Oestrogen upregulates noradrenaline release in the mediobasal hypothalamus and tyrosine hydroxylase gene expression in the brainstem of ovariectomized rhesus macaques

Noradrenaline plays a key role in the initiation of ovulation in nonprimate species. A similar noradrenaline role in the primate has not been established experimentally. We utilized the ovariectomized-oestrogen-supplemented (OVX + E) rhesus macaque to examine the effects of intravenous (i.v.) infusion of oestradiol-17β(E ₂) on the activity of the brain noradrenaline system. Experiment 1 established the induction of a preovulatory surge-like release of luteinizing hormone in OVX+E monkeys by i.v. infusion of E ₂ (OVX+E+E ₂). In experiment 2, a marked increase in hypothalamic microdialysate noradrenaline concentrations occurred after identical E ₂ infusion into the OVX + E monkeys that were used in experiment 1. In experiment 3, tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus of the brainstem increased at various times after E ₂ infusion as determined by semiquantitative in situ hybridization. The amount of TH mRNA in OVX + E + E ₂ animals was higher (P < 0.05) than that in either the OVX + E or OVX monkeys; no difference was found in the latter two groups. Moreover, selected locus coeruleus sections from E ₂-infused monkeys were examined for the localization of oestrogen receptors (ER) by in situ hybridization. Both ER-α and ER-β mRNAs were expressed in the locus coeruleus, although the expression was greater for ER-α than for ER-β. We conclude that i.v. infusion of E ₂, which induces a preovulatory surge-like release of LH, stimulates brain noradrenaline activity; this enhanced activity likely involves an ER-mediated process and is reflected by hypothalamic noradrenaline release and locus coeruleus TH mRNA expression. The results support the concept that noradrenaline can influence the E ₂-stimulated ovulation in nonhuman primates and that the brainstem is one of the components in this neuroendocrine process.