Steroidogenic Factor 1 Messenger Ribonucleic Acid Expression in Steroidogenic and Nonsteroidogenic Human Tissues: Northern Blot and in Situ Hybridization 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.

Developmental expression of steroidogenic factor-1, cyp19a1a and cyp19a1b from common carp (Cyprinus carpio)

“…4). This finding is consistent with previous reports in humans and rats (Ramayya et al, 1997;Morohashi et al, 1999). In carp, SF-1 mRNA is only expressed abundantly in the liver of females, but not in males (Fig.…”

The effect of human GATA4 gene mutations on the activity of target gonadal promoters

“…In endocrine cells, we and others have shown that the nuclear receptors NR5A1 and NR5A2 are important transcriptional partners for GATA4 (Viger et al 2008). Although NR5A1 is expressed in the heart, at least at the transcript level (Ramayya et al 1997, Nishimura et al 2004, there is currently no evidence for a functional role for this receptor as a transcriptional partner for GATA4 in this tissue. Unlike TBX5 in the heart (Garg et al 2003), the functional synergism between the G295S mutant and its gonadal partners NR5A1 and NR5A2 was not compromised (Fig.…”

NR5A1 (nuclear receptor subfamily 5, group A, member 1)

“…SF-1 is expressed in tissues involved in steroid hormone production and reproductive function, i.e. the three layers of the adrenal cortex, testicular Leydig and Sertoli cells, ovarian interstitium, theca and granulosa cells, and, to a lesser degree, corpus luteum Ikeda et al, 1993;Morohashi et al, 1994;Ramayya et al, 1997;Morohashi, 1999). SF-1 is also expressed in non-steroidogenic tissues like pituitary gonadotropes.…”

“…SF-1 is also expressed in non-steroidogenic tissues like pituitary gonadotropes. It is also expressed in the dorsomedial portion of the ventromedial hypothalamus (VMH) Shinoda et al, 1995), in the endothelial linings of the venous sinuses and pulp veins in the spleen (Ramayya et al, 1997;Morohashi et al, 1999), and in a subset of hippocampal neurons. It has been described that in developing human embryos SF-1 represents the earliest marker of adrenogonadal differentiation, first appearing in the urogenital ridge Morohashi et al, 1995;Hanley et al, 1999;Hanley et al, 2001).…”