Abstract
Simple SummaryThis review aims to discuss the role of the guanosine nucleotide-binding protein (RAS) family in the biological events that occur during the formation and regression of the corpus luteum in the ovary. RAS proteins mediate extracellular signals, transduce through their receptors via multiple signaling pathways, and regulate a wide array of cellular processes. RAS exhibits a notable function in the regulation of vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor, angiopoietins (ANPT), and hypoxia-inducible factor (HIF). RAS proteins appear to be involved in several factors that are notably associated with the regulation of the corpus luteum. Further research is necessary to enhance our understanding of the role of the RAS family in the ovarian corpus luteum.The corpus luteum is a temporary endocrine gland in the ovary. In the ovarian cycle, repeated patterns of specific cellular proliferation, differentiation, and transformation occur that accompany the formation and regression of the corpus luteum. Molecular mechanism events in the ovarian microenvironment, such as angiogenesis and apoptosis, are complex. Recently, we focused on the role of RAS protein in the ovarian corpus luteum. RAS protein plays a vital role in the modulation of cell survival, proliferation, and differentiation by molecular pathway signaling. Additionally, reproductive hormones regulate RAS activity in the cellular physiological function of ovarian follicles during pre-ovulatory maturation and ovulation. Thus, we have reviewed the role of RAS protein related to the biological events of the corpus luteum in the ovary.
Highlights
The ovary is a dynamic female reproductive organ that undergoes many structural and functional transformations as it fulfills its two significant roles of producing female gametes and synthesizing sex steroid hormones [1]
RAS family proteins include 23 genes coding for at least 25 proteins that are divided into eight paralog groups based on sequence identity, structure, and function: RAS, RASlike (RAL), RAS-related protein (R-RAS), RAS-like protein in tissues (RIT), RAS-related protein Rap (RAP), RAS homolog enriched in brain (RHEB), Dexamethasone-induced RASrelated protein (RASD), and guanosine triphosphate (GTP)-binding protein Di-RAS (DIRAS) [5]
Another vasoactive substance like insulin-like growth factor (IGF) exhibited similar expression patterns and appeared to have an identical role to fibroblast growth factor (FGF) during the corpus luteum regression, in which the IGF was upregulated during the functional luteolysis; when the structural luteolysis began, IGF expression was significantly reduced, which indicated the termination of supporting the functional corpus luteum [76]
Summary
The ovary is a dynamic female reproductive organ that undergoes many structural and functional transformations as it fulfills its two significant roles of producing female gametes and synthesizing sex steroid hormones [1]. In the ovarian cycle, repeated patterns of specific cellular proliferation, differentiation, and transformation occur that accompany the process of follicular development and the formation and function of the corpus luteum [2]. The monomeric small GTPases (small G proteins) are known to play an important role in diverse molecular processes. RAS family proteins play a vital role in the modulation of cell survival, proliferation, and differentiation by signaling through a set of molecular pathways [10]. Those molecular functions of RAS family proteins exhibit an essential role that co-occurs in the repeated pattern of physiological change during the ovarian cycle. This review aims to discuss the role of RAS family proteins related to biological events in the ovarian corpus luteum
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