TY - JOUR
T1 - The ERK Signaling Cascade Inhibits Gonadotropin-Stimulated Steroidogenesis
AU - Seger, Rony
AU - Hanoch, Tamar
AU - Rosenberg, Revital
AU - Dantes, Ada
AU - Merz, Wolfgang E.
AU - Strauss, Jerome F.
AU - Amsterdam, Abraham
N1 - This work was supported by grants from the Benozyio Institute for Molecular Medicine at the Weizmann Institute of Science and from the Estate of Siegmund Landau to RS and the Israel Academy of Science to AA, and NIH grant HD-06224 to JFS. AA was an incumbent of the Joyce and Ben. B. Eisenberg professorial chair in molecular endocrinology and cancer research. RS is an incumbent of the Yale S. Lewine and Ella Miller Lewine professorial chair for cancer research.
PY - 2023/1/13
Y1 - 2023/1/13
N2 - The response of granulosa cells to Luteinizing Hormone (LH) and Follicle- Stimulating Hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) signaling. Notably, the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively. We found that stimulation of these cells with the appropriate gonadotropin induced ERK activation as well as progesterone production downstream of PKA. Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production, which was correlated with increased expression of the Steroidogenic Acute Regulatory Protein (StAR), a key regulator of progesterone synthesis. Therefore, it is likely that gonadotropin-stimulated progesterone formation is regulated by a pathway that includes PKA and StAR, and this process is down-regulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis but also activates down-regulation machinery involving the ERK cascade. The activation of ERK by gonadotropins as well as by other agents may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis.
AB - The response of granulosa cells to Luteinizing Hormone (LH) and Follicle- Stimulating Hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) signaling. Notably, the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively. We found that stimulation of these cells with the appropriate gonadotropin induced ERK activation as well as progesterone production downstream of PKA. Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production, which was correlated with increased expression of the Steroidogenic Acute Regulatory Protein (StAR), a key regulator of progesterone synthesis. Therefore, it is likely that gonadotropin-stimulated progesterone formation is regulated by a pathway that includes PKA and StAR, and this process is down-regulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis but also activates down-regulation machinery involving the ERK cascade. The activation of ERK by gonadotropins as well as by other agents may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis.
U2 - 10.26502/jbb.2642-91280066
DO - 10.26502/jbb.2642-91280066
M3 - مقالة
SN - 2642-9128
VL - 6
SP - 1
EP - 12
JO - Journal of Biotechnology and Biomedicine
JF - Journal of Biotechnology and Biomedicine
IS - 1
ER -