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There are at least two classes of intracellular receptors for adrenocorticosteroid hormones in brain. Type I receptors have a high affinity for the naturally occurring gluco- and mineralocorticoids, corticosterone (CORT) and aldosterone (ALDO), respectively, and a very low affinity for synthetic glucocorticoids such as dexamethasone (DEX). type II receptors have a high affinity for the synthetic glucocorticoids, a lower affinity for CORT and a very low affinity for ALDO. In recent studies with mouse brain cytosol we have found a number of other biochemical differences between these two receptor types. In the present study, brain cytosol from adrenalectomized mice was prepared in HEPES buffer and subjected to various potentially inactivating treatments prior to assessment of Type I and Type II receptor specific binding capacity by incubation for 24 h at 0 degrees C with [3H]ALDO +/- [1H]RU 26988 (to prevent or permit the cross-binding of [3H]ALDO to Type II receptors) or [3H]DEX +/- [1H]Prorenone (to prevent or permit the cross-binding of [3H]DEX to Type I receptors), respectively. These studies revealed that 10-20% of the high-affinity (Kd = 3 nM) [3H]DEX specific binding capacity remained even after extensive, high concentration and repeated pretreatments with dextran-coated charcoal (DDC. to remove endogenous sulfhydryl-reducing reagents and other biochemicals). These procedures had little effect on Type I receptors. Further analyses revealed that DCC-resistant [3H]DEX binders were not Type I receptors since they were not saturated by [1H]Prorenone. These binders were also not inactivated by aging steroid-free cytosol at 0 degree C or by treating it with buffers containing 0.3 M KCl. Since these

It has been shown previously that Escherichia coli accumulates endogenously synthesized trehalose under osmotic stress. We report here that E. coli contained an osmotically regulated trehalose-phosphate synthase which utilized UDP-glucose and glucose 6-phosphate as substrates. In the wild type, the synthase was induced by growth in glucose-mineral medium of elevated osmotic strength and the synthase itself was strongly stimulated by K+ and other monovalent cations. A laboratory strain which expressed the synthase at a high constitutive level was found. GalU mutants, defective in synthesis of UDP-glucose, did not accumulate trehalose. Two genes governing the synthase were identified and named otsA and otsB (osmoregulatory trehalose synthesis). They mapped near 42 min in the flbB-uvrC region. Mutants with an otsA-lacZ or otsB-lacZ operon fusion displayed osmotically inducible beta-galactosidase activity; i.e., the activity was increased fivefold by growth in medium of elevated osmotic strength. Mutants unable to synthesize trehalose (galU, otsA, and otsB) were osmotically sensitive in glucose-mineral medium. But an osmotically tolerant phenotype was restored in the presence of glycine betaine, which also partially repressed the synthesis of synthase in the wild type and of beta-galactosidase in ots-lacZ fusion mutants.

To assay progesterone receptor (PR), we compared Abbott's enzyme immunoassay (PR-EIA) with a ligand-binding assay involving dextran-coated charcoal (PR-DCC), using cytosols prepared from 109 breast-cancer biopsies. Results by the two PR methods agreed well. Least-squares analysis produced a line of best fit having a slope of 0.88, an intercept on the PR-EIA axis of 16 fmol per milligram of protein, and a correlation coefficient (r2) of 0.87. To evaluate whether accurate PR-EIA measurements could be obtained on stored cytosols, we compared PR-EIA values for fresh cytosols with values for cytosols stored for various lengths of time up to 13 weeks. Agreement was excellent, especially when the samples showing very high binding (greater than 600 fmol per milligram of protein) were excluded. The lines of best fit after least-squares analyses of the remaining values had slopes between 1.0 and 1.1, intercepts less than 3 fmol/mg, and r2 all greater than 0.91.

Androgen receptor content was correlated with various prognostic factors in 274 patients with breast cancer. Receptor content was determined by the dextran-coated charcoal method (DCC). No direct relationship was found between androgen receptor content and age of patient, menstruation status, TN status and number of affected lymph nodes. But in 232 patients in whom tumour differentiation could be determined, there was a highly significant relationship between it and androgen receptor content (P less than 0.01). Similar correlations were found also between these prognostic factors and oestrogen or progesterone receptors. The percentage distribution of tumours of different degrees of differentiation was independent of the kind of demonstrable steroid-hormone receptor. However, the frequency of highly differentiated tumours rose with the number of different receptors that were determined. Thus steroid-hormone receptors can be considered as markers for differentiation. It seems possible that the additional determination of androgen receptors allows for a more exact selection of patients who should receive hormonal treatment.

The pathophysiology of the myopathy in dysthyroid states is poorly understood. We therefore tested the effects of thyroid hormones on muscle bioenergetics in humans and rats, using in vivo 31P NMR. Two hypothyroid patients had: low phosphocreatine to inorganic phosphate ratio (PCr/Pi) at rest, increased PCr depletion during exercise and delayed postexercise recovery of PCr/Pi. Eight thyroidectomized rats did not show abnormalities at rest, but muscle work induced by nerve stimulation resulted in a significantly (P less than 0.0001) lower PCr/Pi (35-45% of control) at each of the three stimulation frequencies tested (0.25, 0.5, and 1.0 Hz). Recovery rate was markedly slowed to one-third of normal values. Thyroxine therapy reversed these abnormalities in both human and rat muscle. Five patients and six rats with hyperthyroidism did not differ from normal controls during rest and exercise but had an unusually rapid recovery after exercise. The bioenergetic abnormalities in hypothyroid muscle suggest the existence of a hormone-dependent, reversible mitochondrial impairment in this disorder. The exercise intolerance and fatigue experienced in hypothyroid muscle may be due to such a bioenergetic impairment. The changes in energy metabolism in hyperthyroid muscle probably do not cause the muscular disease in this disorder.