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Rebecca Z. Sokol,^1,2 Saixi Wang,¹ Yu-Jui Y. Wan,³ Frank Z. Stanczyk,¹ Elisabet Gentzschein,¹ and Robert E. Chapin⁴

¹Department of Obstetrics and Gynecology and ²Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA; ³Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA; ⁴Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Abstract

Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH levels were measured in serum, and lead levels were quantified in whole blood. Hypothalamic GnRH mRNA levels were also quantified. We found no significant differences in serum LH and GnRH among the groups of animals treated within each time period. A significant dose-related increase of GnRH mRNA concentrations with lead dosing occurred in animals treated for 1 week. Animals treated for more than 1 week also exhibited a significant increase in GnRH mRNA, but with an attenuation of the increase at the higher concentrations of lead with increased duration of exposure. We conclude that the signals within and between the hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose lead exposure. Key words: gonadotropin-releasing hormone, hypothalamic-pituitary axis, lead acetate. Environ Health Perspect 110:871-874 (2002) . [Online 19 July 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p871-874sokol/ abstract.html

Address correspondence to R.Z. Sokol, Room 8K9, Women's and Children's Hospital, 1240 North Mission Road, Los Angeles, CA 90033 USA. Telephone: (323) 226-3091. Fax: (323) 226-2850. E-mail: rsokol@usc.edu

We thank the staff of the Air and Industrial Hygiene Laboratory of the California Department of the Health Services for expert blood lead analysis and G. Wolf and J. Delaney for scientific advice and technical assistance.

This research was supported by grant R01ES037649 awarded to R. Z. Sokol and by grant P30 ES07048 awarded to the University of Southern California by the National Institute of Environmental Health Sciences.

Received 22 June 2001 ; accepted 15 February 2002.