A role for acetylcholine receptors in their own aggregation on muscle cells.

Both neurotrophic factors and activity regulate synaptogenesis. At neuromuscular synapses, the neural factor agrin released from motor neuron terminals stimulates postsynaptic specialization by way of the muscle specific kinase MuSK. In addition, activity through acetylcholine receptors (AChRs) has been implicated in the stabilization of pre- and postsynaptic contacts on muscle at various stages of development.

L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle.

Agrin activation of muscle specific kinase (MuSK) initiates postsynaptic development on skeletal muscle that includes the aggregation of acetylcholine receptors (AChRs; Glass et al. [1996]: Cell 85: 513-523; Gautam et al. [1996]: Cell 85: 525-535).

Sex differences in cocaine- and nicotine-induced antinociception in the rat.

Several recent reports describe sex differences in opioid antinociception. The present study examined sex differences in stimulant-induced antinociception. On the 50 degreesC hotplate test, cocaine (0.

Binding of the glucocorticoid receptor complex to the nucleosomal core in the P1798 mouse lymphosarcoma.

Binding of the glucocorticoid receptor complex to nucleosomes has been studied using the mouse P1798 lymphosarcoma. Cells were incubated with [3H]triamcinolone acetonide (TA), and nuclei prepared and digested with 3 different concentrations of micrococcal nuclease. After fractionation with EDTA and NaCl, it was observed that [3H]TA bound with similar specific radioactivity to mononucleosomes containing both core and linker DNA, of 183 +/- 5, and 168 +/- 4 base pair lengths, respectively, as well as to core size DNA, of 148 +/- 3 base pair length, suggesting that the glucocorticoid receptor bound to the core portion of the nucleosome.

Effect of a high-protein-low-carbohydrate diet on toxicity and antitumor activity of 5-fluorouracil in mice.

The effect of different levels of dietary protein on 5-fluorouracil (FUra) toxicity and antitumor activity was assessed in female (BALB/c X DBA/2Ha)F1 (CDF1) and BALB/c mice bearing the P1798 lymphosarcoma. In the toxicity experiments, CDF1 mice were fed diets containing 5% [low protein (LP)], 20% [normal protein (NP)], or 60% [high protein (HP)] casein for 22 days and were then given a single ip injection of 275 mg FUra/kg. As determined by effects on the white blood cell count and by changes in body weight, FUra was least toxic in mice fed the HP diet.

Effect of the prostaglandin synthetase inhibitor indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat.

The effect of the prostaglandin synthetase inhibitor indomethacin on the dietary fat enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis has been examined in female Sprague-Dawley rats. Rats were fed either a normal-fat or high-fat diet (5 or 18% corn oil, respectively) with or without 0.004% indomethacin, starting 3 days after a single intragastric intubation of 5 mg 7,12-dimethylbenz(a)anthracene.

Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat.

The effect of androgen on the levels of the cytosol progesterone receptor was examined in the transplantable rat mammary tumor MT-W9B and in the normal uteri of inbred WF rats. Progesterone receptor levels were barely detectable in tumors grown in male WF rats but were increased after castration or administration of 17 beta-estradiol. Both effects were blocked by testosterone.

Glucocorticoid receptors and the effect of glucocorticoids on the growth of B16 melanoma.

The glucocorticoid receptors were measured and characterized in the transplantable B16 murine melanoma using [3H]-dexamethasone by a charcoal adsorption technique. In the tumor cytosols assayed, the levels of receptors ranged from 44 to 200 fmol/mg protein, and the corresponding Kd's ranged from 2 to 43 nM. Sucrose density gradient analysis showed a peak sedimenting at 7.

Dichotomous effects of tamoxifen on a transplantable rat mammary tumor.

The effect of the antiestrogen tamoxifen on growth of the transplantable autonomous mammary tumor MTW-9B was compared with its effects on progesterone and estrogen receptor levels. Growth of the tumor was similar in intact rats, ovariectomized rats, or ovariectomized rats given estradiol, in both the presence and the absence of tamoxifen. Progesterone receptor levels, however, were reduced by ovariectomy and restored by estrogen administration.

High incidence and characterization of glucocorticoid receptors in human malignant melanoma.

