Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats David Gunnarsson a,b , Gunnar Nordberg a , Per Lundgren b , Gunnar Selstam b,  a Department of Public Health and Clinical Medicine, Unit of Environmental Medicine, Umea ˚ University, 901 87 Umea ˚, Sweden b Department of Molecular Biology, Umea ˚ University, 901 87 Umea ˚, Sweden Received 25 March 2002; received in revised form 21 May 2002; accepted 25 July 2002 Abstract Cadmium (Cd) is a widespread environmental pollutant, characterized by its ability to affect various organs. Adverse effect of Cd on the testis including decreased testosterone production are well-known phenomena, but the cellular events explaining these effects have not yet been established. In the present study the initial steps of gonadotropin mediated testosterone biosynthesis were examined in vivo in rats, in relation to Cd dose and time after injection. In the dose  /response experiment Male Sprague  /Dawley rats received a single subcutaneous (sc) injection of CdCl 2 (1, 5 or 10 mmol/kg body weight) and were sacrificed 48 h after injection. A statistically significant decrease in luteinizing hormone (LH) receptor mRNA level in the testicular tissue was demonstrated at the highest dose (10 mmol/kg). In the temporal  / response experiment rats were given 10 mmol/kg of CdCl 2 sc and sacrificed 0.48, 4.8, 48 or 144 h after injection. LH receptor mRNA levels as well as cyclic adenosine monophosphate (cAMP) levels were found to be significantly lowered at 48 and 144 h. These observations of the mechanisms whereby Cd exerts its effect on the initial steps of testosterone biosynthesis are the first from in vivo experiments. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cadmium; Luteinizing hormone receptor; Cyclic adenosine monophosphate system; Steroidogenesis; Rat; Testis 1. Introduction Cadmium (Cd) is a widespread, highly toxic environmental pollutant. Cd accumulates in bio- logical systems and because of its long biological half-life in humans it accumulates with advancing age (Nordberg, 1974). The flow of Cd in ecological systems increases, due to human contamination by major sources as mining, smelting and industrial use. Sources for humans of this metal also include food, cigarette tobacco and alcoholic beverages (Nordberg, 1974; Paksy et al., 1997; Ja ¨rup et al., 1998). It is well established that acute Cd administra- tion affects male as well as female reproductive organs of rodents. Some of the effects found in laboratory experiments are testicular necrosis and sterility in male rats (Parizek and Zahor, 1956; Nordberg, 1971; Piasek and Laskey, 1999), whereas in female rats the estrous cycle is altered  Corresponding author. Tel.:  /46-90-786-56-27 E-mail address: gunnar.selstam@molbiol.umu.se (G. Selstam). Toxicology 183 (2003) 57  /63 www.elsevier.com/locate/toxicol 0300-483X/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0300-483X(02)00440-7