How hormones determine the developmental pattern of neurotransmitter-specific cell types in the nervous system remains a mystery. We are studying the sexual differentiation of cholecystokinin (CCK) containing neurons in the mammalian limbic system. CCK neurons in the medial nucleus of the amygdala (MeAp) become sexually dimorphic by the second postnatal day and remain dimorphic throughout life. We have determined that thyroid hormone receptors (TRs) are expressed in abundance in the MeAp, which also contains a high density of cells that express gonadal steroid hormone receptors. The apparent density of cells in the MeAp that express mRNAs encoding TRs and sex steroid hormone receptors suggests that these ligand activated nuclear transcription factors may be co-expressed within individual cells, and may therefore interact to coordinate the development of hormone-sensitive neurons. In addition, the structural similarity between TRs and steroid hormone receptors suggests that they may also share functional similarities in the regulation of gene expression within hormone-sensitive neuronal pathways. Four principal subtypes of TRs (TRa1, TRa2, TRb1 and TRb2) have been isolated that are expressed in the brain; however, only TRa1 and TRb1and 2 have been shown to regulate gene expression in response to thyroid hormone (T3) and TRb2 shows minimal expression. On the basis of in vitro data it has been suggested that TRa2 may inhibit the action of hormone activated TRa1s and TRb1s. Thus the differential expression of TRa1 and TRa2 in developing neurons may regulate the influence of T3 on brain function and development. As a first step towards addressing this issue, we have evaluated the postnatal profile of TR mRNAs in the MeAp by using both RT-PCR and in situ hybridization and cRNA probes that are specific for the TRa1, TRa2 and TRb1 subtypes. The isolation of TR subtype specific cDNAs from Rhesus macaque will enable us to evaluate possible functional interactions between TRs and sex steroid hormone receptors in nonhuman primate brains.