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Simple Summary  GnRH and FSH play an important regulatory role in the reproductive activities of mammals. At present, many artificially synthesized GnRH analogues have been used in the regulation of cattle reproduction and the clinical treatment of various reproductive diseases. This study explored the potential mechanism of miR-488 in GnRH regulation of FSH synthesis and secretion and provides a theoretical basis for the application of GnRH analogue in cattle artificial breeding. We hope to provide a research foundation for improving the processing procedures of cattle estrus control and the domestic application of hormone products.    Abstract  Gonadotropin-releasing hormone (GnRH), which is synthesized and released by the hypothalamus, promotes the synthesis and secretion of follicle-stimulating hormone (FSH), thereby regulating the growth and reproduction of animals. GnRH analogues have been widely used in livestock production. MiRNAs, which are endogenous non-coding RNAs, have been found to play important roles in hormone regulation and other physiological processes in recent years. However, the roles of miRNAs in GnRH-mediated regulation of FSH secretion have rarely been studied. Herein, we treated bovine anterior adenohypophyseal cells with an exogenous GnRH analogue and found that miR-488 was differentially expressed. Through a combination of TargetScan prediction and dual luciferase reporter analysis, miR-488 was confirmed to be able to target the FSHB gene. Based on this finding, we verified the expression of Fshβ and Lhβ mRNA in the rat adenohypophysis before and after exogenous GnRH treatment in vivo and in vitro. Experiments on rat anterior adenohypophyseal cells showed that overexpression of miR-488 significantly inhibited Fshβ expression and FSH synthesis, while knockdown of miR-488 had the opposite effects. Our results demonstrate that GnRH relies on miR-488 to regulate FSH synthesis, providing additional useful evidence for the significance of miRNAs in the regulation of animal reproduction.

Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells