Microarray Analysis of the in Vivo Effects of Hypophysectomy and Growth Hormone Treatment on Gene Expression in the Rat*

Abstract

Complementary DNA microarrays containing 3000 different rat genes were used to study the consequences of severe hormonal deficiency (hypophysectomy) on the gene expression patterns in heart, liver, and kidney. Hybridization signals were seen from a majority of the arrayed complementary DNAs; nonetheless, tissue-specific expression patterns could be delineated. Hypophysectomy affected the expression of genes involved in a variety of cellular functions. Between 16-29% of the detected transcripts from each tissue changed expression level as a reaction to this condition. Chronic treatment of hypophysectomized animals with human GH also caused significant changes in gene expression patterns. The study confirms previous knowledge concerning certain gene expression changes in the above-mentioned situations and provides new information regarding hypophysectomy and chronic human GH effects in the rat. Furthermore, we have identified several new genes that respond to GH treatment. Our results represent a first step toward a more global understanding of gene expression changes in states of hormonal deficiency.

Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver

“…A recent study employing promoter microarrays identified that 12%, 1·7%, and 1·6% of 13 000 gene promoters were bound by HNF-4 , HNF-1 , and HNF-6 in hepatocytes respectively (Odom et al 2004). Thus, the number of genes whose expression in the liver is regulated by GH might be much larger than has been indicated by gene expression studies using cDNA or oligonucleotide microarrays (Thompson et al 2000, Flores-Morales et al 2001, Olsson et al 2003, Ahluwalia et al 2004.…”

“…A cross examination of the list of genes that have been shown to be regulated by GH (Thompson et al 2000, Flores-Morales et al 2001, Olsson et al 2003, Ahluwalia et al 2004 and the list of genes that have been identified to contain binding sites for HNF-3 , HNF-3 , HNF-6, HNF-4 , C/EBP , or DBP (Schrem et al 2002, Odom et al 2004) could identify a number of candidate genes whose expression in the liver may be regulated by GH through these LETFs. For example, the expression of CYP3A4 (Liddle et al 1998, Jaffe et al 2002, tyrosine-aminotransferase (TAT) (Ahluwalia et al 2004), and transferrin (Tf) (Flores-Morales et al 2001) in the liver were shown to be stimulated by continuous GH administration. The expression of CYP3A4 (RodriguezAntona et al 2003), and TAT and Tf (Kaestner et al 1998) in the liver has also been shown to depend on HNF-3 .…”

“…A gene expression analysis with a cDNA array containing 588 rat cDNAs identified eight novel transcripts from the rat liver that were regulated by GH (Thompson et al 2000). Using a cDNA microarray representing 3000 rat sequences, Flores-Morales et al (2001) found that 58 of 720 detectable mRNAs were regulated by GH in the rat liver, many of which were not previously known to be GH responsive. Using a microarray containing 11 000 rat expression sequence tags (ESTs), Olsson et al (2003) identified 58 metabolic genes (i.e.…”

“…Using a microarray consisting of 5889 unique rat genes, Ahluwalia et al (2004) identified 27 female-and 44 male-predominant genes that were regulated by GH in the rat liver. These GH-regulated genes are involved in metabolism, detoxification, growth control and other functions of the liver (Thompson et al 2000, Flores-Morales et al 2001, Olsson et al 2003, Ahluwalia et al 2004. Thus, regulation of gene expression appears to be a major mechanism by which GH affects the function of the liver.…”

Microarrays as toxin sensors

“…It might be informative to look more globally at CCl 4 -induced changes using a more extensive rat microarray 15 or a whole-genome microarray containing B30 000 targets.…”