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ToxSci Advance Access originally published online on September 26, 2003
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Toxicological Sciences 77, 35-40 (2004)
Copyright © 2004 by the Society of Toxicology

ENDOCRINE TOXICOLOGY

The Effects of Low-level Pb on Steroidogenic Acute Regulatory Protein (StAR) in the Prepubertal Rat Ovary

Vinod Srivastava, Robert K. Dearth, Jill K. Hiney, Lisa M. Ramirez, Gerald R. Bratton and W. Les Dees1

Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas 77843-4458

Estradiol (E2) is suppressed in prepubertal females exposed maternally to lead (Pb); thus, we assessed effects of Pb on ovarian steroidogenic acute regulatory protein (StAR) as a potential mechanism for this action. Adult Fisher 344 females were dosed with 12 mg of lead acetate per ml of Pb acetate (PbAc) or sodium acetate (NaAc; control), beginning 30 days prior to breeding and continuing until their pups were weaned. For the first part of this study, animals from both groups were killed when 31 days old, at 0800 h, for assessment of basal ovarian StAR gene expression. Results indicated Pb decreased (p < 0.01) both StAR transcripts. In the second part of the study, pregnant mare serum gonadotropin (PMSG) was administered to half of the Pb-treated and control animals at 0800 h. These animals, and animals from both groups that did not receive PMSG, were killed and ovaries and blood collected at 1600 h to assess ovarian StAR protein and E2 responsiveness to gonadotropin stimulation. Pb decreased (p < 0.0001) basal StAR protein expression and lowered (p < 0.001) E2 levels in animals that did not receive PMSG. PMSG induced (p < 0.0001) StAR protein in both the Pb-treated and control animals, an action associated with increased (p < 0.001) serum levels of E2. These results are the first to show that Pb alters basal StAR synthesis, but does not alter gonadotropin-stimulated StAR synthesis, hence, suggesting the primary action of Pb to suppress E2 is through its known action to suppress the serum levels of luteinizing hormone and not due to decreased responsiveness of StAR synthesizing machinery.

Key Words: lead (Pb) toxicity; steroidogenic acute regulatory protein; pubertal development; Fisher 344 rats; luteinizing hormone; estradiol.


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