Leptin decreases the transcription of BKCa channels and Gs to Gi protein-ratio in late pregnant rat uterus

Obesity can have a significant impact on pregnancy outcomes by compromising the ability of the uterus to relax, which increases the likelihood of conditions such as preterm labor. One of the key pathways responsible for uterine relaxation is the beta-adrenergic signaling pathway, and it is well-documented that obesity, often linked to a high-fat diet, can disrupt this pathway within the uterine environment. Hyperleptinemia is a significant feature of pregnancy as well as obesity. However, the effect of leptin on beta-adrenergic signaling pathway has not been studied. In the present study, we studied the effects of leptin on transcriptions of the major proteins defining the beta-adrenergic signaling pathway in pregnant rat uterus. Leptin treatment at a supraphysiological concentration to pregnant rat uterine strips increased the mRNA and protein expressions of Gs protein but not the mRNA of beta 2- and beta 3-adrenoceptors. It also enhanced the expression of Gi-protein, but not the Gq protein. Nevertheless, the mRNA ratio of Gs to Gi protein experienced a significant decrease. Further, leptin reduced the transcription of BKCa alpha and BKCa beta channel subunits. In leptin-stimulated tissues, there was also an increase in the expression of leptin receptor and JAK-2. In conclusion, leptin decreases the ratio of Gs to Gi proteins and BKCa alpha and BKCa beta channel subunits suggesting hyperleptinemia is a likely factor inducing uterine relaxant dysfunction in obesity.