ABSTRACT
1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31%) and 5/9 (56%) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44% vs 23%). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63%) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54% vs 38% in rectum and 78% vs 56% in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated.
Subject(s)
Colorectal Neoplasms/chemistry , Receptors, Steroid/analysis , Adult , Aged , Brazil , Female , Humans , Male , Middle Aged , Receptors, Androgen/analysis , Receptors, Estrogen/analysis , Receptors, Glucocorticoid/analysis , Receptors, Progesterone/analysisABSTRACT
1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31 per cent ) and 5/9 (56 per cent ) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44 per cent vs 23 per cent ). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63 per cent ) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54 per cent vs 38 per cent in rectum and 78 per cent vs 56 per cent in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Colorectal Neoplasms/chemistry , Receptors, Steroid/analysis , Brazil , Receptors, Androgen , Receptors, Estrogen , Receptors, Glucocorticoid/analysis , Receptors, Progesterone/analysisABSTRACT
The effects of estradiol (E2), dihydrotestosterone (DHT) and dehydro-3-epiandrosterone (DHEA) on proliferation and progesterone receptor induction were studied in a breast cancer cell line (T47D) expressing estrogen, androgen, and progesterone receptors. A significant enhancement of growth and progesterone receptor expression was observed after treatment with E2 and DHEA, which was antagonized by the antiestrogen tamoxifen and not altered by the antiandrogen flutamide, supporting the involvement of estrogen receptors. When cells were treated with either E2 or DHEA, transforming growth factor-alpha mRNA was induced. DHT treatment did not alter growth but was effective in stimulating androgen receptors and down-regulating progesterone receptors.
Subject(s)
Androgens/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Receptors, Estrogen/metabolism , Receptors, Progesterone/drug effects , Breast Neoplasms/chemistry , Cell Division/drug effects , Dehydroepiandrosterone/pharmacology , Dihydrotestosterone/pharmacology , Down-Regulation , Estradiol/pharmacology , Female , Flutamide/pharmacology , Humans , RNA, Messenger/analysis , Receptors, Androgen/drug effects , Receptors, Estrogen/drug effects , Receptors, Progesterone/biosynthesis , Tamoxifen/pharmacology , Transforming Growth Factor alpha/biosynthesis , Tumor Cells, CulturedABSTRACT
Characteristics of beta-adrenoceptors were analyzed using radioligand-binding techniques with 3H-dihydroalprenolol in lung specimens from 11 children with pulmonary hypertension (median age, three years) undergoing surgical repair of congenital heart defects and four pediatric control subjects (median age, five years) undergoing thoracotomy for removal of neoplasms or cysts. Scatchard analysis of 3H-DHA binding to lung membranes showed similar values of the dissociation constant in both groups (Kd = 0.72 +/- 0.22 nM in patients vs 1.22 +/- 0.22 nM in controls; p = NS). The receptor density was significantly increased in patients in comparison with controls, with respective values of 164 +/- 19 and 95 +/- 13 fmol/mg of protein (p less than 0.025), and correlated directly with mean pulmonary arterial pressure (r = 0.82; p less than 0.0005). No significant relationship was observed between receptor number and pulmonary arterial medial thickness. Thus, the increase in receptor density in these patients may be related to adaptative changes in cells other than vascular smooth muscle.
Subject(s)
Heart Defects, Congenital/complications , Hypertension, Pulmonary/metabolism , Lung/metabolism , Receptors, Adrenergic, beta/metabolism , Adolescent , Biopsy , Blood Pressure/physiology , Bronchial Arteries/metabolism , Bronchial Arteries/pathology , Child , Child, Preschool , Dihydroalprenolol/metabolism , Humans , Hypertension, Pulmonary/pathology , Hypertension, Pulmonary/physiopathology , Infant , Lung/blood supply , Lung/pathology , Receptors, Adrenergic, beta/isolation & purification , Species Specificity , TritiumABSTRACT
Using a saturation analysis over a wide range of [3H]estradiol at two temperatures 4 and 22 degrees C we have determined unoccupied (4 degrees C) and total (22 degrees C) type II estrogen binding site (EBS) levels in individual cytosols of 100 patients with breast cancer (50 post and 50 premenopausal). Exchange was found to be complete after 18 h at 22 degrees C and receptor degradation was negligible during this treatment. Steroid specificity and affinity determined by Scatchard and Rosenthal plot analysis were not altered at 22 degrees C. Carcinomas presented a higher total type II REBS level as compared unfilled type II binding sites or the classical ER, independently of menopausal status, phase of the menstrual cycle or positivity of ER. On the other hand, unoccupied type II EBS level was strongly correlated to the concentration of type I ER, being higher on the post-menopausal group and older patients.