Estrogen and progesterone receptors in gynecomastia.

The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy. The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

Migration of human and guinea pig airway epithelial cells in response to calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) is contained within and secreted by nerves and neuroepithelial bodies in the airway epithelium. To determine whether CGRP is a chemoattractant, tracheal epithelial cells isolated from 23 guinea pigs, and bronchial epithelial cells isolated from seven human donors were grown in primary culture for 4 to 5 days. Cell migration was assessed in a blindwell chemotaxis chamber. A gelatin-coated polycarbonate filter (8-microns pore size) separated the upper wells containing 5 x 10(4) cells from the lower wells containing chemoattractant (either CGRP or insulin). Cells were stimulated for 6 h, after which migrated cells on the filter were stained and counted. Both insulin and CGRP elicited migration of guinea pig tracheal epithelial (GPTE) cells. Exposure to 30 micrograms/ml insulin caused migration of 26.5 +/- 4.0 cells versus 4.3 +/- 0.6 cells per 10 hpf for control (P < 0.001). Treatment with 10(-9) M CGRP elicited migration of 39.6 +/- 2.5 cells versus 2.6 +/- 0.9 cells per 10 hpf for control (P < 0.001). Human bronchial epithelial (HBE) cells also migrated after stimulation with either insulin or CGRP: after 10(-9) M CGRP, HBE cell migration was 41.0 +/- 6.1 cells versus 3.4 +/- 0.3 cells per 10 hpf (P < 0.002; n = 3). Checkerboard analysis showed that the migration to CGRP was both chemotactic and chemokinetic. Incubation with 10(-8) M hCGRP-(8-37), a receptor antagonist for CGRP, plus 10(-9) M CGRP decreased GPTE cell migration to 9.8 +/- 2.4 cells versus 38.6 +/- 1.2 cells per 10 hpf for 10(-9) M CGRP alone (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen receptor binding affinity and uterotrophic activity of triphenylhaloethylenes.

Radiohalogenated estrogens have considerable potential for estrogen receptor-directed imaging and therapy for cancers which contain such receptors. In an effort to evaluate the potential of the triphenyl ethylene structure for such purposes we have synthesized 3 series of 2-halosubstituted triphenylethylenes containing oxygen functions in the 4 position of both aromatic rings attached to carbon 1 of the ethylene and tested their uterotrophic activity and competition for rat uterine low salt extractable, "cytosol" estrogen receptor. Most active, both as competitors for estradiol binding to estrogen receptors and by their ability to stimulate uterine growth are the 1,1-bis-4-hydroxyphenyl derivatives although the 1,1-bis-4-acetoxyphenyl derivatives also show good receptor affinity and demonstrate uterotrophic activities. However, since uterine cytosol contains enzymes which hydrolyze the acetates to the free phenols even during the incubation in the cold used for the competitive binding studies, a significant portion of the competition shown by the diacetates is probably due to their hydrolysis products, the free phenols. The 1,1-bis-4-methoxyphenyl derivatives are weak competitive binders and demonstrate uterotrophic activity only when administered at the higher, 20 micrograms, doses. Comparing the relative activities of various halogens at the 2 position, in each series the bromo and chloro derivatives generally were of similar activity and significantly more active than the corresponding iodo derivative. The non-halogen substituted derivatives were very good competitors for estrogen receptor binding but less active with regard to uterine growth stimulation, providing evidence that in vivo the vinyl halides would appear to be relatively stable to simple dehalogenation. Since they show reasonably good apparent affinities for the estrogen receptor and apparent in vivo stability, reflected by estrogenic activity, these halogen substituted triphenylethylene derivatives appear to be promising substrates for investigations of estrogen receptor directed imaging and therapy.