Skip to main content
Erschienen in: Digestive Diseases and Sciences 7/2022

24.06.2021 | Original Article

Ovariectomy Affects Acute Pancreatitis in Mice

verfasst von: Melinda Wang, Fred Gorelick

Erschienen in: Digestive Diseases and Sciences | Ausgabe 7/2022

Einloggen, um Zugang zu erhalten

Abstract

Background

Serum estradiol levels in severe acute injury are correlated with in hospital mortality. In acute pancreatitis, serum estradiol levels are strong predictors of disease severity. Studies of whether changes in estradiol levels play a causative role in acute pancreatitis severity are limited. The ovariectomized mouse model has been used to study the effects of estradiol in health and disease.

Aims

We assessed whether the ovariectomized mouse model could be used to assess the effects of estradiol on pancreatitis severity.

Methods

C57BL/6 mice with their ovaries removed were used to simulate low circulating estradiol conditions. Ovariectomized mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis and compared to ovariectomized mice pre-treated with subcutaneous estradiol injections.

Results

Findings suggest ovariectomized model is a problematic preparation to study pancreatitis. At baseline, ovariectomy leads to prominent acinar cell ultrastructure changes as well as changes in other select morphologic and biomarkers of pancreatitis. In addition, ovariectomy changed select acute pancreatitis responses that were only partially rescued by estradiol pre-treatment.

