Effect of Central Injection of Anandamide on LPS-Dependent Suppression of GnRH/LH Secretion in Ewes During the Follicular Phase of the Estrous Cycle

The study investigated the effects of intracerebroventricular (ICV) administration of the endocannabinoid anandamide (AEA) on suppression of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) secretion during lipopolysaccharide (LPS)-induced inflammation in ewes at the follicular phase of the estrous cycle. Animals were divided into three groups: control, LPS (intravenous, IV; 400 ng/kg), and LPS + AEA (ICV; 100 µM/animal). In LPS-treated ewes, AEA increased GnRH concentration in the preoptic area (POA) and upregulated GnRH mRNA expression in the POA and anterior hypothalamus (AHA). Central administration of AEA decreased the circulating concentration of cortisol in LPS-treated ewes. Moreover, AEA lowered proinflammatory interleukin (IL)-1β and increased anti-inflammatory IL-10 protein expressions in the hypothalamus of LPS-treated ewes. However, ICV AEA did not reverse the inflammation-associated reduction in LH secretion. These findings show that acute central administration of AEA abolishes the inhibitory effect of inflammation on GnRH synthesis in the POA and even stimulates it, likely through attenuation of central inflammation, as reflected by IL-1β and IL-10 changes in the POA. Nevertheless, short-term AEA administration was insufficient to counteract the inflammation-mediated suppression of LH secretion. Further studies are needed to explore the role of endocannabinoids (ECBs) in modulating GnRH/LH secretion under inflammatory conditions, particularly with prolonged exposure.