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Identification of Neurokinin B-Expressing Neurons as an Highly Estrogen-Receptive, Sexually Dimorphic Cell Group in the Ovine Arcuate Nucleus¹

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT; INSERM, U-378, Institut Francois Magendie (P.C.), F33077 Bordeaux, and INRA, Station de Physiologie de la Reproduction (A.C.), 37380 Nouzilly, France

Address all correspondence and requests for reprints to: Dr. Allan E. Herbison, Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT. E-mail: allan.herbison{at}bbsrc.ac.uk

Studies were undertaken to examine the hypothesis that neurons expressing neurokinin B (NKB) may represent an estrogen-receptive input to GnRH neurons in the sheep. Cells immunoreactive for NKB were located almost exclusively within the arcuate nucleus of the ovine hypothalamus. Dual labeling experiments revealed that essentially all NKB neurons (97%) were immunoreactive for estrogen receptor and that NKB-immunoreactive fibers were found in close proximity to approximately 40% of GnRH neurons located in the rostral preoptic area as well as intermingled with GnRH fibers in the median eminence. The analysis of male and female brains revealed a marked female-dominant sex difference in the numbers of NKB neurons, and sections obtained from in utero androgen-treated females indicated that this sex difference resulted from an organizational influence of testosterone during neural development. In adult ovariectomized ewes, in situ hybridization studies failed to detect any significant effect of 8- to 26-h exposure of estrogen on cellular NKB messenger RNA levels. Together, these studies identify the first sexually differentiated neuronal cell population in the ovine hypothalamus and, remarkably, show that essentially all of these female-dominant NKB neurons express estrogen receptors. Although these neurons may be involved in any number of steroid-dependent, sexually differentiated functions in the sheep, the neuroanatomical evidence for potential NKB inputs to GnRH neurons suggests a role for this novel population in the regulation of reproductive function.

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