Regulator of sex-limitation (Rsl) encodes a pair of KRAB zinc-finger genes that control sexually dimorphic liver gene expression.

Sexually dimorphic expression of a broad array of liver proteins involved in reproduction and xenobiotic metabolism is induced at puberty by sex-specific growth hormone patterns. An additional control of sex-dependent gene expression is conferred by Regulator of sex-limitation (Rsl) alleles. In variant rsl mice, females inappropriately express the male Sex-limited protein, Slp.

The regulator of sex-limitation gene, rsl, enforces male-specific liver gene expression by negative regulation.

Expression of a broad array of proteins is sexually dimorphic in rodent liver, dependent on sex-specific patterns of GH secretion. Mice carrying rsl (regulator of sex limitation) alleles, discovered as trans-acting loci affecting the mouse sex-limited protein (Slp) gene, reveal an additional axis in male-specific gene regulation. Slp expresses in adult males, but in rsl homozygous mice, Slp is also expressed in females.

Activation of the Ah receptor by tryptophan and tryptophan metabolites.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a variety of hydrophobic natural and synthetic chemicals, including the environmental contaminant 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). A variety of indole-containing chemicals, such as indole-3-carbinol, indolo[3, 2-b]carbazole, and UV photoproducts of tryptophan (TRP), have previously been identified as ligands for AhR. Here we have examined the ability of endogenous metabolites of tryptophan (TRP) to bind to and activate AhR in vitro and in cells in culture.

Brevetoxin-6 (PbTx-6), a nonaromatic marine neurotoxin, is a ligand of the aryl hydrocarbon receptor.

Brevetoxins (PbTx) are a family of marine polyether toxins that exert their toxic action by activating voltage-sensitive sodium channels. Two forms of brevetoxin, PbTx-2 and -3, induce hepatic cytochrome P4501A1, measured as ethoxyresorufin O-deethylase (EROD) activity, in redfish and striped bass. P4501A1 induction is transcriptionally regulated through the binding of a ligand, typically a planar aromatic compound, to the aryl hydrocarbon receptor (AhR) and subsequent complex formation with the dioxin response element (DRE), an upstream regulatory region of the CYP1A1 gene.

Ah-receptor-dependent modulation of gene expression by aged and diluted sidestream cigarette smoke.

Cigarette smoke is known to induce cytochrome P4501A1 expression and activity in a variety of species. Although the elevation of this isozyme is assumed to be associated with the activation of the CYP1A1 gene through a ligand-mediated mechanism involving the Ah-receptor (AhR), this has not been determined. In this study we have examined the mechanism by which an ambient level of aged and diluted sidestream cigarette smoke (ADSS) induces cytochrome P4501A1.

Identification of a novel cis-acting negative regulatory element affecting expression of the CYP1A1 gene in rat epidermal cells.

Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene are toxic to rat epidermal cells in low passages (3 to 6), but cultures of high passage (>/=15) are resistant. Since such compounds can be metabolically activated by cytochrome P4501A1, we have examined the regulation of this gene in low and high passage cells. Consistent with this difference, little or no 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible P4501A1 mRNA or enzyme activity was observed in high passage as compared to low passage cultures.

Dioxinlike properties of a trichloroethylene combustion-generated aerosol.

Conventional chemical analyses of incineration by-products identify compounds of known toxicity but often fail to indicate the presence of other chemicals that may pose health risks. In a previous report, extracts from soot aerosols formed during incomplete combustion of trichloroethylene (TCE) and pyrolysis of plastics exhibited a dioxinlike response when subjected to a keratinocyte assay. To verify this dioxinlike effect, the complete extract, its polar and nonpolar fractions, some containing primarily halogenated aromatic hydrocarbons, were evaluated for toxicity using an embryo assay, for antiestrogenicity using primary liver cell cultures, and for the ability to transform the aryl hydrocarbon receptor into its DNA binding form using liver cytosol in a gel retardation assay.

Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals.

