TY - JOUR
T1 - Insulin augments GnRH-stimulated LHβ gene expression by Egr-1
AU - Buggs, Colleen
AU - Weinberg, Frank
AU - Kim, Ellen
AU - Wolfe, Andrew
AU - Radovick, Sally
AU - Wondisford, Fredric
N1 - Funding Information:
We thank P. Mellon for generously providing LβT2 cells to perform these studies. We thank J. Harris, R. Lurvey, and A.T. Mpungu for excellent technical assistance. This work was supported by grants from the National Institutes of Health (NICHD U54 HD41859 and P60 DK20595) to S.R. and F.E.W. as well as grants from the National Institutes of Health (NIDDK DK069518-01) and the Robert Wood Johnson Foundation to C.B.
PY - 2006/4/25
Y1 - 2006/4/25
N2 - Previous studies have shown that insulin augments GnRH-stimulated LH synthesis and release from primary gonadotrophs. In this study, regulation of LHβ gene expression by GnRH and insulin was examined in LβT2 cells. Endogenous LHβ mRNA is stimulated 2.4-fold by insulin alone, 2.6-fold by GnRH alone, and 4.7-fold by insulin together with GnRH. This effect of insulin, like GnRH, mapped to sequences -140 to +1 in the mouse LHβ gene. Insulin together with GnRH stimulates activity of an LHβ-reporter gene 7.1-fold; whereas, GnRH alone or insulin alone stimulates the reporter activity 2.8- and 3.1-fold, respectively. Blocking the binding of Egr-1 to sequences -51 to -42 in the LHβ gene inhibits effects of insulin and GnRH. Insulin together with GnRH increases Egr-1 mRNA levels and total Egr-1 binding to LHβ DNA. These findings indicate that insulin may impact regulation of the reproductive axis at the level of the pituitary.
AB - Previous studies have shown that insulin augments GnRH-stimulated LH synthesis and release from primary gonadotrophs. In this study, regulation of LHβ gene expression by GnRH and insulin was examined in LβT2 cells. Endogenous LHβ mRNA is stimulated 2.4-fold by insulin alone, 2.6-fold by GnRH alone, and 4.7-fold by insulin together with GnRH. This effect of insulin, like GnRH, mapped to sequences -140 to +1 in the mouse LHβ gene. Insulin together with GnRH stimulates activity of an LHβ-reporter gene 7.1-fold; whereas, GnRH alone or insulin alone stimulates the reporter activity 2.8- and 3.1-fold, respectively. Blocking the binding of Egr-1 to sequences -51 to -42 in the LHβ gene inhibits effects of insulin and GnRH. Insulin together with GnRH increases Egr-1 mRNA levels and total Egr-1 binding to LHβ DNA. These findings indicate that insulin may impact regulation of the reproductive axis at the level of the pituitary.
KW - Egr-1
KW - GnRH
KW - Insulin
KW - Luteinizing hormone
UR - http://www.scopus.com/inward/record.url?scp=33645883547&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2006.02.001
DO - 10.1016/j.mce.2006.02.001
M3 - Article
C2 - 16530935
AN - SCOPUS:33645883547
SN - 0303-7207
VL - 249
SP - 99
EP - 106
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -