Insulin-like growth factor II activates phosphatidylinositol 3-kinase-protooncogenic protein kinase 1 and mitogen-activated protein kinase cell signaling pathways, and stimulates migration of ovine trophectoderm cells

Jinyoung Kim, Gwonhwa Song, Haijun Gao, Jennifer L. Farmer, M. Carey Satterfield, Robert C. Burghardt, Guoyao Wu, Greg A. Johnson, Thomas E. Spencer, Fuller W. Bazer

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

IGF-II, a potent stimulator of cellular proliferation, differentiation, and development, regulates uterine function and conceptus growth in several species. In situ hybridization analyses found that IGF-II mRNA was most abundant in the caruncular endometrial stroma of both cyclical and pregnant ewes. In the intercaruncular endometrium, IGF-II mRNA transitioned from stroma to luminal epithelium between d 14 and 20 of pregnancy. IGF-II mRNA was present in all cells of the conceptus but was particularly abundant in the yolk sac. Immunohistochemical analyses revealed that phosphorylated (p)-protooncogenic protein kinase 1, p-ribosomal protein S6 kinase, p-ERK1/2, and p-P38 MAPK proteins were present at low levels in a majority of endometrial cells but were most abundant in the nuclei of endometrial luminal epithelium and conceptus trophectoderm of pregnant ewes. In mononuclear trophectoderm cells isolated from d-15 conceptuses, IGF-II increased the abundance of p-pyruvate dehydrogenase kinase 1, p-protooncogenic protein kinase 1, p-glycogen synthase kinase 3B, p-FK506 binding protein 12-rapamycin associated protein 1, and p-ribosomal protein S6 kinase protein within 15 min, and the increase was maintained for 90 min. IGF-II also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was maximal at 15 or 30 min posttreatment. Moreover, IGF-II increased migration of trophectoderm cells. Collectively, these results support the hypothesis that IGF-II coordinately activates multiple cell signaling pathways critical to survival, growth, and differentiation of the ovine conceptus during early pregnancy.

Original languageEnglish
Pages (from-to)3085-3094
Number of pages10
JournalEndocrinology
Volume149
Issue number6
DOIs
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Insulin-Like Growth Factor II
Mitogen-Activated Protein Kinases
Protein Kinases
Sheep
Ribosomal Protein S6 Kinases
p38 Mitogen-Activated Protein Kinases
Messenger RNA
Epithelium
TOR Serine-Threonine Kinases
Glycogen Synthase Kinases
Pregnancy
Yolk Sac
Proteins
Critical Pathways
Growth
Endometrium
Cell Movement
In Situ Hybridization
Cell Proliferation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin-like growth factor II activates phosphatidylinositol 3-kinase-protooncogenic protein kinase 1 and mitogen-activated protein kinase cell signaling pathways, and stimulates migration of ovine trophectoderm cells. / Kim, Jinyoung; Song, Gwonhwa; Gao, Haijun; Farmer, Jennifer L.; Satterfield, M. Carey; Burghardt, Robert C.; Wu, Guoyao; Johnson, Greg A.; Spencer, Thomas E.; Bazer, Fuller W.

In: Endocrinology, Vol. 149, No. 6, 01.06.2008, p. 3085-3094.

Research output: Contribution to journalArticle

Kim, Jinyoung ; Song, Gwonhwa ; Gao, Haijun ; Farmer, Jennifer L. ; Satterfield, M. Carey ; Burghardt, Robert C. ; Wu, Guoyao ; Johnson, Greg A. ; Spencer, Thomas E. ; Bazer, Fuller W. / Insulin-like growth factor II activates phosphatidylinositol 3-kinase-protooncogenic protein kinase 1 and mitogen-activated protein kinase cell signaling pathways, and stimulates migration of ovine trophectoderm cells. In: Endocrinology. 2008 ; Vol. 149, No. 6. pp. 3085-3094.
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AU - Farmer, Jennifer L.

AU - Satterfield, M. Carey

AU - Burghardt, Robert C.

AU - Wu, Guoyao

AU - Johnson, Greg A.

AU - Spencer, Thomas E.

AU - Bazer, Fuller W.

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