Orexin A interactions in the hypothalamo-pituitary gonadal axis

Sabina H. Russell, Caroline J. Small, Adam R. Kennedy, Sarah A. Stanley, Asha Seth, Kevin G. Murphy, Shahrad Taheri, Mohammad A. Ghatei, Stephen R. Bloom

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The distribution of orexin A-immunoreactive neurons and orexin type I receptors in the CNS suggests important roles in regulating the hypothalamo-pituitary gonadal (HPG) axis and sexual behaviors. We examined orexin A interactions in the HPG axis in vivo and in vitro. Orexin A stimulated LH-releasing 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 in dispersed pituitaries from proestrous females only. A selective NPY1-receptor antagonist abolished in vitro release of LHRH by orexin A. Hyperestrogenization in female rats reduced orexin A content in hypothalamus (-28%), midbrain (-26%), medulla (-40%), thalamus (-36%), olfactory tubercles (-25%), and cortex (-35%), brain regions that are important in HPG control and sex-cycle specific behaviors. Orexin A content was lower in hypothalamus (- 20%) and higher in midbrain (+40%), medulla (+31%), and thalamus (+33%) at late proestrus vs. other cycle stages. Orexin A release after administration of 56 mM KCl was significantly greater in hypothalamic explants harvested on the morning of proestrus than at estrus or metestrus, and orexin A release was stimulated by estradiol (E2) in explants from males. These results reveal important interactions for orexin A in the HPG axis.

Original languageEnglish
Pages (from-to)5294-5302
Number of pages9
Issue number12
Publication statusPublished - 2001
Externally publishedYes


ASJC Scopus subject areas

  • Endocrinology

Cite this

Russell, S. H., Small, C. J., Kennedy, A. R., Stanley, S. A., Seth, A., Murphy, K. G., Taheri, S., Ghatei, M. A., & Bloom, S. R. (2001). Orexin A interactions in the hypothalamo-pituitary gonadal axis. Endocrinology, 142(12), 5294-5302. https://doi.org/10.1210/en.142.12.5294