The role oftissue interaction in the development of hormone responsiveness was studied in the embryonic mammary gland of the mouse, which becomes sensitive to testosterone on day 14. Previously, the mesenchyme had been identified as the sole target tissue for the hormone, although it-was also demonstrated that its response to testosterone required the presence of mammary epithelium. Using autoradiography, we now show that[3H]testosterone or [3H]5a-dihydrotestosterone is bound only by those mesenchymalcells closest to the epithelial mammary bud. When mammary epithelia were experimentally associated with mesenchyme of the mammary region and cultured together for 3 days in vitro, they also became surrounded by several layers of [3H]testosterone-binding mesenchymal cells. Correspondingly, this tissue association was accompanied by a substantial increase of androgen-binding sites in the explants. No hormone-binding mesenchymal cells were seen in combinations with epidermis or pancreas epithelium; only salivary epithelium showed a weak positive effect. From these results we conclude that mammary epithelium induces the formation of androgen receptors in adjacent mesenchyme and thereby controls the development of androgen responsiveness in this tissue.

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Our results suggest that migraineurs with aura differ from migraineurs without aura and healthy control subjects in terms of anxiety and depression. With regard to health-related locus of control, there was no correlation among mean number of migraine attacks per year, duration of disease, time of last migraine attack, and number of aura symptoms.

Utilizing (3H) cyclosporin C (3H CS-C), a dihydroderivative of cyclosporin A (CS-A), an assay for cyclosporin receptors on human peripheral blood lymphocytes was developed. The specific binding of (3H) CS-C was saturable, time-dependent, and reversible. A Kd of 1.2 x 10(-7) M and a maximum binding capacity (Bmax) of 7 pmol/10(6) cells was calculated from equilibrium binding studies. A Scatchard analysis confirmed a single population of high affinity binding sites and about 7 x 10(5) sites/cell. Kinetic analysis of specific binding at 37 degrees C yielded a pseudo-first order rate association constant of 1.1 x 10(6) M-1 min-1 and a zero order dissociation rate constant of 0.19 min-1. The Kd 1.7 x 10(-7) M calculated from kinetic studies agreed well with the value of 1.2 x 10(-7) M determined in equilibrium binding studies. Regarding the specificity of binding, (3H) CS-C binding to lymphocytes was inhibited with CS-A and CS-C; however, no inhibition with the biologically inert keto-CS-A was observed. Mitogens and various growth factors did not compete for the binding site when added simultaneously with the radiolabel. However, pretreatment with T cell mitogens such as PHA, Con A, or the OKT3 antibody reduced (3H) CS-C binding significantly. These results suggest that the binding site for CS-A is closely associated with the mitogenic receptor on lymphocytes.