Exposure to specific polychlorinated diaromatic hydrocarbons (PCDH), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), produces a wide variety of species- and tissue-specific toxic and biological effects. Many of these responses are mediated by the Ah receptor (AhR) and are modulated by the interaction of the PCDH:AhR complex with its DNA recognition sequence (the dioxin-responsive element (DRE)). We have constructed a recombinant expression plasmid which contains the luciferase gene under TCDD-inducible control of several DREs and responds to TCDD-like chemicals with the induction of firefly luciferase.

Species-specific antagonism of Ah receptor action by 2,2',5,5'-tetrachloro- and 2,2',3,3'4,4'-hexachlorobiphenyl.

Using recombinant cell lines showing Ah receptor-controlled expression of a luciferase reporter gene, the interaction of di-ortho-substitute polychlorinated biphenyls (PCBs) with Ah receptor agonists was studied. In the recombinant Hepa1c1c7 mouse hepatoma (H1L1.1c7) cells strong antagonistic interaction of 2,2',5,5'-tetrachlorobiphenyl (PCB52) with luciferase expression induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3',4,4'-tetrachlorobiphenyl (PCB77) was observed, and similarly, between 2,2',3,3',4,4'-hexachlorobiphenyl (PCB128) and PCB77.

DNA binding of the transformed guinea pig hepatic Ah receptor complex: identification and partial characterization of two high-affinity DNA-binding forms.

We have examined and characterized the binding of transformed guinea pig hepatic Ah receptor to its specific DNA recognition site, the dioxin-responsive element (DRE), using gel retardation analysis. Saturation binding analysis of transformed TCDD:AhR complexes were indicative of a single high-affinity binding site (Kd = 2.5 +/- 0.

Protein kinase C is not involved in Ah receptor transformation and DNA binding.

Induction of cytochrome P4501A1 by 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) is mediated by the Ah receptor (AhR) complex, a ligand-dependent DNA-binding transactivator. Recently a role for protein kinase C (PKC) in the induction response has been reported in which PKC or a related kinase positively modulates AhR activity. We have examined the role of PKC by determining the effect of two nonspecific PKC inhibitors, H7 and staurosporine, and one specific PKC inhibitor, calphostin c, on AhR functionality.

Binding of transformed Ah receptor complex to a dioxin responsive transcriptional enhancer: evidence for two distinct heteromeric DNA-binding forms.

Guinea pig hepatic Ah receptor (AhR) complex was transformed in vitro to its DNA-binding form by incubation with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Transformed TCDD-AhR was covalently cross-linked by UV-irradiation to a bromodeoxyuridine-substituted oligonucleotide containing its specific DNA recognition site, the dioxin responsive element (DRE). Denaturing gel electrophoresis and autoradiography identified four TCDD-inducible protein-DNA complexes, with molecular masses of approximately 97, 105, and 115 kDa and a somewhat broader complex at 247 kDa.

TCDD causes stimulation of c-ras expression in the hepatic plasma membranes in vivo and in vitro.

A series of in vivo and in vitro experiments were conducted to determine the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) administered on the expression of c-ras. Differences in c-ras expression between control and TCDD treated groups were determined by immunoassay of p21ras protein, or indirectly measured by the specific binding of 3H-GTP to hepatic plasma membrane preparations. Intraperitoneal injection of sublethal doses of TCDD significantly elevated (P less than 0.

2,3,7,8-Tetrachlorodibenzo-p-dioxin causes increases in expression of c-erb-A and levels of protein-tyrosine kinases in selected tissues of responsive mouse strains.

2,3,7,8,-Tetrachlorodibenzo-p-dioxin (TCDD) administered in vivo causes drastic reduction in the weight of the mouse thymus at low doses (e.g., 30 micrograms/kg single i.

The relationship between labor and route of delivery in the preterm infant.

The purpose of this prospective study was to evaluate the effects of the active phase of labor and route of delivery on the frequency of germinal layer/intraventricular hemorrhage in 89 infants with ultrasound-estimated fetal weights less than or equal to 1750 gm. Twenty-eight infants (31.5%) had germinal layer/intraventricular hemorrhage within 1 hour after birth and an additional 15 infants (17%) had germinal layer/intraventricular hemorrhage beyond 1 hour after birth.