Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 25;68(3):451-459.
doi: 10.2478/jvetres-2024-0039. eCollection 2024 Sep.

Effect of central administration of indomethacin on anandamide-induced GnRH/LH secretion in the hypothalamus of anoestrous ewes

Dorota Tomaszewska-Zaremba  1 , Monika Tomczyk  2 , Karolina Wojtulewicz  2 , Joanna Bochenek  2 , Kinga Pałatyńska  1 , Andrzej Przemysław Herman  2
Affiliations

Effect of central administration of indomethacin on anandamide-induced GnRH/LH secretion in the hypothalamus of anoestrous ewes

Dorota Tomaszewska-Zaremba et al. J Vet Res. .

Abstract

Introduction: It is suggested that cannabinoids (CBs) may disturb reproduction through action on hypothalamic gonadotropin-releasing hormone (GnRH) neurons directly or indirectly through intermediates such as prostaglandins. The study aimed to determine the influence of intracerebroventricular (i.c.v.) injection of the endogenous cannabinoid anandamide (N-arachidonoylethanolamine - AEA), alone or with the prostaglandin synthesis inhibitor indomethacin (IND), on GnRH/luteinising hormone (LH) secretion. The purpose of the research was to clarify the role of endocannabinoids and their interaction with prostaglandins in the regulation of reproduction at the level of the hypothalamus and pituitary in anoestrous sheep.

Material and methods: The study was performed on 24 anoestrous ewes divided into four experimental groups: a control group receiving i.c.v. injection of Ringer-Locke solution, an AEA group that received i.c.v. injection of 30 μM of AEA, an IND group receiving i.c.v. injection of 5 μM of IND and an AEA + IND group that received i.c.v. injections of 30 μM of AEA and 5 μM of IND.

Results: Anandamide stimulated GnRH protein and gene expression in the median eminence and protein expression in the preoptic area without influencing GnRH messenger RNA (mRNA) in this structure. Indomethacin reversed the changes in GnRH secretion after AEA administration. It was also found that AEA stimulated LH mRNA in the pituitary without influencing LH release.

Conclusion: Our results support the role of endogenous cannabinoids in the regulation of reproductive processes at the central nervous system level. They may act directly on the hypothalamic GnRH neurons or indirectly through intermediates such as prostaglandins.

Keywords: anandamide; gonadotropin-releasing hormone; indomethacin; luteinising hormone.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article.

Figures

Fig. 1.
Fig. 1.
Effect of intracerebroventricular injection of anandamide (AEA) indomethacin (IND) and AEA + IND on the expression of the gonadotropin-releasing hormone (GnRH) gene in the preoptic area (POA – A) and median eminence (ME – B) of anoestrous ewes. Data are presented as the mean ± standard error of the mean. The results were analysed using two-way analysis of variance with a post-hoc Fisher’s least significance test (P-value ≤ 0.05)
Fig. 2.
Fig. 2.
Effect of intracerebroventricular injection of anandamide (AEA) indomethacin (IND) and AEA + IND on the gene expression of gonadotropin-releasing hormone receptor (GnRHR) in the median eminence (ME – A) and in the anterior pituitary (AP – B) of anoestrous ewes. The data are presented as the mean ± standard error of the mean. The results were analysed using two-way analysis of variance with a post-hoc Fisher’s least significance test (P-value ≤ 0.05)
Fig. 3.
Fig. 3.
Effect of intracerebroventricular injection of anandamide (AEA) indomethacin (IND) and AEA + IND on the content of gonadotropin-releasing hormone (GnRH) in the preoptic area (POA – A) and median eminence (ME – B) of anoestrous ewes. The data are presented as the mean ± standard error of the mean. The results were analysed using two-way analysis of variance with a post-hoc Fisher’s least significance test (P-value ≤ 0.01)
Fig. 4.
Fig. 4.
Effect of intracerebroventricular injection of anandamide (AEA), indomethacin (IND) and AEA + IND on the plasma concentration of luteinising hormone (LH –A) and on the expression of the LHβ gene (B) in the anterior pituitary (AP) of anoestrous ewes. The data are presented as the mean ± standard error of the mean. The results were analysed using two-way analysis of variance with a post-hoc Fisher’s least significance test (P-value ≤ 0.05)
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Aydin C., Yalcin M. Peripheral mechanisms involved in the pressor and bradycardic effects of centrally administered arachidonic acid Prostag Leukotr Ess Fatty Acids. 2008;78:361. doi: 10.1016/j.plefa.2008.04.007. : . , , –. , doi: . - DOI - PubMed
    1. Battista N., Meccariello R., Cobellis G., Fasano S., Di Tommaso M., Pirazzi V., Konje J.C., Pierantoni R., Maccarrone M. The role of endocannabinoids in gonadal function and fertility along the evolutionary axis Mol Cell Endocrinol. 2012;355:1. doi: 10.1016/j.mce.2012.01.014. : . , , –. , doi: . - DOI - PubMed
    1. Bigdeli H., Snyder P.J. Gonadotropin-releasing hormone release from the rat hypothalamus: dependence on membrane depolarization and calcium influx Endocrinology. 1978;103:281. doi: 10.1210/endo-103-1-281. : . , , –. , doi: . - DOI - PubMed
    1. Bosetti F. Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models J Neurochem. 2007;102:577. doi: 10.1111/j.1471-4159.2007.04558.x.. : . , , –. , doi: - DOI - PMC - PubMed
    1. Bradford M.M. A rapid and sensitive method for the quantitation of the microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem. 1976;72:248. doi: 10.1006/abio.1976.9999. : . , , –. , doi: . - DOI - PubMed

LinkOut - more resources