A novel role of FSH on regulating ovarian adiponectin expression in rat ovarian granulosa cells

Abstract

Background: Adiponectin, also known as Acrp30, GBP28, or apM1, plays a crucial role in regulating glucose levels, lipid metabolism and insulin sensitivity in various tissues and organs. Despite its broad physiological relevance in female reproduction, its role in ovarian adiponectin secretion and energy utilization remains unknown. Methods: In the present investigation, we employed a suite of sophisticated molecular and cellular techniques to elucidate the expression of lipocalin system components and glucose transporter proteins within the ovarian tissue of rats. Specifically, cellular immunofluorescence, RT-PCR, Western blotting, and immunohistochemistry, alongside ELISA, were meticulously applied for the identification of these proteins. Furthermore, granulosa cells, harvested from rat ovaries, were subjected to an in vitro culture protocol to establish a primary cell culture. Results: In our study, we utilized primary cultured rat granulosa cells to demonstrate for the first time that FSH quickly stimulated adiponectin protein expression in granulosa cells, particularly through the PKA signaling pathway. Consistently, further in vivo study indicated that eCG administration significantly increased adiponectin protein levels in rat ovaries. The subsequent ovarian transcriptome and RT-PCR analysis showed a positive correlation between the expression of intraovarian glucose transporters (Slc2a1, Slc2a3, and Slc2a4) and the adiponectin system (Adipoq, Adipor1, and Adipor2), as well as the protein expression patterns. Although eCG administration in rats notably elevated circulating adiponectin levels, it had no significant effects on blood glucose levels. The current findings proved that AdipoRon (an AdipoR agonist) significantly increased the expression of glucose transporters (GLUT1 and GLUT2) proteins levels, enhancing glucose uptake in granulosa cells. Conclusions: These findings indicate that FSH may modulate ovarian glucose transporter protein expression and glucose utilization through the autocrine actions of adiponectin, thereby influencing ovarian development and function.