Orexin A interactions in the hypothalamo-pituitary gonadal axis

The distribution of orexin A-immunoreactive neurons and orexin type I recep tors in the CNS suggests important roles in regulating the hypothalamo-pitu itary gonadal (HPG) axis and sexual behaviors. We examined orexin A interac tions in the HPG axis in vivo and in vitro. Orexin A stimulated LH-releasin g hormone (LHRH) release in hypothalamic explants harvested from male rats (+133%) and from females at proestrus (+233%), with no effect at estrus or metestrus. Orexin A dose dependently inhibited LHRH-stimulated LH release i n dispersed pituitaries from proestrous females only. A selective NPY1-rece ptor antagonist abolished in vitro release of LHRH by orexin A. Hyperestrog enization in female rats reduced orexin A content in hypothalamus (-28%), m idbrain (-26%), medulla (-40%), thalamus (-36%), olfactory tubercles (-25%) , and cortex (-35%), brain regions that are important in HPG control and se x-cycle specific behaviors. Orexin A content was lower in hypothalamus (-20 %) and higher in midbrain (+40%), medulla (+31%), and thalamus (+33%) at la te proestrus vs. other cycle stages. Orexin A release after administration of 56 mm KCI was significantly greater in hypothalamic explants harvested o n the morning of proestrus than at estrus or metestrus, and orexin A releas e was stimulated by estradiol (E2) in explants from males. These results re veal important interactions for orexin A in the HPG axis.