beta-endorphin and Fibrocystic-Breast-Disease

From preclimacteric women (n = 10, 45-50 years of age) with gross cystic breast disease, levels of beta-endorphin, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, cortisol and prolactin were assayed radiochemically in the breast cyst fluid and in plasma. The beta-endorphin concentration (fmol/ml) was increased more than fourfold in the breast cyst fluid (17.6 +/- 4.6 SEM) than in plasma (4.2 +/- 0.5 SEM). In the breast cyst fluid, estradiol was increased 41-fold (1738.2 +/- 350.5 SEM pg/ml), and progesterone 47-fold (65.47 +/- 8.25 SEM ng/ml) more than in plasma. The significantly increased values of beta-endorphin, estradiol and progesterone in the breast cyst fluid and the identification of beta-endorphin in cyst-lining epithelia demonstrate the local synthesis. Growth factor-like properties of beta-endorphin and estradiol are accountable for the propagation of cystic changes. The autonomic formation and function of beta-endorphin, estradiol and progesterone in cyst compartments can not be related with the levels of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and cortisol, which were significantly higher in plasma than in the breast cyst fluid. In the breast cyst fluid, prolactin could not detected to be significantly higher than in plasma. In addition the plasma-concentration of testosterone, androstenedione, thyroxin, triiodothyronine, thyroid-binding globulin, sexual-hormone-binding-globulin could be detected within the normal range. In this study we could demonstrate the synergism of beta-endorphin, steroid hormones and peptide hormones which advance the growth of gross cystic disease of preclimacteric women. Beta-endorphin was also examined by immunocytochemical assays (fluorescence, alkaline phosphatase and horseradish peroxidase method), in 11 women with pure fibrocystic disease, in 7 women with fibrocystic disease combined with a carcinoma in situ and in 15 women with fibrocystic disease combined with invasive carcinoma of the breast. Sections of frozen and paraffin embedded tissue of the same patient were reacted with anti-beta-endorphin antiserum. The immunoreactivity of beta-endorphin was intense in normal, proliferative altered and cyst-lining epithelia of fibrocystic disease and decreased in atypical epithelia and carcinoma cells of the breast. The degree of beta-endorphin staining is related to the degree of cell differentiation. In addition, nuclea

Topics: beta-Endorphin; Breast; Breast Neoplasms; Female; Fibrocystic Breast Disease; Hormones; Humans; Immunohistochemistry; Middle Aged; Receptors, Cell Surface; Steroids

Opioid peptides have a variety of pathophysiologic actions, playing a novel important role in human breast cancer. The expression of beta-endorphin was studied in 84 human breast cyst fluids from gross cystic breast disease-affected patients. The concentration of beta-endorphin in pooled breast cyst fluids was over four-fold higher than in respective plasma with a significant increase in the mean value of the 'metabolically active' apocrine cysts when compared with flattened cysts (P < 0.001). The higher levels of Type I cyst suggest de novo mammary synthesis of endogenous opioid peptides and could represent an altered expression of biosynthetic activity of apocrine breast cells, providing a possible explanation on functional changes of gross cysts, on the mechanism of their formation and a perspective relationship to breast cancer risk.

Topics: Adult; beta-Endorphin; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Radioimmunoassay

Circulating levels and cyst fluid concentrations of beta-endorphin (beta-EP), estradiol, progesterone, and prolactin were measured by radioimmunoassays in 10 premenopausal women with gross breast cysts. In addition, aspirates and frozen tissue sections from cystic lesions were investigated immunocytochemically for a possible beta-EP production. Epithelia of dilated ducts, smaller cysts, and hyperplastic lesions without atypia showed a strong positive reaction in the cytoplasm. In apocrine metaplasia, this staining was concentrated in the apical region. The staining intensity in atypical hyperplasia was diminished. Occasionally, normal duct and lobular epithelia exhibited positive beta-EP immunostaining. Levels of beta-EP, estradiol, and progesterone in the cyst fluid were significantly higher than in blood, but no significant differences were observed for prolactin. The ratios of progesterone to estradiol, estradiol to prolactin, and progesterone to prolactin in the cyst fluid were considerably higher than in blood. This suggests that beta-EP and steroid hormones are secreted from the lining epithelia into the breast cysts.

Topics: beta-Endorphin; Estradiol; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Progesterone; Prolactin; Radioimmunoassay

Breast cyst fluid (BCF) and plasma levels of beta-endorphin (beta-EP), oestradiol (E2), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), prolactin (PRL) and cortisol were assayed radiochemically in a group of 10 premenopausal women aged 45-50 years suffering from gross cystic breast disease. The concentration of beta-EP (fmol/ml) in BCF (17.6 +/- 4.6 S.E.) was over four times higher than that in plasma (4.2 +/- 0.5 S.E.). The level of E2 was 41 times higher (1738.2 +/- 350.5 S.E. pg/ml) and that of P was 47 times higher (65.47 +/- 8.25 S.E. ng/ml) in BCF than in plasma. The significantly increased values of beta-EP, E2 and P in BCF and the identification of beta-EP in the cyst-lining epithelium indicated that local synthesis occurs. Growth factor-like properties of beta-EP and E2 are responsible for the propagation of cystic changes. The autonomous formation and activity of beta-EP, E2 and P in cystic formations were not correlated with LH, FSH, TSH and cortisol levels, which were significantly higher in plasma than in BCF. The concentration of PRL in BCF was not significantly higher than that in plasma. Moreover, the plasma concentrations of testosterone, androstenedione, thyroxine, triiodothyronine, thyroxine-binding globulin and sex-hormone-binding globulin were within the normal ranges. In this study we demonstrated synergism between beta-EP and steroid hormones which encourages the development of gross cystic disease in premenopausal women.

Topics: beta-Endorphin; Estradiol; Exudates and Transudates; Female; Fibrocystic Breast Disease; Follicle Stimulating Hormone; Hormones; Humans; Hydrocortisone; Luteinizing Hormone; Middle Aged; Progesterone; Prolactin; Thyrotropin

Histochemical and immunohistochemical methods were used to examine 29 malignant tumors (18 lobular and 11 invasive carcinomas) and 34 fibroadenomas of the mammary gland (MG). APUD cells containing serotonin, melatonin, and beta-endorphine were shown to be present in the duct epithelium of the normal MG and its pericanalicular fibroadenoma. APUD cells were detected in 21 of the 29 malignant tumours of MG. Hormonal differences of APUD cells were found in poorly and well differentiated carcinomas: the former contained serotonin, melatonin, and beta-endorphine (inhibitors of proliferation), the latter--insulin and adrenocorticotropic hormone (stimulators of cell division). Such differences in the endocrine function of MG malignant tumors are likely to be significant in the clinical course and determination of prognosis for carcinomas of various differentiation.

Topics: Adenofibroma; Adrenocorticotropic Hormone; APUD Cells; beta-Endorphin; Breast Neoplasms; Carcinoma; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Melatonin; Serotonin