EXPRESSION OF THE ORPHAN RECEPTOR STEROIDOGENIC FACTOR-I MESSENGER-RNA IN THE RAT MEDIAL BASAL HYPOTHALAMUS

Steroidogenic factor-1 (SF1), an orphan receptor of the nuclear hormon e receptor family, binds to the AAGGTCA motif in the promoter elements of several diverse target genes, including some that mediate steroido genesis and sexual differentiation. In addition, SF-1 is expressed in embryonic forebrain, suggesting that it plays a role in neural develop ment. This study was undertaken to study the distribution and regulati on of SF-1 mRNA expression in the rat brain. SF-1 mRNA levels were mea sured in tissue dissections by ribonuclease protection assay. A 452 nt P-32-labeled cRNA probe, complementary to the putative ligand-binding domain of the rat SF-1 mRNA, was synthesized from the rat SF-1 cDNA i nserted into pBluescript II KS, using a Sty 1 fragment and T3 polymera se. The probe protected a single 390 nt transcript in the medial basal hypothalamus (MBH) and peripheral steroidogenic tissues of the male r at. The size of this protected band corresponded to that of the protec ted sense RNA standard (HindIII fragment of the SF-1 cDNA transcribed with T7 polymerase). No SF-1 mRNA was detected in the preoptic area, a mygdala or cingulate cortex. The levels of SF-1 mRNA in MBH were not a ffected by gonadectomy or androgen treatment, nor was there a sex diff erence in its expression in adults. In situ hybridization histochemist ry revealed that SF-1 was localized to the ventromedial nucleus of the adult hypothalamus. The levels of SF-1 mRNA were high on gestational day is after which they fell by similar to 30% and remained constant t hroughout gestation, the first week of neonatal life, and into adultho od. These results demonstrate that the gene encoding SF-1 is expressed in a discrete region of the rat hypothalamus and appears to be develo pmentally regulated but not affected by gonadal hormones in adults.