Topography of neurons expressing luteinizing hormone-releasing hormone gene transcripts in the human hypothalamus and basal forebrain.

The distribution of neurons expressing luteinizing hormone-releasing hormone (LHRH) gene transcripts was mapped in the human hypothalamus and basal forebrain by in situ hybridization and computer-assisted microscopy. Hypothalamic blocks were dissected from five adult males and one adult female and snap frozen in isopentane. The blocks were serially sectioned either in the coronal or in the sagittal plane at a thickness of 20 microns. Approximately every twentieth section was incubated with a 35S-labeled cDNA probe complementary to LHRH mRNA. Specificity was confirmed by hybridization of adjacent sections with a probe targeted to the gonadotropin-associated protein (GAP) region of LHRH messenger ribonucleic acids (mRNA). Maps of neurons containing LHRH mRNA were manually digitized with the aid of an image-combining computer microscope system. We report a much wider distribution and greater numbers of LHRH neurons than have been previously described in the human brain. Three morphological subtypes were observed based on cell size and labeling density: 1) small, heavily labeled, oval or fusiform neurons, located primarily in the medial basal hypothalamus, ventral preoptic area, and periventricular zone; 2) small, oval, sparsely labeled neurons located in the septum and dorsal preoptic region and scattered from the bed nucleus of the stria terminalis to the amygdala ("extended amygdala"); and 3) large round neurons (> 500 microns 2 sectional profile area), intermediate in labeling density, scattered within the magnocellular basal forebrain complex, extended amygdala, ventral pallidum, and putamen. The pronounced differences in morphology, labeling density, and location of the three subtypes suggest that distinct functional subgroups of LHRH neurons exist in the human brain.