Steroidogenic Factor 1 Messenger Ribonucleic Acid Expression in Steroidogenic and Nonsteroidogenic Human Tissues: Northern Blot andin SituHybridization Studies

Abstract

Steroidogenic factor-1 (SF-1), a tissue-specific orphan nuclear receptor, regulates the genes of several steroidogenic enzymes, Mullerian inhibiting substance, and the gonadotrophins. Also, this transcription factor is crucial for hypothalamic, adrenal, and gonadal organogenesis in the mouse. We recently cloned the human SF-1 (hSF-1) complementary DNA (cDNA) and now report the distribution of this factor's messenger RNA (mRNA) in human tissues. Northern blot analyses of peripheral tissues revealed high hSF-1 mRNA expression in the adrenal cortex and the gonads, but no hSF-1 mRNA was detected in the placenta. High hSF-1 mRNA expression also was seen in the spleen. In this tissue, in addition to the main transcript of 3.5-4 kb seen in the adrenal and gonads, two additional transcripts of 4.4 kb and 8 kb were noted. The additional 4.4-kb transcript also was seen in several peripheral tissues and various components of the brain. However, adult liver and heart showed only the 4.4-kb transcript. In the human brain, hSF-1 mRNA expression was widespread, including several components of the limbic system. In situ hybridization studies confirmed the strong expression of hSF-1 mRNA in adrenal cortex, ovary, testis, and the spleen, primarily within reticuloendothelial cells. Thus, in the human, the hSF1 mRNA is present in both steroidogenic and nonsteroidogenic tissues, albeit not in the placenta. In the central nervous system, the expression of hSF-1 mRNA is widespread. It is composed of several different mRNA species distributed in a tissue-specific fashion. These findings suggest that hSF-1 may play a role in reticuloendothelial/immune cell maturation and/or function, as well as nervous system development and/or neurosteroid biosynthesis.

The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

“…Analysis of the predicted primary structure of TReP-132 revealed motifs characteristic of transcription factors and coactivators, which include regions rich in glutamate, proline, and glutamine residues, as well as two LXXLL motifs, suggesting the interaction of the protein with nuclear receptors (43). SF-1 and TReP-132 transcripts colocalize in many tissues, including the testis and adrenal cortex, which is consistent with their functional interaction in steroidogenesis (5,42).…”

“…It was shown in mouse and human that SF-1 is expressed at all levels of the hypothalamic-pituitary-adrenal/ gonadal axis, where it is required for the expression of diverse genes that are essential for steroid hormones biosynthesis. For instance, SF-1 is expressed in adrenal and gonadal steroid-producing cells (5,25), where it precedes P450scc gene expression (26). In these cells, SF-1 was shown to activate the expression of P450 hydroxylases (22,27,28), the ACTH receptor (29), and the gene encoding steroidogenic acute regulatory protein (StAR) (30).…”

SF1 in the Development of the Adrenal Gland and Gonads

“…It is subsequently localized to adrenal primordium (E11) and concentrated to adrenal cortical cells (E13) [13]. A similar expression pattern is seen in humans [14, 15]. In the developing gonad, SF1 participates with several other transcription factors (WT1, DAX1, SRY and SOX9) to initiate patterning of the gonad as well as differentiation of the testis.…”

Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

“…NR5A1 is expressed in steroidogenic tissues (Honda et al, 1993; Ikeda et al, 1993; Morohashi et al, 1994; Parker and Schimmer, 1997; Ramayya et al, 1997; Morohashi, 1999), pituitary gonadotrophs (Barnhart and Mellon, 1994; Ingraham et al, 1994; Ngan et al, 1999), and neurons located at the dorsomedial portion of the ventromedial hypothalamus (VMH) (Ramayya et al, 1997; Morohashi et al, 1999). In developing embryos, Nr5a1 is expressed in the urogenital ridge, representing the first marker of gonadal and adrenal differentiation (Ikeda et al, 1994; Morohashi et al, 1995, 1999; Ramayya et al, 1997; Hanley et al, 1999, 2001).…”

“…In developing embryos, Nr5a1 is expressed in the urogenital ridge, representing the first marker of gonadal and adrenal differentiation (Ikeda et al, 1994; Morohashi et al, 1995, 1999; Ramayya et al, 1997; Hanley et al, 1999, 2001). Throughout human development, NR5A1 is expressed in the steroid‐secreting adrenal cortex, in Leydig and Sertoli cells, as well as in granulosa and theca cells.…”