OPIOID PRECURSOR GENE-EXPRESSION IN THE HUMAN HYPOTHALAMUS

Using in situ hybridization histochemistry, we studied the distributio n of neurons that express preproopiomelanocortin (pre-POMC), preprodyn orphin (pre-PDYN), and preproenkephalin (pre-PENK) gene transcripts wi thin the human hypothalamus and surrounding structures. Of the three o pioid systems, pre-POMC neurons have the most restricted distribution. Pre-POMC cells are most numerous in the infundibular nucleus and retr ochiasmatic area of the mediobasal hypothalamus; a few labeled cells a re present within the boundaries of the ventromedial nucleus and infun dibular stalk. Pre-POMC message was not found in the limited samples o f structures adjacent to the hypothalamus. In contrast to neurons that express pre-POMC, neurons expressing pre-PDYN and pre-PENK are more w idely represented throughout the hypothalamus and extrahypothalamic st ructures. However, pre-PDYN and pre-PENK cells differ from one another in distribution. Pre-PDYN message is especially abundant in neurons o f the tuberal and mammillary regions, with a distinct population of la beled cells in the premammillary nucleus and dorsal posterior hypothal amus. Pre-PDYN gene expression also is found in neurons of the dorsome dial nucleus, ventromedial nucleus, caudal magnocellular portion of th e paraventricular nucleus, dorsolateral supraoptic nucleus, tuberomamm illary nucleus, caudal lateral hypothalamus, and retrochiasmatic area. In structures immediately adjacent to the hypothalamus, pre-PDYN neur ons were observed in the caudate nucleus, putamen, cortical nucleus of the amygdala, and bed nucleus of the stria terminalis. Pre-PENK neuro ns occur in varying numbers in all hypothalamic nuclei except the mamm illary bodies. The chiasmatic region is particularly rich in pre-PENK neurons, with the highest packing density in the intermediate nucleus [the intermediate nucleus (Braak and Braak [1987] Anat. Embryol. 176:3 15-330) has also been termed the sexually dimorphic nucleus of the pre optic area (SDA-POA; Swaab and Fliers [1985] Science 228:1112-1115) or the interstitial nucleus of the anterior hypothalamus 1 (Allen et al. [1989] J. Neurosci. 9:497-506)], dorsal suprachiasmatic nucleus, medi al preoptic area, and rostral lateral hypothalamic area. Pre-PENK neur ons are numerous in the infundibular nucleus, ventromedial nucleus, do rsomedial nucleus, caudal parvicellular portion of the paraventricular nucleus, tuberomammillary nucleus, lateral hypothalamus, and retrochi asmatic area. Only a few lightly labeled cells were found in the perip hery of the supraoptic nucleus and lateral tuberal nucleus. In areas a djacent to the hypothalamus, cells that contain pre-PENK message occur in the nucleus basalis of Meynert, central nucleus of amygdala, bed n ucleus of the stria terminalis, caudate nucleus, and putamen. The diff erential distribution of pre-POMC, pre-PDYN, and pre-PENK neurons in t he human hypothalamus suggests that these three opioid systems influen ce hypothalamic functions in quite different ways. (C) 1995 Wiley-Liss , Inc.