Orexin A interactions in the hypothalamo-pituitary gonadal axis.
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.
Russell
S H
SH
Imperial College School of Medicine Endocrine Unit, Hammersmith Hospital, London W12 ONN, United Kingdom.
Small
C J
CJ
Kennedy
A R
AR
Stanley
S A
SA
Seth
A
A
Murphy
K G
KG
Taheri
S
S
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D004971:Estrus / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006066:Gonads / Q000187:drug effects / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000068797:Orexins; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D002352:Carrier Proteins; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D011188:Potassium