The glucocorticoid receptor was characterized in biopsy samples from patients with recurrent malignant melanoma. Glucocorticoid receptors were measured by the charcoal-adsorption technique. Tumor cytosol from approximately 86% (25/29) of the patients contained large quantities of receptors (20-324 fmol/mg protein).

Functionality of estrogen receptor and tamoxifen treatment of R3327 Dunning rat prostate adenocarcinoma.

The functionality of the estrogen receptor as determined by the effect of estrogen on progesterone receptor levels and the effect of tamoxifen on tumor growth has been examined in the R3327 Dunning rat prostate adenocarcinoma. The progesterone receptor was absent in 78% of prostate tumors grown in male Copenhagen X Fischer F1 rats but was induced in tumors taken from rats given injections of 25 microgram estradiol benzoate per kg for 10 days. This result suggested that the tumor might be sensitive to the antiestrogen tamoxifen, and it was subsequently shown that treatment of rats with tamoxifen (0.

Antiglucocorticoids: in vivo assay and evaluation of cortexolone, progesterone, and 6-beta-bromoprogesterone.

In vitro antiglucocorticoids (cortexolone and progesterone) were evaluated as in vivo antagonists of dexamethasone-induced increases in liver tyrosine amino transferase (TAT; EC 2.6.1.

Mammary cancer: selective action of the estrogen receptor complex.

Progesterone receptors in the autonomous rat mammary tumor MTW-9B are reduced 80 to 90 percent after ovariectomy, but are not reduced if ovariectomized animals are given estrogen. Tumor growth, however, is independent of estrogen status and insensitive to pharmacological doses of estradiol. This represents an unusual system characterized by a selective action of an inducing agent on the genome.

Sex differences in the concentrations of glucocorticoid receptors in rat liver and thymus.

The effects in rats of adrenalectomy, hypophysectomy, ovariectomy or combinations of these operations on the concentrations of glucocorticoid receptors in the cytosol of liver and thymus were measured. The concentrations of glucocorticoid receptors were lower in cytosols from liver and thymus of female than of male rats. After adrenalectomy, there was a significant increase in the concentrations of receptors measured in the cytoplasm from the liver and thymus of female rats and from the liver of male rats.

Nuclear binding of steroid-receptor complex to lymphosarcoma P1798 resistant and sensitive cells and effect of concanavalin A on receptor levels.

Glucocorticoid-resistant P1798 cell lines have been found to contain levels of glucocorticoid receptor comparable to receptor levels in glucocorticoid-sensitive P1798 cells. Previously, most of the P1798 resistant cells examined were found to contain low levels of glucocorticoid receptor, and this was thought to account for the resistance of these cells to glucocorticoid treatment. Resistant cells with high receptor levels exhibited 10 to 50 percent lower levels of nuclear binding than did sensitive cells.

Glucocorticoid receptors in Morris hepatomas and host liver and the correlation of biological activity with receptor levels.

Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constants (Ka), sedimentation coefficients, and sensitivity to sulfhydryl-blocking reagents were found to be similar when hepatoma receptors were compared with the known properties of the liver receptor.

Glucocorticoid activity of various progesterone analogs: correlation between specific binding in thymus and liver and biologic activity.

When tested in an in vitro assay system, progesterone and various analogs of this steroid were shown to compete with [3H] triamcinolone acetonide (TA) for specific glucocorticoid receptors in both rat liver and thymus. Of these analogs, the following derivatives of progesterone were potent competitors of TA binding and, when injected into adrenalectomized rats, induced regression of the thymus and marked increases in hepatic tyrosine aminotransferase activity: 11 beta-hydroxyl, 6 alpha-methyl, 6 alpha, 16 alpha-dimethyl, and 6 alpha-methyl-17 alpha-hydroxyl. In contrast, progesterone, 16 alpha-methyl, and 17 alpha-hydroxy progesterone competed with TA in vitro but failed to elicit either gluco- or antiglucocorticoid activity in vivo.

Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding.

The mechanism of action of glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free amino acid content, activity of amino acid-metabolizing enzymes, and binding to cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and body weight occurred following administration of cortisol, triamcinolone diacetate, and triamcinolone acetonide to adrenalectomized rats. Treatment with triamcinolone diacetate also reduced the level of several free amino acids and enhanced the activity of a myofibrillar protease in skeletal muscle.