A proteomic study reveals new markers of prolactin-modulated ovarian function in plains vizcachas

Abstract

Prolactin (PRL) modulates the expression of the LH receptor in the ovary and, thus, the cascades of steroidogenic enzymes that synthesize and produce ovarian steroids. When pathological hyperprolactinemia occurs, the pulsatile release of GnRH decreases and alters the pituitary production of FSH and LH. Furthermore, it directly impairs the endocrine activity of ovarian follicles. To analyze which ovarian factors, aside to the aforementioned enzymes, respond to a high PRL environment, an ovarian proteomic study of vizcachas with sulpiride-induced hyperprolactinemia was performed. For this, ovarian protein extracts from hyperprolactinemic (HPRL) and control (CTL) females (n=5 per group) were used. Briefly, equal amounts of protein were analyzed using MALDI-TOF/MS and then, LC-ESI/ MS (Orbitrap). The resulting peptides were identified with Proteome Discoverer Software using the Rodentia UniProt Database, and functional enrichment analysis was performed using DAVID, STRING and FunRich softwares. Proteins differentially expressed in each treatment were depicted in a volcano plot (t-test, p <0.05). Functional enrichment analysis showed that 24 proteins were differentially expressed in HPRL ovarian tissue compared to that of CTLs. Among those, some cytoskeleton regulation markers such as annexin 2 (ANXA2), Actin related protein 2/3 complex subunit 5 like (Arpc5l), and Myosin regulatory light chain 12A (MYLC12A) prevailed in HPRL-ovaries, while other markers related to mitochondrial function as Dynamin-1-like protein (DNM1L), SuccinateCoA ligase (SUCLG2), and Mitochondrial fission 1 protein (FIS1) were down-regulated. In addition, the interactomes showed different network topology with different nodal peptides in HPRL vs CTL treatments. The present work showed an ovarian expression profile that significantly varies under a hyperprolactinemic environment. Finally, this report provides new markers for future investigations on PRL-dependent modulation of ovarian function.