Sex- and region-specific alterations of progesterone receptor mRNA levels and estrogen sensitivity in rat brain following developmental exposure to the estrogenic UV filter 4-methylbenzylidene camphor

Recently, we reported on in vitro and in vivo estrogenic activity of UV filters and on developmental toxicity of 4-methylbenzylidene (4-MBC) camphor [Schlumpf, M., Cotton, B., Conscience, M., Haller, V., Steinmann, B., Lichtensteiger, W., 2001 a. In vitro and in vivo estrogenicity of UV screens. Environ. Health Perspect. 109, 239; Schlumpf, M., Berger, L., Cotton, B., Conscience-Egli, M., Durrer, S., Fleischmann, I., Haller, V., Maerkel, K., Lichtensteiger, W., 2001b. Estrogen active UV screens. SOFW-J. 7, 10]. 4-MBC (7, 24, 47 mg/(kg day)) was administered in chow to long Evans rats from 10 weeks before mating of the parent (170) generation until adulthood of the F1 generation. Peripheral reproductive organs and central nervous system were studied in adult offspring. mRNA expression of progesterone receptor (PR), an estrogen-regulated gene, was investigated in medial preoptic area (MPO) and ventromedial hypothalamic nucleus (VMH) by real-time RT-PCR. We analyzed intact 12-week-old male and female offspring under steady state conditions and adult gonadectornized offspring 6 h after a single s.c. injection of estradiol-17 beta (E2) (10or50 mu g/kg) in order to assess estrogen sensitivity. At steady state conditions we observed significantly higher PR mRNA expression in VMH of control females versus control males. 4-MBC exposed females exhibited a decrease in PR mRNA to levels of control males. The increase in PR mRNA in response to E2 was higher in VMH of males of both 4-MBC groups as compared to control males. PR mRNA levels were similar in MPO of control males and females. Developmental 4-MBC exposure increased PR mRNA levels in male MPO, but did not significantly change female levels. The acute response to the lower E2 dose was decreased in MPO of 4-MBC-exposed males, whereas females of the 7 mg/kg dose group exhibited an increased reaction to 50 mu g/kg of E2. Our data indicate that developmental exposure to endocrine active chemicals such as the UV filter 4-MBC can interfere with sexually dimorphic gene expression in brain in a sex- and region-specific manner. (c) 2005 Elsevier B.V. All rights reserved.