Temporal profile of estrogen-dependent gene expression in LHRH-producing GT1-7 cells.
The long-term cellular effects of estrogens are mediated by nuclear estrogen receptors which act as transcription factors to regulate gene expression. Hypothalamic targets of estrogen action include luteinizing hormone-releasing hormone-secreting neurons controlling reproduction in vertebrates. Microarray analysis and qRT-PCR studies were performed on GT1-7, immortalized LHRH neurons after 17beta-estradiol treatment to reveal the nature of estrogen-regulated genes and the time course of changes in their expression profile. More than 1000 transcripts showed robust responses to estrogen treatment and the majority of responding genes were up-regulated. Early-responding genes showed altered expression 0.5-2h after estrogen exposure, whereas late-responding genes changed after 24-48h treatment. Up-regulated genes encoded transcription factors, molecules involved in cellular movement, cell death, immune response, neurotransmitter and neuropeptide receptors, ion channels and transporters. The 17beta-estradiol modulation of 12 genes - representing characteristic gene clusters - has been confirmed by qRT-PCR. Our studies highlighted diverse gene networks, cell regulatory mechanisms and metabolic pathways through which estrogen may alter gene expression in immortalized LHRH neurons. The findings also support the notion that genomic effects of estrogen targeting in vivo directly the LHRH neuronal network of mammals play an important role in the central feedback regulation of the reproductive axis by estrogen.
Varju
Patricia
P
Institute of Experimental Medicine, Hungarian Academy of Sciences, Laboratory of Endocrine Neurobiology, Szigony u. 43, Budapest H-1083, Hungary.
Chang
Ken C
KC
Hrabovszky
Erik
E
Merchenthaler
István
I
Liposits
Zsolt
Z
D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D007473:Ion Channels; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol