Reproductive Toxicology, Vol.7, pp. 237-248, 1993 0890-6238/93 $6.00 + .00 Printedin the U.S.A.All rightsreserved. Copyright© 1993Pergamon Press Ltd. • Original Contribution ESTROGENIC AND ANTIESTROGENIC ACTIONS OF PCBs IN THE FEMALE RAT: IN VITRO AND IN VIVO STUDIES HEIKO T. JANSEN,* PAUL S. COOKE,* JOHN PORCELLI,* TSUEI-CHu LIU,'~ and LARRY G. HANSEN* *Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, Illinois; and tDepartment of Medical Technology, National Yang Ming Medical College, Shih-Pai, Taipei, Taiwan, Republic of China Abstract m A series of studies were performed to examine the effects of various PCB congeners [3,4,3',4'- TCB (PCB77), 2,5,2',5'-TCB (PCB52), 4' OH-2,4,6-TCB (OHPCB)] and a complex PCB mixture (Aroclor 1242; A1242) on the weights and patterns of cell proliferation of immature rat uteri in vivo and the effects of A1242 on gonadotropin release by dispersed anterior pituitary cells in vitro. Immature (20-day) rats were treated ip with corn oil (vehicle), PCBs, or 17/l-estradiol (E2) once or daily for two consecutive days. Except for PCB77, all PCBs and E2 produced significant increases in uterine weights (P < 0.01) and increases in uterine 3H-thymidine labeling. PCB77 attenuated (P < 0.01) the increase in uterine weight due to either A1242 or E2 treatment. Cultured anterior pituitary cells exposed to varying concentrations of A1242 (0.1 to 50 ppm) exhibited enhanced gonadotropin responses to gonadotropin-releasing hormone (GnRH) similar to that of E2. These results demonstrate that PCBs can produce either estrogenic or antiestrogenic effects. Key Words: polychlorinated biphenyls;rat; pituitary; uterus; gonadotropins;estrogen;antiestrogen;female. INTRODUCTION Polychlorinated biphenyls (PCBs) belong to a large group of persistent environmental contaminants known to produce adverse reproductive effects in the female (I). For example, mice, rats, and mon- keys treated with PCBs exhibit significantly longer estrous cycles and/or anovulation (2-4). Reduc- tions in the percent of ova implanted and in the number of ovarian follicles have also been docu- mented (2,5). Neonatal treatment with Aroclor 1221 (a PCB mixture containing 21% C1) induces preco- cious puberty, persistent vaginal estrus, and prema- ture reproductive quiescence (6), and another PCB mixture, Aroclor 1254, produces complete repro- ductive failure when given to mink (7). Presented in part at the 72nd annual meeting of the Endo- crine Society, Atlanta, GA, June 1990 and at the 25th annual meeting of the Society for the Study of Reproduction, Raleigh, NC, July, 1992. Address correspondence to Heiko T. Jansen, Department of Veterinary Biosciences, University of Illinois, 2001 S. Lincoln, Urbana, IL 61801 Received 8 September 1992; Revision received 17 November 1992; Accepted 21 November 1992. 237 Certain PCB congeners, putative PCB metabo- lites, and complex PCB mixtures (<48% chlorine content) are estrogenic and bind competitively to estrogen receptors (8-10) leading to increases in uterine weight (6,9-11). These estrogenic effects of PCBs are potentially deleterious to a variety of re- productive organs, as shown by extensive earlier work indicating that exposure to naturally occurring or synthetic estrogens (e.g., coumestral, DDT, methoxychlor, and chlordecone) can lead to repro- ductive abnormalities (12,13). While the estrogenic PCBs may have direct ef- fects on reproductive organs such as the ovary (5,14) and uterus (6,8-11), some of these reproduc- tive effects may result from the actions of PCBs on the pituitary and/or hypothalamus. These effects could lead to changes in luteinizing hormone (LH) or follicle-stimulating hormone (FSH) secretion and thereby cause secondary changes in gonadal func- tion. However, little information exists regarding possible direct influences of PCBs on pituitary func- tion. The accumulation of certain PCBs within the pituitary (15) suggests that this may be a site of PCB action and this could explain some of the observed alterations in reproductive function. Both hypotha-