LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis.
The Lin-11, Isl-1, and Mec-3 (LIM) homeodomain transcription factor Isl-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Our recent studies have shown that Isl-1 is mainly located in the pituitary gonadotropes throughout pituitary development and persists to adulthood. We still do not know the physiological functions of Isl-1 expression and its related mechanisms in the pituitary gland. The aim of the present study was to examine the hypothesis that Isl-1 is involved in regulating pituitary gonadotropin hormone (FSH/LH) production by activating FSHβ and LHβ gene expressions. We have shown that Isl-1 activates FSHβ and LHβ subunit promoters and endogenous gene transcription in LβT2 cells. In addition, Isl-1 overexpression significantly increased FSH synthesis and secretion but not LH. The actions of Isl-1 were not observed when the homeodomain or LIM1 domains are mutated. This demonstrates that Isl-1 induction of FSHβ and LHβ is by both direct and indirect binding of Isl-1 to DNA sequences. Furthermore, Isl-1 expressional level was up-regulated in LβT2 cells after exposure to GnRH, activin, and leptin. However, RNA interference-induced knockdown of Isl-1 significantly reduced the effect of leptin but did not obviously influence the stimulating effects of GnRH and activin on LH and FSH production. In conclusion, the results demonstrate that the LIM-homeodomain transcription factor Isl-1 functions to increase FSHβ/LHβ gene transcription, and mediates the effects of leptin on gonadotropin synthesis.
Wu
Yingjie
Y
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, People's Republic of China.
Luo
Haoshu
H
Liu
Jiali
J
Kang
Duo
D
McNeilly
Alan S
AS
Cui
Sheng
S
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D052681:Gonadotrophs / Q000187:drug effects / Q000378:metabolism; D006062:Gonadotropins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D037201:Follicle Stimulating Hormone, beta Subunit; D006062:Gonadotropins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D020738:Leptin; D037101:Luteinizing Hormone, beta Subunit; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1