Blood levels of dehydroepiandrosterone sulfate (DHEA-S) and the risk of breast cancer

In North American women at low or high risk of developing breast cancer, as assessed by an epidemiologic questionnaire, the plasma concentration of dehydroepiandrosterone sulfate shows a statistically significant circannual variation. In adolescents, in all seasons, circulating dehydroepiandrosterone sulfate is a classifier of the risk of developing breast cancer, a relatively low concentration of this hormone being associated with an increased risk.     

Inhibition of the progesterone-dependent induction of meiosis by gammexane in Xenopus laevis oocytes.

Bundles of fibers of hemoglobin S in the presence of 2,3-diphosphoglycerate or inositol hexaphosphate have been prepared from stirred solutions and examined by electron microscopy. The bundles are found to contain ordered arrays of fibers in an eight-stranded form, with strands staggered by 37 Å, as characterized by optical and computer transforms. The characteristic reflections observed for individual fibers are also seen for large areas of the bundles, indicating the presence of the same form of the fibers throughout the bundles. Since 2,3-diphosphoglycerate is the natural hemoglobin cofactor, the structure observed in these studies is likely to bear a close correspondence to the structure $\text{in vivo}$.     

Similarities and differences of the binding of estradiol and 4-hydroxytamoxifen (an antiestrogen) in the chick oviduct cytosol

The binding characteristics of [³H]estradiol and 4-[³H]hydroxytamoxifen (a powerful estradiol antagonist) in the chick oviduct cytosol was analyzed by sucrose gradient centrifugation and dissociation kinetics experiments at 28°C. Heating the cytoplasmic estradiol-estrogen receptor complexes led to the ‘transformation’ of the receptor; as with the estrogen receptor in other target tissues and species, the transformed receptor sedimented in the 5 S region of sucrose gradients containing 0.4 M KCI and had a slower rate of dissociation of bound estradiol. Upon heating, the cytoplasmic 4-hydroxytamoxifen complexes also appeared to undergo similar changes in their physical states as analyzed by sedimentation rates and dissociation kinetics, and we conclude that antiestrogen can transform the receptor. Sodium molybdate inhibited the temperature mediated changes with both estrogen and antiestrogen complexes. Slight but consistent differences in the sedimentation coefficient and rate of ligand dissociation were observed between the complexes formed by estradiol and 4-hydroxytamoxifen but the relevance to opposite biological activities remains unknown.     

Affinity chromatography of the uterine estradiol receptor on estradiol-PAB-cellulose: an artefact.

Estradiol-PAB-cellulose, an easily prepared adsorbent, has been proposed to purify the uterine estradiol receptor according to the principle of biospecific affinity chromatography. It apparently removes all hormone binding sites when cytosol preparations are incubated with it. A systematic study of this adsorbent was undertaken, including the synthesis and testing of the radioactive material. Two main results were obtained: 1) Estradiol-PAB-cellulose is heavily contaminated with free ligand and releases it during the normal chromatographic conditions. 2) Estradiol spacer derivatives (hydroxyethylphenyl-diazo (2 or 4)-estradiol) have a very low affinity for the receptor (Ki = 10 muM). The conclusion is that estradiol-PAB-cellulose is unsuitable for affinity chromatography of estradiol receptor.     

Studies of testosterone-induced involution of the bursa of Fabricius

The present investigation deals with the effect of testosterone on each of the tissue components of the bursa of Fabricius: the endodermal epithelium, the mesenchyme, and the hemopoietic stem cells. Tissue combination experiments between testosterone-treated endoderm and normal mesenchyme and vice versa have shown that the androgen damages irreversibly the bursal epithelium. The latter is not seeded by hemopoietic stem cells and cannot undergo follicle formation when treated with high doses of testosterone. This occurs even if it is associated with a nontreated bursal mesenchyme. On the contrary, associations of testosterone-treated mesenchyme with normal endoderm result in normal bursa histogenesis. By using an original test of viability for lymphoid cells based on the application of the quail-chick marker system, we demonstrate that disappearance of hemopoietic cells in the endoderm results from their expulsion from the bursa and not from their death in situ. The conspicuous effect of testosterone on the bursa of Fabricius can be related to the levels of androgen receptors found in the organ. Typical cytosol androgen receptors are demonstrated in both bursal endoderm and mesoderm, although the amount in the former is higher. The concentration of binding sites in the bursa is >10 times higher than that in other organs such as lung and small intestine whose development is not affected by testosterone, contrasting with glucocorticosteroid receptor (measured by labeling with dexamethasone) found in the same concentration in all tissues.     

Are receptor-associated nuclear proteins associated with the earliest effects of steroid hormones?

The functional importance of the interaction of hsp90 with receptors for steroid hormones in the action of these hormones has been suggested. This hypothesis, although not yet proven, is supported by new data obtained in our laboratory and in those of others, whereas no conflicting experimental results have been presented. Our recent studies have dealt with the cloning of hsp90, transfection of normal and mutated receptors, the effects of the antihormone RU486 and immunohistochemistry.