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BLOCKADE OF OVULATION IN THE RAT BY THE FUNGICIDE SODIUM N-METHYLDITHIOCARBAMATE: RELATIONSHIP BETWEEN EFFECTS ON THE LUTEINIZING HORMONE SURGE AND ALTERATIONS IN HYPOTHALAMIC CATECHOLAMINES
Citation:
Goldman, J., T. Stoker, R. Cooper, W. McElroy, AND J. Hein. BLOCKADE OF OVULATION IN THE RAT BY THE FUNGICIDE SODIUM N-METHYLDITHIOCARBAMATE: RELATIONSHIP BETWEEN EFFECTS ON THE LUTEINIZING HORMONE SURGE AND ALTERATIONS IN HYPOTHALAMIC CATECHOLAMINES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/106, 1994.
Description:
Sodium N-methyldithiocarbamate (SMD), also known as metam sodium, is a commonly employed soil fungicide and nematocide. Structurally related dithiocarbamates have been found to decrease norepinephrine (NE) synthesis by suppressing the activity of dopamine-B-hydroxylase. Since brain hypothalamic catecholamine (CA) activity is involved in generating the proestrus afternoon surge in blood luteinizing hormone (LH) which stimulates the final stages of ovulation, this study explored the effect of SMD on this hormonal trigger and its relationship to changes in hypothalamic CAs. Ovariectomized, steroid-primed Long-Evans rats showed a dose-related (25-100 mg/kg, i.p.) suppression of the surge and a drop in NE when SMD was given at 1100 h, a few hrs prior to the expected LH rise. With cycling rats, a decline with dose (50-300 mg/kg, 1200 h, proestrus) was seen in the percentage of ovulating females, with earlier injections (0900 h) being less effective at the highest dose. Anterior and posterior hypothalamic NE fell by 3 hrs post-injection and was accompanied by a rise in dopamine. Although there was a distinct parallel between the alterations in regional CAs and the incidence of ovulation at the high doses of SMD, the relationship did not hold as the dose decreased. A similar dissociation between ovulation and CAs was seen when equimolar doses of SMD or methylisothiocyanate, a principal metabolite, were given by gavage. At the level of regional analysis employed, the data indicate that while i.p. injections of SMD are able to block the LH surge and ovulation in female rats, the mechanism of action may not be strictly dependent on the ability of this compound to alter the metabolism of hypothalamic CAs.