| First Author | Kapfhamer J | Year | 2018 |
| Journal | Mol Cell Endocrinol | Volume | 470 |
| Pages | 179-187 | PubMed ID | 29107092 |
| Mgi Jnum | J:263342 | Mgi Id | MGI:6163899 |
| Doi | 10.1016/j.mce.2017.10.012 | Citation | Kapfhamer J, et al. (2018) The Galphaq/11-provoked induction of Akr1c18 in murine luteal cells is mediated by phospholipase C. Mol Cell Endocrinol 470:179-187 |
| abstractText | Towards the end of gestation prostaglandin F2alpha (PGF2alpha) stimulates the expression of Akr1c18 in the murine corpus luteum. Akr1c18 codes for 20alpha-hydroxysteroid dehydrogenase, an enzyme that precipitates parturition by catabolizing progesterone. Previous results from our laboratory have shown that this effect of PGF2alpha is mediated by the activation of Galphaq/11, but the downstream effector(s) of Galphaq/11 that elicit the increase in Akr1c18 expression have not been identified. The physiological effects of Galphaq/11 are mediated by its ability to interact with phospholipase Cbeta, p63RhoGEF, and PKCzeta. In the experiments described herein we used biochemical and pharmacological approaches, as well as adenoviral-mediated expression of a constitutively active form of Galphaq and mutants thereof, to examine the role of each of these effectors as potential mediators of the increased expression of luteal Akr1c18. By measuring the effects of PGF2alpha on the activation of RhoA (activated by p63RhoGEF) and the effects of activators and inhibitors of RhoA on the PGF2alpha-induced expression of luteal Akr1c18, we determined that RhoA is neither activated by PGF2alpha or involved in the PGF2alpha-induced expression of luteal Akr1c18. The potential involvement of PKCzeta was ruled out by the inability of a mutant of a constitutively active Galphaq that prevents PKCzeta binding to block the increased expression of Akr1c18. Furthermore, PGF2alpha does not increase the phosphorylation of ERK-5, the only known downstream target of PKCzeta. On the other hand, three different mutants of a constitutively active Galphaq that prevent phospholipase C activation blocked the induction of luteal Akr1c18. We conclude that the induction of luteal Akr1c18 by Galphaq/11 is mediated by the activation of phospholipase C. |
