title: Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans.
abstract: The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
authors.forename: C S
authors.initials: CS
authors.lastname: Fekete
authors.forename: P H
authors.initials: PH
authors.lastname: Strutton
authors.forename: F R
authors.initials: FR
authors.lastname: Cagampang
authors.forename: E
authors.initials: E
authors.lastname: Hrabovszky
authors.forename: I
authors.initials: I
authors.lastname: Kalló
authors.forename: P J
authors.initials: PJ
authors.lastname: Shughrue
authors.forename: E
authors.initials: E
authors.lastname: Dobó
authors.forename: E
authors.initials: E
authors.lastname: Mihály
authors.forename: L
authors.initials: L
authors.lastname: Baranyi
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: P
authors.initials: P
authors.lastname: Panula
authors.forename: I
authors.initials: I
authors.lastname: Merchenthaler
authors.forename: C W
authors.initials: CW
authors.lastname: Coen
authors.forename: Z S
authors.initials: ZS
authors.lastname: Liposits
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008326:Mammillary Bodies / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000502:physiology; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D006632:Histamine; D007986:Luteinizing Hormone