Growth hormone (GH) binding to its receptor modulates gene transcription by inf luencing the amount or activity of transcription factors. In the rat, GH exerts sexually dimorphic effects on liver gene transcription through its pattern of secretion which is intermittent in males and continuous in females. The expression of the CYP2C12 gene coding for the female-specific cytochrome P450 2C12 protein is dependent on the continuous exposure to GH. To identify the transcription factor(s) that mediate(s) this sex-dependent GH effect, we studied the interactions of the CYP2C12 promoter with liver nuclear proteins obtained from male and female rats and from hypophysectomized animals treated or not by continuous GH infusion. GH treatment induced the binding of a protein that we identified as hepatocyte nuclear factor (HNF) 6, the prototype of a novel class of homeodomain transcription factors. HNF-6 competed with HNF-3 for binding to the same site in the CYP2C12 promoter. This HNF-6͞ HNF-3 binding site conveyed both HNF-6-and HNF-3-stimulated transcription of a reporter gene construct in transient cotransfection experiments. Electrophoretic mobility shift assays showed more HNF-6 DNA-binding activity in female than in male liver nuclear extracts. Liver HNF-6 mRNA was barely detectable in the hypophysectomized rats and was restored to normal levels by GH treatment. This work provides an example of a homeodomain-containing transcription factor that is GH-regulated and also reports on the hormonal regulation of HNF-6.

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Several metabolic processes in the liver are regulated by thyroid hormone (T3). Gene expression profiles of livers from normal and TRbeta-deficient mouse strains should allow the classification of rapid and sustained effects of T3, as well as identification of target genes that are dependent on TRbeta. The immediate and long-term T3 regulation of about 4000 genes in livers from hypo- and hyperthyroid wild-type and TRbeta-deficient mice was analyzed using cDNA microarrays. T3 was found to regulate more than 200 genes, and among these, more than 100 were previously not described. Sixty percent of all these genes show dependence on the TRbeta gene for T3 regulation, indicating that TRalpha1 may have previously unknown functions in the liver. Analysis of the gene expression patterns showed a clear functional distinction between rapid (2 h) actions of T3 and late effects, seen after 5 d of sustained T3 treatment. Many metabolic actions were rapidly executed, whereas effects on mitochondrial function, for example, were seen after the sustained T3 treatment. As compared with wild-type controls, TRbeta-/-mice exhibited elevated expression of some target genes and reduced levels of others, indicating that both direct and indirect gene regulation by TRs in liver is complex and involves both ligand-dependent and -independent actions by the major TR isoforms.

We received 2 stranded loggerhead sea turtles (Caretta caretta) with squamous cell carcinomas to necropsy. The dead turtles had been collected in Gran Canaria and Fuerteventura in April 1994 and May 1997, respectively to determine the cause of death. One turtle had 3 ulcerated lesions in the dorsal part of the neck and several irregular masses in the lungs and kidneys. Histologic examination of lesions in the skin, lungs, kidneys, and ventricular myocardium revealed neoplastic proliferation of abnormal keratinocytes. Ultrastructural examination identified the tumoral cells as epithelial cells. The second turtle had 4 lesions in the skin of the head and flippers, and several irregular masses in the lungs, liver, and kidneys. Histological examination revealed a squamous cell carcinoma with metastases to muscle tissue, liver, lungs, and kidneys. Attempts to characterize the tumoral cells by immunohistochemistry using several monoclonal and polyclonal antisera against high and low molecular weight cytokeratins from mammals, as well as vimentin and desmin, failed. Differences between reptilian keratins (mainly β-keratins) and mammalian keratins (mainly α-keratins) could explain this absence of immunoreactivity. This is the first description of squamous cell carcinoma in sea turtles. KEY WORDS: Squamous cell carcinoma · Loggerhead turtle · Caretta caretta · Sea turtle · Reptile · Immunohistochemistry Resale or republication not permitted without written consent of the publisherDis Aquat Org 58: [245][246][247][248][249][250] 2004 of 20 to 30 turtles per year. We report here the histopathological features of 2 cases of metastasizing squamous cell carcinoma in the loggerhead sea turtle Caretta caretta. MATERIALS AND METHODSWithin a 3 yr period (i.e. in April 1994 and May 1997), 2 stranded loggerhead sea turtles with squamous cell carcinomas were submitted to the Veterinary Faculty, ULPGC. The first was a 6.5 kg juvenile female stranded in Gran Canaria (27°40' N, 15°20' W). The turtle had a curved carapace length and width of 33 and 31 cm respectively, and a straight carapace length and width of 29 and 28 cm respectively. After stranding, the turtle had been housed in an aquarium at the Wildlife Rehabilitation Center of Tafira, Gran Canaria. Physical examination had revealed anorexia and lethargy. Despite forcefeeding and intramuscular administration of antimicrobial enrofloxacin, the turtle died 1 wk after stranding. The second turtle was a 7.2 kg juvenile female found stranded dead in Fuerteventura (28°10' N, 14°20' W). This turtle had a curved carapace length and width of 34 and 33 cm respectively, and a straight carapace length and width of 31 and of 30 cm respectively.The gross postmortem examinations of both turtles were carried out using the protocol developed by Wolke & George (1981). Fecal specimens were processed following techniques described by Boch & Supperer (1982).Macroscopic lesions were recorded and tissue samples from all major organs were fixed in 10% neutral buffered formalin, embedded i...

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