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Suppression of serum LH-RH and LH in rats by an inhibitor of norepinephrine synthesis

Monoamine synthesis inhibitors have been used extensively to unravel the role of neurotransmitters in the hypothalamic regulation of pituitary LH release (Coppola, Leonardi & Lippmann, 1966; Kordon & Glowinski, 1972; Kalra, P.S. & McCann, 1973). Inhibition of tyrosine hydroxylase by -methyl-paratyrosine (Corrodi & Hansen, 1966) or dopamine-β-hydroxylase by sodium diethyldithiocarbamate (Goldstein, Anagonste, Lauber & McKereghan, 1964) blocked the preovulatory discharge of LH and ovulation (Kalra & McCann, 1974). These pharmacological agents and a brain norepinephrine depletor, U-14,624 (1-phenyl-3-(2-thiazolyl)-2 thiourea (Johnson, Boukma & Kim, 1970), have been shown to suppress the release of pituitary LH induced by ovarian steroids (Kalra, Kalra, Krulich, Fawcett & McCann, 1972; Kalra, P.S. & McCann, 1973). These results were viewed as evidence for the involvement of a hypothalamic norepinephrine system in controlling LH release as suggested by Sawyer (1952). A single intraventricular injection of 6-hydroxydopamine to deplete norepinephrine and dopamine (Kostrzewa & Jacobowitz, 1974) reduced the LH-RH content of the hypothalamus (Kalra, 1975), but little other information is available to show that the depletion of brain catecholamines, and specifically norepinephrine, by these drugs results in modification of LH-RH secretion. In the present study the inhibition of pituitary LH release by the norepinephrine depletor, U-14,624, was investigated in ovariectomized rats.