ABSTRACT
Plasma dehydroenpiandrosterone sulfate (DS), androstenedione (A2), estrone plus estradiol (E1+2) and estriol (E3) were measured in women treated with conjugated estrogens and controls. Plasma DS, A2, and E1+2 levels were higher in the premenopausal controls than in the untreated postmenopausal women; E3 levels were below the sensitivity of the assay. Estrogen conjugates, 1.25 mg or 2.5 mg daily, increased plasma E1+2 to levels similar to those in premenopausal untreated women, and E3 became readily assayable. A 0.625-mg dose increased the level of E3 without affecting E1+2; consequently, the plasma E3/E1+2 ratio was elevated. It is concluded that at the lowest dose 16 alpha-hydroxylase activity, perhaps by substrate induction, is sufficient for the exogenous esogenous estrogens to be largely metabolized to E3. Estrogen conjugates had no detectable effect on plasma DS or A2.
Subject(s)
Estrogens, Conjugated (USP)/pharmacology , Gonadal Steroid Hormones/blood , Androstenedione/blood , Dehydroepiandrosterone/blood , Estradiol/blood , Estriol/blood , Estrone/blood , Female , Humans , Menopause , Steroid 16-alpha-HydroxylaseABSTRACT
A simple method for the assay of specific progesterone receptors in breast cancer tissue is described. Progesterone receptors were detected in 63 of 74 breast cancer specimens (85%). Estrogen receptor positive tumors had a wide range of progesterone receptor concentrations, but in 77% of cases the level was above 3 fmol/mg protein. The progesterone receptor level was generally low in tumors lacking estrogen receptors, 75% of the samples having concentrations between 0 and 3 fmol/mg protein. Unlike estrogen receptors, age had no influence on the number of progesterone receptors in breast cancer tissue.
Subject(s)
Breast Neoplasms/metabolism , Adult , Aged , Cell Nucleus/metabolism , Cytoplasm/metabolism , Female , Humans , Hydrocortisone/pharmacology , Middle Aged , Norethindrone/metabolism , Progesterone/metabolism , Protein Binding , Transcortin/metabolismABSTRACT
Specific cytoplasmic androgen and estrogen binding has been measured in human benign prostatic hypertrophy and carcinomatous tissue. In vitro support for the binding of estramustine phosphate (Estracyt) to both estradiol- and dihydrotestosterone-binding sites is presented, which in part could explain the clinical effect of estramustine phosphate when pure estrogenic compunds are not effective.
Subject(s)
Androgens/metabolism , Estradiol/metabolism , Estramustine/pharmacology , Nitrogen Mustard Compounds/pharmacology , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/metabolism , Binding Sites , Cytoplasm/metabolism , Estramustine/metabolism , Estrogens/metabolism , Humans , MaleABSTRACT
A simple procedure for the assay of specific estrogen receptors in breast cancer tissue is described. Estrogen receptors were detected in 74% of primary tumors, 71% of skin metastases and 63% of lymph node metastases. Postmenopausal patients and younger oophorectomized women had estrogen receptor-containing tumors more frequently, and at higher levels, than uncastrated, premenopausal, patients. The stability of estrogen receptors was not affected by the transportation of samples from distant hospitals, providing that they were kept frozen in Tris buffer, pH 8.0, at all times.
Subject(s)
Breast Neoplasms/metabolism , Estrogens/metabolism , Receptors, Cell Surface , Adult , Age Factors , Aged , Castration , Estradiol/metabolism , Female , Humans , Hydrogen-Ion Concentration , Lymphatic Metastasis , Mastectomy , Menopause , Middle Aged , Neoplasm Metastasis , Skin Neoplasms/metabolism , Specimen Handling , TemperatureABSTRACT
The urinary excretion of corticosteroid sulfates and free cortisol were determined in 150 breast cancer patients. Four of 60 cases of early breast cancer (7%) and 26 of 90 patients with advanced breast cancer (29%) showed an elevated urinary corticosteroid sulfate excretion. Urinary free cortisol was usually normal. Estrogen receptor assays were performed on tumor samples from 67 breast cancer patients; 24 were from primary lesions obtained at mastectomy, 3 from inoperable primaries in patients with systemic metastases, and 40 from metastases. Sixteen of the primary breast cancers (67%), 26 of the metastases (65%) and 1 of the 3 inoperable primaries contained estrogen receptors. With 2 exceptions, patients with an increased urinary corticosteroid sulfate excretion also had estrogen receptor-containing tumors.
Subject(s)
Adrenal Cortex Hormones/urine , Breast Neoplasms/metabolism , Estrogens/metabolism , Receptors, Cell Surface , Adult , Aged , Bone Neoplasms , Female , Humans , Hydrocortisone/urine , Middle Aged , Neoplasm Metastasis , NeoplasmsABSTRACT
Urinary excretions of free cortisol and corticosteroid sulfates were determined in 31 female controls, 77 breast cancer patients, 14 cases of colonic cancer, and 7 patients with bronchial carcinoma. Elevated corticosteroid sulfate excretion was present in 38% of patients with locally recurrent breast cancer and 30% of those with distant metastases, but in only 13% of the "early" breast cancer cases. A similar abnormality was seen in colonic cancer. Urinary free cortisol was usually normal. ACTH stimulation in a normal subject produced marked increases of both urinary free cortisol and corticosteroid sulfates. It is concluded that elevated corticosteroid sulfate excretion in cancer patients arises from an increased cortisol production rate combined with increased sulfurylation of the steroid. In bronchial carcinoma patients, changes similar to those occurring in the ACTH-treated normal subject may have resulted from ectopic ACTH production in the tumor.
