Toxicology Letters, 34 (1986) 231-245 Elsevier 231 TXL 01684 FUNCTIONAL CONSEQUENCES OF PRENATAL METHYLMERCURY EX- POSURE: EFFECTS ON RENAL AND HEPATIC RESPONSES TO TROPHIC STIMULI AND ON RENAL EXCRETORY MECHANISMS THEODORE A. SLOTKIN”*, ROBERT J. KAVLOCKb, TODD COWDERYa, LISA ORBANDa, MARIA BARTOLOMEa, JACQUELINE A. GRAYb, BLAIR F. REHNBERGb and JORGE BARTOLOMEa “Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, and bHealth Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, U.S.A. (Received 19 August 1986) (Accepted 6 September 1986) SUMMARY The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal ac- tivity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In con- trast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions of urea and electrolytes and an even- tual reduction in glomerular filtration as assessed by creatinine clearance. In addition, the reactivity of the kidney to challenge with desmopressin was altered coincidentally with the appearance of the effects on basal clearance mechanisms. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs. postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity. * To whom correspondence should be addressed, at: Box 3813, Duke University Medical Center, Durham, NC 27710, U.S.A. Abbreviations: ANOVA, analysis of variance; DDAVP, desmopressin (1-deamino-8-o-arginine- vasopressin) acetate; ODC, ornithine decarboxylase. 0378.4274/86/$ 03.50 0 Elsevier Science Publishers B.V. (Biomedical Division)