Leptin is involved in the hypothalamic control of food intake and body weight. Fos immunohistochemistry has been used to functionally map leptin target neurons involved in these regulatory processes. However, only a subset of hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb) also coexpress the neuronal activation marker Fos after leptin stimulation. To functionally map all leptin target neurons, regardless of whether leptin-mediated neuronal activation or inhibition occurs, we immunohistochemically investigated the leptin-induced nuclear translocation of the signal transducer and activator of transcription molecule STAT3, which represents a crucial step in the regulation of leptin-dependent gene expression. As proven by colocalization studies with the nuclear 4Ј,6-diamidino-2-phenylindole dilactate stain, intracerebroventricular leptin treatment, but not intracerebroventricular application of pyrogen-free saline, induced a time-dependent nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei, with strong nuclear STAT3 signals detectable in the arcuate nucleus, the lateral hypothalamus, and the ventromedial and dorsomedial hypothalamic nuclei. This leptininduced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. Combined immunohistochemical STAT3 and Fos detection after leptin treatment revealed a higher number of STAT3-positive than Fos-positive cell nuclei in the aforementioned hypothalamic structures and showed that Fos immunoreactivity colocalized only in a subset of all leptinresponsive STAT3 nuclei. These results suggest that the detection of nuclear STAT3 immunoreactivity represents a new neuroanatomical tool to functionally map central leptin actions. They further support the importance of ventrally located caudal hypothalamic structures representing the main leptin targets involved in body weight regulation.

7-Acetyl-1,1,3,4,4,6-hexamethyl- 1,2,3,4-tetra-hydronaphthaline (AHTN) is one of the two most widely used fragrances of a group of substances known collectively as the polycyclic musks. In the last few years evidence has been accumulating that AHTN is hepatotoxic when administered at high doses. In the present study the subchronic hepatotoxicity of AHTN administered to rats at doses within the human exposure range was evaluated. For this purpose female and male juvenile Wistar rats were exposed to AHTN (300 microg/kg body weight per day, i.p.) alone or to a single dose of diethylnitrosamine (DEN) (100 mg/kg body weight, i.p.) followed by AHTN (1, 10, 100 or 300 microg/kg body weight per day, i.p.) for 90 days. Thereafter the liver architecture as well as the presence of placental glutathione S-transferase (GST-P)-positive hepatic lesions was assessed. In male animals receiving AHTN alone or in combination with DEN the number of GST-P-positive single hepatocytes was similar to that in untreated rats, while GST-P-positive mini-foci and foci were not observed. In the case of female rats the number of GST-P-positive single hepatocytes and mini-foci in AHTN-treated rats was similar to that in untreated animals, whereas in those animals receiving AHTN either alone or in combination with DEN, GST-P-positive foci could not be detected or were present in a number as similar to that in untreated rats. In conclusion, in the present study it has been shown that AHTN administered over a 90-day period in concentrations similar to those taken up daily by humans does not lead to hepatotoxicity.