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Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility.
Mol Hum Reprod 2005; 11(1):21-8MH

Abstract

The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are under the negative control of leptin in the rodent hypothalamus. As leptin and endocannabinoids play opposite roles in the control of reproduction, we have investigated whether the impaired fertility typical of leptin-defective ob/ob mice is due, in part, to enhanced uterine endocannabinoid levels. We found that levels of both anandamide and 2-AG in the uterus of ob/ob mice are significantly elevated with respect to wild-type littermates, due to reduced hydrolase activity in the case of anandamide, and to reduced monoacylglycerol lipase and enhanced diacylglycerol lipase activity in the case of 2-AG. Furthermore, the process mediating endocannabinoid cellular uptake was also impaired in ob/ob mice, whereas the levels of cannabinoid and anandamide receptors were not modified. Although ineffective in wild-type mice, treatment of ob/ob mice with leptin re-established endocannabinoid levels and enzyme activities back to the values observed in wild-type littermates. Finally, treatment of ob/ob females with the CB1 receptor antagonist SR141716A did not improve their fertility, and inhibition of endocannabinoid inactivation with the endocannabinoid uptake inhibitor OMDM-1 in wild-type females did not result in impaired fertility.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy. Maccarrone@vet.unite.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15563449

Citation

Maccarrone, M, et al. "Up-regulation of the Endocannabinoid System in the Uterus of Leptin Knockout (ob/ob) Mice and Implications for Fertility." Molecular Human Reproduction, vol. 11, no. 1, 2005, pp. 21-8.
Maccarrone M, Fride E, Bisogno T, et al. Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility. Mol Hum Reprod. 2005;11(1):21-8.
Maccarrone, M., Fride, E., Bisogno, T., Bari, M., Cascio, M. G., Battista, N., ... Di Marzo, V. (2005). Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility. Molecular Human Reproduction, 11(1), pp. 21-8.
Maccarrone M, et al. Up-regulation of the Endocannabinoid System in the Uterus of Leptin Knockout (ob/ob) Mice and Implications for Fertility. Mol Hum Reprod. 2005;11(1):21-8. PubMed PMID: 15563449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility. AU - Maccarrone,M, AU - Fride,E, AU - Bisogno,T, AU - Bari,M, AU - Cascio,M G, AU - Battista,N, AU - Finazzi Agrò,A, AU - Suris,R, AU - Mechoulam,R, AU - Di Marzo,V, Y1 - 2004/11/23/ PY - 2004/11/26/pubmed PY - 2005/9/2/medline PY - 2004/11/26/entrez SP - 21 EP - 8 JF - Molecular human reproduction JO - Mol. Hum. Reprod. VL - 11 IS - 1 N2 - The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are under the negative control of leptin in the rodent hypothalamus. As leptin and endocannabinoids play opposite roles in the control of reproduction, we have investigated whether the impaired fertility typical of leptin-defective ob/ob mice is due, in part, to enhanced uterine endocannabinoid levels. We found that levels of both anandamide and 2-AG in the uterus of ob/ob mice are significantly elevated with respect to wild-type littermates, due to reduced hydrolase activity in the case of anandamide, and to reduced monoacylglycerol lipase and enhanced diacylglycerol lipase activity in the case of 2-AG. Furthermore, the process mediating endocannabinoid cellular uptake was also impaired in ob/ob mice, whereas the levels of cannabinoid and anandamide receptors were not modified. Although ineffective in wild-type mice, treatment of ob/ob mice with leptin re-established endocannabinoid levels and enzyme activities back to the values observed in wild-type littermates. Finally, treatment of ob/ob females with the CB1 receptor antagonist SR141716A did not improve their fertility, and inhibition of endocannabinoid inactivation with the endocannabinoid uptake inhibitor OMDM-1 in wild-type females did not result in impaired fertility. SN - 1360-9947 UR - https://www.unboundmedicine.com/medline/citation/15563449/Up_regulation_of_the_endocannabinoid_system_in_the_uterus_of_leptin_knockout__ob/ob__mice_and_implications_for_fertility_ L2 - https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gah130 DB - PRIME DP - Unbound Medicine ER -