Differential regulation of kit ligand A (kitlga) expression in the zebrafish ovarian follicle cells – Evidence for the existence of a cyclic adenosine 3′, 5′ monophosphate-mediated binary regulatory system during folliculogenesis

• Published in: Molecular and cellular endocrinology Vol. 402; pp. 21 - 31
• Main Authors: Yao, Kai, Ge, Wei
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15.02.2015
• Subjects: Adenosines; adenylate cyclase; Animals; cAMP; cAMP-dependent protein kinase; Cells, Cultured; cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Danio rerio; developmental stages; Epac; Female; follicle-stimulating hormone; follicular development; forskolin; Freshwater; Gene Expression; Gene Expression Regulation, Developmental; germinal vesicle; granulosa cells; Guanine Nucleotide Exchange Factors - metabolism; Hormones; human chorionic gonadotropin; Inhibitors; insulin-like growth factor I; Kinases; Kit ligand A; Ligands; luteinizing hormone; Luteinizing Hormone - physiology; mammals; meiosis; Oogenesis; Ovarian Follicle - growth & development; Ovarian Follicle - metabolism; Ovary; Pathways; phosphorylation; PKA; polypeptides; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Second Messenger Systems; stem cell factor; Stem Cell Factor - genetics; Stem Cell Factor - metabolism; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Kit ligand A; Ovary; Zebrafish; cAMP; Epac; PKA
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2014.12.005

•Kit ligand A (Kitlga) is expressed in the follicle cells in the zebrafish ovary.•The expression of Kitlga is subject to regulation by gonadotropins.•cAMP is involved in controlling Kitlga expression in vitro.•The cAMP-PKA pathway stimulates Kitlga expression whereas cAMP-Epac suppresses it.•The two pathways may change their signaling intensity during folliculogenesis. Kit ligand (Kitl) is an important paracrine factor involved in the activation of primordial follicles from the quiescent pool and in the maintenance of meiotic arrest before germinal vesicle breakdown (GVBD). It has been reported that follicle-stimulating hormone (FSH) stimulates but luteinizing hormone (LH) suppresses the expression of Kitl in the granulosa cells in mammals. Considering that both gonadotropins signal in the follicle cells mainly by activating cyclic adenosine 3′, 5′-monophosphate (cAMP) pathway, we are intrigued by how cAMP differentially regulates Kitl expression. In the present study, we demonstrated that both human chorionic gonadotropin (hCG) and pituitary adenylate cyclase activating polypeptide (PACAP) inhibited insulin-like growth factor I (IGF-I)-induced Akt phosphorylation and kitlga expression in the zebrafish follicle cells. Further experiments showed that cAMP was involved in regulating the expression of kitlga. However, two cAMP-activated effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), had converse effects. PKA promoted whereas Epac inhibited the expression of kitlga, as demonstrated by the respective activators. Interestingly, cAMP also appeared to exert differential effects on kitlga expression at different stages of follicle development during folliculogenesis, significantly stimulating kitlga expression at the early growth stage but suppressing it at the full-grown stage before final oocyte maturation, implying a potential mechanism for differential effects of the same pathway at different stages. The inhibitory effect of forskolin (activator of adenylate cyclase) and H89 (inhibitor of PKA) on IGF-I-induced expression of kitlga suggested cross-talk between the cAMP and IGF-I-activated PI3K-Akt pathways. This study, together with our previous findings on IGF-I regulation of kitlga expression, provides important clues to the underlying mechanism that regulates Kit ligand expression during folliculogenesis in the ovary.