Abstract
Small heterodimer partner (SHP; NR0B2) is a member of the large nuclear receptor family of transcriptional factors that lacks a conventional DNA binding domain. Various studies have reported SHP to be a repressor of transcriptional activities of a number of nuclear receptors, including glucocorticoid receptor, estrogen receptor, androgen receptor, thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, constitutive androstane receptor, pregnane X receptor, HNF4α, liver receptor homologue 1, estrogen-related receptor-γ, Nur77 and liver X receptor (LXR). The very broad range of receptors sensitive to inhibition by SHP suggests a central role for SHP in modulation of nuclear receptor signaling pathways. SHP is expressed in a wide variety of tissues, including heart, brain, liver, spleen, adrenal gland, small intestine, and pancreas. Moreover, human SHP gene is located on chromosome 1p36.1 and consists of two exons separated by an intron. SHP gene transcription is regulated by several members of the nuclear receptor superfamily including the bile acid receptor farnesoid X receptor, steroidogenic factor-1, HNF4α, liver receptor homologue 1, estrogen receptor and estrogen-related receptor-γ. Recent progresses on the elucidation of molecular mechnism of SHP gene expression and function will give us a chance to develop new drug therapies treating a variety of human diseases including diabetes, obesity and disorder of lipid and cholesterol metabolism. [J Physiol Sci. 2006;56 Suppl:S17]