Conclusions

These findings suggest that the ovariectomized mouse as a model of estradiol depletion should be used with caution in pancreatic studies. Future studies should explore whether derangements in other female hormones produced by the ovaries can lead to changes in pancreatic studies.
Literatur
1.
Zurück zum Zitat Dossett LA, Swenson BR, Evans HL, Bonatti H, Sawyer RG, May AK. Serum estradiol concentration as a predictor of death in critically ill and injured adults. Surg Infect. 2008;9:41–48.CrossRef Dossett LA, Swenson BR, Evans HL, Bonatti H, Sawyer RG, May AK. Serum estradiol concentration as a predictor of death in critically ill and injured adults. Surg Infect. 2008;9:41–48.CrossRef
2.
Zurück zum Zitat Kauffmann RM, Norris PR, Jenkins JM, Dupont WD, Torres RE, Blume JD et al. Trends in estradiol during critical illness are associated with mortality independent of admission estradiol. J Am Coll Surg. 2011;212:703–712.CrossRef Kauffmann RM, Norris PR, Jenkins JM, Dupont WD, Torres RE, Blume JD et al. Trends in estradiol during critical illness are associated with mortality independent of admission estradiol. J Am Coll Surg. 2011;212:703–712.CrossRef
3.
Zurück zum Zitat Kumar RG, DiSanto D, Awan N, Vaughan LE, Levochkina MS, Weppner JL, et al. Temporal acute serum estradiol and tumor necrosis factor-α associations and risk of death after severe traumatic brain injury. J Neurotrauma. 2020;37:2198–2210. Kumar RG, DiSanto D, Awan N, Vaughan LE, Levochkina MS, Weppner JL, et al. Temporal acute serum estradiol and tumor necrosis factor-α associations and risk of death after severe traumatic brain injury. J Neurotrauma. 2020;37:2198–2210.
4.
Zurück zum Zitat Pappa T, Vemmos K, Mantzou E, Savvari P, Stamatelopoulos K, Alevizaki M. Estradiol levels predict short-term adverse health outcomes in postmenopausal acute stroke women. Eur J Neurol. 2012;19:1300–1304.CrossRef Pappa T, Vemmos K, Mantzou E, Savvari P, Stamatelopoulos K, Alevizaki M. Estradiol levels predict short-term adverse health outcomes in postmenopausal acute stroke women. Eur J Neurol. 2012;19:1300–1304.CrossRef
5.
Zurück zum Zitat Mauvais-Jarvis F, Klein SL, Levin ER. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. 2020;161:bqaa127.CrossRef Mauvais-Jarvis F, Klein SL, Levin ER. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. 2020;161:bqaa127.CrossRef
6.
Zurück zum Zitat Lu C-W, Liu L-C, Hsieh Y-C, Yang L-H, Chen R-J, Hsieh C-H. Increased admission serum estradiol level is correlated with high mortality in patients with severe acute pancreatitis. J Gastroenterol. 2013;48:374–381.CrossRef Lu C-W, Liu L-C, Hsieh Y-C, Yang L-H, Chen R-J, Hsieh C-H. Increased admission serum estradiol level is correlated with high mortality in patients with severe acute pancreatitis. J Gastroenterol. 2013;48:374–381.CrossRef
7.
Zurück zum Zitat Staubli SM, Oertli D, Nebiker CA. Laboratory markers predicting severity of acute pancreatitis. Crit Rev Clin Lab Sci. 2015;52:273–283.CrossRef Staubli SM, Oertli D, Nebiker CA. Laboratory markers predicting severity of acute pancreatitis. Crit Rev Clin Lab Sci. 2015;52:273–283.CrossRef
8.
Zurück zum Zitat Castro MR, Nguyen TT, O'Brien T. Clomiphene-induced severe hypertriglyceridemia and pancreatitis. In Mayo Clinic Proceedings. Vol. 74. Elsevier; 1999, pp. 1125-1128. Castro MR, Nguyen TT, O'Brien T. Clomiphene-induced severe hypertriglyceridemia and pancreatitis. In Mayo Clinic Proceedings. Vol. 74. Elsevier; 1999, pp. 1125-1128.
9.
Zurück zum Zitat Rao K, Eagon P, Okamura K, Van Thiel D, Gavaler J, Kelly R et al. Acute hemorrhagic pancreatic necrosis in mice. Induction in male mice treated with estradiol. Am J Pathol. 1982;109:8.PubMedPubMedCentral Rao K, Eagon P, Okamura K, Van Thiel D, Gavaler J, Kelly R et al. Acute hemorrhagic pancreatic necrosis in mice. Induction in male mice treated with estradiol. Am J Pathol. 1982;109:8.PubMedPubMedCentral
10.
Zurück zum Zitat Camporez JPG, Jornayvaz FR, Lee H-Y, Kanda S, Guigni BA, Kahn M et al. Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance. Endocrinology. 2013;154:1021–1028.CrossRef Camporez JPG, Jornayvaz FR, Lee H-Y, Kanda S, Guigni BA, Kahn M et al. Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance. Endocrinology. 2013;154:1021–1028.CrossRef
11.
Zurück zum Zitat Hou Y, Wei H, Luo Y, Liu G. Modulating expression of brain heat shock proteins by estrogen in ovariectomized mice model of aging. Exp Gerontol. 2010;45:323–330.CrossRef Hou Y, Wei H, Luo Y, Liu G. Modulating expression of brain heat shock proteins by estrogen in ovariectomized mice model of aging. Exp Gerontol. 2010;45:323–330.CrossRef
12.
Zurück zum Zitat Ohlsson C, Engdahl C, Fåk F, Andersson A, Windahl SH, Farman HH et al. Probiotics protect mice from ovariectomy-induced cortical bone loss. PloS One. 2014;9:e92368.CrossRef Ohlsson C, Engdahl C, Fåk F, Andersson A, Windahl SH, Farman HH et al. Probiotics protect mice from ovariectomy-induced cortical bone loss. PloS One. 2014;9:e92368.CrossRef
13.
Zurück zum Zitat Sniekers Y, Weinans H, Bierma-Zeinstra S, Van Leeuwen J, Van Osch G. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment–a systematic approach. Osteoarthr Cartil. 2008;16:533–541.CrossRef Sniekers Y, Weinans H, Bierma-Zeinstra S, Van Leeuwen J, Van Osch G. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment–a systematic approach. Osteoarthr Cartil. 2008;16:533–541.CrossRef
