interactions 147, 233–246.CrossRefGoogle ScholarPubMed
Yuan, R, Madani, S, Wei, X, Reynolds, K, Huang, S 2002. Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metabolism and Disposition 30, 1311–1319.CrossRefGoogle ScholarPubMed