The Oct-2 POU domain gene in the neuroendocrine brain: A transcriptional regulator of mammalian puberty

POU homeodomain genes are transcriptional regulators that control developme nt of the mammalian forebrain. Although they are mostly active during embry onic life, some of them remain expressed in the postnatal hypothalamus, sug gesting their involvement in regulating differentiated functions of the neu roendocrine brain. We show here that Oct-2, a POU domain gene originally de scribed in cells of the immune system, is one of the controlling components of the cell-cell signaling process underlying the hypothalamic regulation of female puberty. Lesions of the anterior hypothalamus cause sexual precoc ity and recapitulate some of the events leading to the normal initiation of puberty. Prominent among these events is an increased astrocytic expressio n of the gene encoding transforming growth factor-alpha (TGF alpha), a trop ic polypeptide involved in the stimulatory control of LHRH secretion. The p resent study shows that such lesions result in the rapid and selective incr ease in Oct-2 transcripts in TGF alpha-containing astrocytes surrounding th e lesion site. In both lesion-induced and normal puberty, there is a prefer ential increase in hypothalamic expression of the Oct-as and Oct-ac alterna tively spliced messenger RNA forms of the Oct-2 gene, with an increase in 2 a messenger RNA levels preceding that in 2c and antedating the peripubertal activation of gonadal steroid secretion. Both Oct-2 and 2c trans-activate the TGF alpha gene via recognition motifs contained in the TGF alpha gene p romoter. Inhibition of Oct-2 synthesis reduces TGF alpha expression in astr oglial cells and delays the initiation of puberty. These results suggest th at the Oct-2 gene is one of the upstream components of the glia to neuron s ignaling process that controls the onset of female puberty in mammals.