14.
Zurück zum Zitat Turner RT, Maran A, Lotinun S, Hefferan T, Evans GL, Zhang M et al. Animal models for osteoporosis. Rev Endocr Metab Disord. 2001;2:117.CrossRef Turner RT, Maran A, Lotinun S, Hefferan T, Evans GL, Zhang M et al. Animal models for osteoporosis. Rev Endocr Metab Disord. 2001;2:117.CrossRef
15.
Zurück zum Zitat Kolodecik TR, Reed AM, Date K, Shugrue CA, Patel V, Chung S-L et al. The serum protein renalase reduces injury in experimental pancreatitis. J Biol Chem. 2017;292:21047–21059.CrossRef Kolodecik TR, Reed AM, Date K, Shugrue CA, Patel V, Chung S-L et al. The serum protein renalase reduces injury in experimental pancreatitis. J Biol Chem. 2017;292:21047–21059.CrossRef
16.
Zurück zum Zitat Wu L, Cai B, Zheng S, Liu X, Cai H, Li H. Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis. Inflammation. 2013;36:1020–1029.CrossRef Wu L, Cai B, Zheng S, Liu X, Cai H, Li H. Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis. Inflammation. 2013;36:1020–1029.CrossRef
17.
Zurück zum Zitat García ME, Borelli MI, Dumm CG, Gagliardino J, de Gagliardino EE. Functional and ultrastructural changes induced by short term ovariectomy on pancreatic islets. Hormone Metab Res. 1983;15:76–81.CrossRef García ME, Borelli MI, Dumm CG, Gagliardino J, de Gagliardino EE. Functional and ultrastructural changes induced by short term ovariectomy on pancreatic islets. Hormone Metab Res. 1983;15:76–81.CrossRef
18.
Zurück zum Zitat Bhatia M. Apoptosis versus necrosis in acute pancreatitis. Am J Physiology-Gastrointest Liver Physiol. 2004;286:G189–G196.CrossRef Bhatia M. Apoptosis versus necrosis in acute pancreatitis. Am J Physiology-Gastrointest Liver Physiol. 2004;286:G189–G196.CrossRef
19.
Zurück zum Zitat Jie L, Liu X, Min W, Guo X, Zhan X. Changes of zymophagy during cell model of caerulein-induced experimental acute pancreatitis. Chin J Digest. 2014;34:752–755. Jie L, Liu X, Min W, Guo X, Zhan X. Changes of zymophagy during cell model of caerulein-induced experimental acute pancreatitis. Chin J Digest. 2014;34:752–755.
20.
Zurück zum Zitat Sah RP, Saluja A. Molecular mechanisms of pancreatic injury. Curr Opin Gastroenterol. 2011;27:444.CrossRef Sah RP, Saluja A. Molecular mechanisms of pancreatic injury. Curr Opin Gastroenterol. 2011;27:444.CrossRef
21.
Zurück zum Zitat Grossman A, Boctor AM, Band P, Lane B. Role of steroids in secretion—modulating effect of triamcinolone and estradiol on protein synthesis and secretion from the rat exocrine pancreas. J Steroid Biochem. 1983;19:1069–1081.CrossRef Grossman A, Boctor AM, Band P, Lane B. Role of steroids in secretion—modulating effect of triamcinolone and estradiol on protein synthesis and secretion from the rat exocrine pancreas. J Steroid Biochem. 1983;19:1069–1081.CrossRef
22.
Zurück zum Zitat Xiang J, Liu X, Ren J, Chen K, Wang H-L, Miao Y-Y et al. How does estrogen work on autophagy? Autophagy. 2019;15:197–211.CrossRef Xiang J, Liu X, Ren J, Chen K, Wang H-L, Miao Y-Y et al. How does estrogen work on autophagy? Autophagy. 2019;15:197–211.CrossRef
23.
Zurück zum Zitat Yang Y-H, Chen K, Li B, Chen J-W, Zheng X-F, Wang Y-R et al. Estradiol inhibits osteoblast apoptosis via promotion of autophagy through the ER–ERK–mTOR pathway. Apoptosis. 2013;18:1363–1375.CrossRef Yang Y-H, Chen K, Li B, Chen J-W, Zheng X-F, Wang Y-R et al. Estradiol inhibits osteoblast apoptosis via promotion of autophagy through the ER–ERK–mTOR pathway. Apoptosis. 2013;18:1363–1375.CrossRef
24.
Zurück zum Zitat Yang Y, Zheng X, Li B, Jiang S, Jiang L. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss. Biochem Biophys Res Commun. 2014;451:86–92.CrossRef Yang Y, Zheng X, Li B, Jiang S, Jiang L. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss. Biochem Biophys Res Commun. 2014;451:86–92.CrossRef
25.
Zurück zum Zitat Choi S, Shin H, Song H, Lim HJ. Suppression of autophagic activation in the mouse uterus by estrogen and progesterone. J Endocrinol. 2014;221:39–50.CrossRef Choi S, Shin H, Song H, Lim HJ. Suppression of autophagic activation in the mouse uterus by estrogen and progesterone. J Endocrinol. 2014;221:39–50.CrossRef
26.
Zurück zum Zitat Wise PM, Ratner A. Effect of ovariectomy on plasma LH, FSH, estradiol, and progesterone and medial basal hypothalamic LHRH concentrations in old and young rats. Neuroendocrinology. 1980;30:15–19.CrossRef Wise PM, Ratner A. Effect of ovariectomy on plasma LH, FSH, estradiol, and progesterone and medial basal hypothalamic LHRH concentrations in old and young rats. Neuroendocrinology. 1980;30:15–19.CrossRef
27.
Zurück zum Zitat Blenck CL, Harvey PA, Reckelhoff JF, Leinwand LA. The Importance of biological sex and estrogen in rodent models of cardiovascular health and disease. Circ Res. 2016;118:1294–1312.CrossRef Blenck CL, Harvey PA, Reckelhoff JF, Leinwand LA. The Importance of biological sex and estrogen in rodent models of cardiovascular health and disease. Circ Res. 2016;118:1294–1312.CrossRef
Metadaten
Titel
Ovariectomy Affects Acute Pancreatitis in Mice
verfasst von
Melinda Wang
Fred Gorelick
Publikationsdatum
24.06.2021
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 7/2022
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-07116-w

Weitere Artikel der Ausgabe 7/2022

Digestive Diseases and Sciences 7/2022 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.