estrone-sulfate and estriol-3-sulfate

Topics: 17-alpha-Hydroxypregnenolone; Amniotic Fluid; Androsterone; Chromatography, Liquid; Dehydroepiandrosterone; Epitestosterone; Estriol; Estrone; Female; Gestational Age; Humans; Male; Pregnancy; Pregnancy Trimester, Second; Pregnenolone; Steroids; Tandem Mass Spectrometry

Human breast cyst fluid (BCF) contains an esterase that on the basis of electrophoretic mobility and response to inhibitors differs from those found in the plasma. From a total of 384 BCF samples analyzed for esterase using p-nitrophenyl hexanoate as substrate, 149 (39%) showed significant activity. The samples had been analyzed for the concentrations of the sulfates of estrone, estriol, dehydroepiandrosterone, as well as the potassium and sodium cations (K+/Na+). The data were submitted to statistical analysis using the Spearman rank order test. The esterase-positive samples exhibited a significant positive association with each of the steroid sulfates and the K+/Na+ ratios. Except for protein concentration, there was no significant correlation between the esterase-positive and esterase-negative cysts. These observations may have physiological significance in that high K+/Na+ ratio cysts have been related to the histological status of the cyst.

Topics: Biomarkers; Body Fluids; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Esterases; Estriol; Estrogens, Conjugated (USP); Estrone; Female; Fibrocystic Breast Disease; Humans; Potassium; Sodium; Steroids; Sulfates

Estriol-3-sulfate (E3S) is present in human breast cyst fluid (BCF) in median levels of 8.7-10.4 nmol/L, yet is barely detectable in the serum (less than 0.034 nmol/L). The source of this huge concentration of E3S is unknown. It may accumulate from blood by active transport or be synthesized and concentrated within the cyst. Since estrone sulfate (E1S) and its possible precursor, dehydroepiandrosterone sulfate (DHEAS) are elevated in BCF, E3S may originate via 16 alpha-hydroxylation of E1S. The present study examined the correlations between the levels of DHEAS and E1S with those of E3S in BCF. The sodium and potassium ions were also quantified and related to the steroid concentrations. By linear regression analysis of log-normalized data there was a highly significant correlation between the concentrations of E1S and E3S (n = 355, r = 0.690, P less than 0.001) and between DHEAS and E3S (n = 361, r = 0.577, P less than 0.001). The BCF were classified according to their K/Na ion ratios: type 1, greater than 1.0, type II, less than 0.25, and type III, 0.25-1.0. By Student's t test, the concentrations of E3S differed between each BCF Type (P less than 0.002). This was also true for E1S and DHEAS. Type 1 cysts were associated with the highest estrogen sulfate levels and type II with the lowest levels. The possible physiological importance of this observation resides in reports that the BCF type expressing the highest steroid concentrations has been related to an aporcine-like epithelial lining of the cyst wall and a somewhat higher risk for developing breast cancer. The results suggest that E3S in BCF may originate from E1S, but alternate mechanisms are not precluded.

Topics: Aryl Hydrocarbon Hydroxylases; Body Fluids; Breast Diseases; Cysts; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estriol; Estrone; Humans; Osmolar Concentration; Potassium; Regression Analysis; Sodium; Steroid 16-alpha-Hydroxylase

Gross cystic disease (GCD) of the breast imparts a minimal risk for the development of breast cancer. Relative to serum, breast cyst fluid (BCF) in patients with GCD is highly concentrated in androgens, estrogens, certain enzymes, and bioactive polypeptides. In addition, the cations, sodium and potassium, vary markedly and inversely in BCF. We have focused on the levels of estriol-3-sulfate (E3S), which are several orders of magnitude greater in BCF than in blood. In this preliminary study, about 55 specimens of BCF were analyzed for E3S, its possible precursors, estrone sulfate (E1S) and dehydroisoandrosterone sulfate (DHAS), and the cations, sodium and potassium. The data were analyzed statistically by linear regression analysis. E3S correlated directly with both E1S and DHAS (p less than 0.002), and inversely with the Na/K ratio (p less than 0.003). Low Na/K ratio has been associated with secretory processes in cyst epithelium. The data suggest that E3S may originate via 16 alpha-hydroxylation of estrogen in the cyst and that elevated E3S levels may be indicative of a secretory epithelium. This is part of an ongoing prospective study involving 400 subjects with GCD to see whether hormonal and enzymic profiles can be related to cancer risk.

Topics: Aryl Hydrocarbon Hydroxylases; Bile Acids and Salts; Biopsy, Needle; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estriol; Estrone; Exudates and Transudates; Female; Fibrocystic Breast Disease; Humans; Potassium; Sodium; Steroid 16-alpha-Hydroxylase; Steroids

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]-Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.

Topics: Breast Neoplasms; Estradiol; Estriol; Estrone; Female; Humans; Menstruation; Polyunsaturated Alkamides; Progesterone; Receptors, Progesterone; Tamoxifen; Tumor Cells, Cultured