Activins, members of the TGFß family of
proteins, are widely expressed in a variety of tissues.
First identified based on their ability to regulate
biosynthesis and secretion of follicle-stimulating
hormone (FSH), activins have also been shown to
modulate development, cell growth, apoptosis, and
inflammation. Despite their many known functions, the
precise mechanisms and downstream signaling pathways
by which activins mediate their diverse effects remain
unknown. We have used a DNA microarray assay to
identify genes that are regulated by activin, alone or in
combination with gonadotropin-releasing hormone
(GnRH), another major regulator of FSH, in a murine
gonadotrope-derived cell line (LßT2). We used mRNA
from these cells to screen Affymetrix Mu74av2 mouse
Gene Chip oligonucleotide microarrays, representing
approximately 12,400 mouse genes. Treatment of LßT2
cells with activin A, a gonadotropin-releasing hormone
agonist (GnRHA) or activin A plus GnRHA resulted in
alterations in levels of gene expression that ranged in
magnitude from 15 to 67-fold. Data analysis identified
268 transcripts that were up- or down-regulated by twofold
or more. Distinct sets of genes were affected by
treatment with activin, GnRHA and activin plus
GnRHA, suggesting interactions between activin and
GnRHA. Changes in expression of seven randomly
selected representative genes identified by the
microarray technique were confirmed by real-time
quantitative PCR and semi-quantitative reverse
transcription/PCR (RT/PCR). Modulation of expression
of genes by activin suggests that activin may mediate its
effects through a variety of signaling pathways