Exploring hepatic hormone actions using a compilation of gene expression profiles.
BACKGROUND
Microarray analysis is attractive within the field of endocrine research because regulation of gene expression is a key mechanism whereby hormones exert their actions. Knowledge discovery and testing of hypothesis based on information-rich expression profiles promise to accelerate discovery of physiologically relevant hormonal mechanisms of action. However, most studies so-far concentrate on the analysis of actions of single hormones and few examples exist that attempt to use compilation of different hormone-regulated expression profiles to gain insight into how hormone act to regulate tissue physiology. This report illustrates how a meta-analysis of multiple transcript profiles obtained from a single tissue, the liver, can be used to evaluate relevant hypothesis and discover novel mechanisms of hormonal action. We have evaluated the differential effects of Growth Hormone (GH) and estrogen in the regulation of hepatic gender differentiated gene expression as well as the involvement of sterol regulatory element-binding proteins (SREBPs) in the hepatic actions of GH and thyroid hormone.


RESULTS
Little similarity exists between liver transcript profiles regulated by 17-alpha-ethinylestradiol and those induced by the continuos infusion of bGH. On the other hand, strong correlations were found between both profiles and the female enriched transcript profile. Therefore, estrogens have feminizing effects in male rat liver which are different from those induced by GH. The similarity between bGH and T3 were limited to a small group of genes, most of which are involved in lipogenesis. An in silico promoter analysis of genes rapidly regulated by thyroid hormone predicted the activation of SREBPs by short-term treatment in vivo. It was further demonstrated that proteolytic processing of SREBP1 in the endoplasmic reticulum might contribute to the rapid actions of T3 on these genes.


CONCLUSIONS
This report illustrates how a meta-analysis of multiple transcript profiles can be used to link knowledge concerning endocrine physiology to hormonally induced changes in gene expression. We conclude that both GH and estrogen are important determinants of gender-related differences in hepatic gene expression. Rapid hepatic thyroid hormone effects affect genes involved in lipogenesis possibly through the induction of SREBP1 proteolytic processing.
Ståhlberg
Nina
N
Department of Molecular Medicine, Karolinska Institute, 17176 Stockholm, Sweden. Nina.Stahlberg@cmm.ki.se
Merino
Roxana
R
Hernández
Luis Henríquez
LH
Fernández-Pérez
Leandro
L
Sandelin
Albin
A
Engström
Pär
P
Tollet-Egnell
Petra
P
Lenhard
Boris
B
Flores-Morales
Amilcar
A
D000818:Animals; D004997:Ethinyl Estradiol / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology; D006728:Hormones / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000502:physiology
D006728:Hormones; D014284:Triiodothyronine; D004997:Ethinyl Estradiol; D013006:Growth Hormone