Identification of neurokinin B-expressing neurons as an highly estrogen-receptive, sexually dimorphic cell group in the ovine arcuate nucleus

Studies were undertaken to examine the hypothesis that neurons expressing n eurokinin 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 experi ments revealed that essentially all NKB neurons (97%) were immunoreactive f or estrogen receptor ru and that NKB-immunoreactive fibers were found in cl ose proximity to approximately 40% of GnRH neurons located in the rostral p reoptic area as well as intermingled with GnRH fibers in the median eminenc e. The analysis of male and female brains revealed a marked female-dominant sex difference in the numbers of NKB neurons, and sections obtained from i n utero androgen-treated females indicated that this sex difference resulte d from an organizational influence of testosterone during neural developmen t. Tn adult ovariectomized awes, in situ hybridization studies failed to de tect any significant effect of 8- to 26-h exposure of estrogen on cellular NKB messenger RNA levels. Together, these studies identify the first sexual ly differentiated neuronal cell population in the ovine hypothalamus and, r emarkably, show that essentially all of these female-dominant NKB neurons e xpress estrogen receptors. Although these neurons may be involved in any nu mber of steroid-dependent, sexually differentiated functions in the sheep, the neuroanatomical evidence for potential NKB inputs to GnRH neurons sugge sts a role for this novel population in the regulation of reproductive func tion.