Biomedical subjects

L Tseng

Publications and source records attributed to L Tseng.

At least 55 records · Page 3Linked to original sources

PubMed1988

The effect of progestin on rabbit endometrial aromatase activity.

The ability of rabbit endometrium to synthesize estrogen was investigated. Aromatase activity was measured by incubating the viable tissue fragments with [3H] testosterone at 37 degrees C and quantitated the [3H]estrogens at the end of 6 h incubation. The activity was not detectable in endometrium and myometrium of non-pregnant rabbits. In pregnant rabbit, the activity increased from 2 to 12 fmol/h/g of tissue in endometrium obtained from both gravid and nongravid uterine horns 4-8 days after mating. Aromatase activity in endometrium at implanted sites on the 8th day after mating reached up to 550 fmol/h/g of tissue. Hormonal regulation of the aromatase activity was studied directly in cultured rabbit endometrial stromal cells. Both progesterone and medroxyprogesterone acetate stimulated the activity with 2- to 25-fold increase over the control values (0.2-1 fmol/h/mg protein). The stimulation of aromatase activity by progestin was found to be both time- and dose-dependent. Estrogen, Bu2cAMP, forskolin, HCG or relaxin had no effect on the activity. Aromatase activity in glandular epithelial cells was neither detectable nor affected by progestin. These results indicate that aromatase activity in rabbit endometrium is concentrated in stromal cells and progestin stimulates the activity. However, estrogen, forskolin and relaxin which enhanced the stimulation of the activity by progestin in human endometrium had no effect on aromatase in rabbit endometrium. The increase of aromatase activity observed after the onset of conception may be physiologically important to increase the local estrogen content for decidualization of the endometrium.

Animals↗

PubMed1988

The effect of relaxin on cyclic adenosine 3',5'-monophosphate concentrations in human endometrial glandular epithelial cells.

The effects of relaxin (RLX), forskolin (Fk), and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro, a phophodeisterase inhibitor) on the accumulation of cyclic adenosine 3',5'-monophosphate (cAMP) in human endometrial glandular epithelial cells were studied. Epithelial glands were isolated from the endometrium by digesting the viable tissue fragments with collagenase. The epithelial glands were incubated with Ro, RLX, and Fk separately or in combination. The amount of cAMP was determined at the end of incubation. A moderate increase in cAMP content was observed in epithelial glands incubated with Ro alone. Accumulation of cAMP after incubation with RLX was observed only in the presence of Ro. Increase of cAMP content in response to RLX and Ro was time- and dose-dependent. The accumulation of cAMP was apparent in 5 min, reached the maximum after 15 min, and remained elevated for 17 h incubation. One nanogram per millileter RLX was effective to increase the cAMP content, with a maximal response at 100 ng/ml. The effect of Ro and the combined effect of Ro and RLX on cAMP accumulation were studied in epithelial glands of 20 endometrial specimens obtained during different stages of the menstrual cycle. When epithelial glands were incubated with Ro alone, the cAMP concentration in glands from proliferative endometria was 120 +/- 67 pmol/mg protein (n = 6, means +/- SD), significantly higher than that of secretory endometria, 42 +/- 37 (n = 14, p = 0.007). RLX and Ro caused an additional increase of cAMP accumulation, 2- to greater than 10-fold increase over the sample incubated with Ro alone. There was no significant difference between proliferative and secretory phases (500 +/- 410, n = 6, and 470 +/- 300, n = 14, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

PubMed1987

Antisera against estrogen synthetase from human placental microsomes. Antibody characterization and cross-reactivity studies in other organs.

Antibodies were obtained against both protein components of the cytochrome P-450 enzyme system responsible for estrogen biosynthesis, estrogen synthetase (aromatase), from human placental microsomes. The antiserum against the NADPH-cytochrome P-450 reductase component (antiserum denoted RE-DFBIV) gave a single major band at the Mr of the authentic enzyme by immunoblotting after electrophoretic separation of SDS-solubilized microsomes and inhibited both the reductase and aromatase activities in human placental and endometrial microsomes (Tseng, L. and Bellino, F.L. (1985) J. Steroid Biochem. 22, 555-557) and in homogenates of cultured aromatase-stimulated human endometrial stromal cells and human ovarian microsomes. The antiserum against the cytochrome P-450 component of aromatase (antiserum denoted P45FBIII) also gave a single band at the Mr of the authentic protein by immunoblotting after electrophoresis, and inhibited aromatase activity in homogenates of human placental microsomes, ovarian and decidual particulate fractions and cultured aromatase-stimulated endometrial stromal cells. This antiserum had no effect on NADPH-cytochrome c reductase activity in any of the systems studied. We conclude that these antiserum preparations separately recognize the NADPH-cytochrome P-450 reductase and cytochrome P-450 components of aromatase in human placenta, ovary, decidua and endometrium. Epitopes on these aromatase component proteins involved in enzyme activity are shared among these various human tissue sources.

Adult↗

PubMed1987

Progestin-dependent effect of forskolin on human endometrial aromatase activity.

We have previously demonstrated that the aromatase activity in human endometrial stromal cells is stimulated by progestin and enhanced by oestrogen. In this study, we have investigated the effect of forskolin (Fk), an agent that stimulates the hormone-sensitive adenylate cyclase in mammalian cells, on the intracellular cAMP content and aromatase activity in endometrial stromal cells in primary culture. Stromal cells were isolated from proliferative and secretory endometria and were individually cultured in nutrient medium or medium supplemented with medroxyprogesterone acetate (MPA), oestradiol (E2) and Fk, separately or in combination. The intracellular cAMP content of stromal cells was increased after incubation with Fk. Stromal cells treated with Fk alone or FK and MPA for 1-3 days sustained the elevated intracellular cAMP content but 90% of this nucleotide was released to the medium. Aromatase activity was either not affected or was increased up to 5-fold over the control by Fk alone. Forskolin exerted a synergistic effect upon aromatase activity in the presence of progestin or progestin and oestradiol. Sequential incubation of the stromal cells with MPA and then Fk indicated that the additional increase in aromatase activity caused by Fk occurred after 24 h of incubation. These results demonstrate that intracellular cAMP exerts a stimulatory effect on aromatase activity in progestin-conditioned stromal cells. We also investigated whether the endometrial aromatase activity changes in vivo during the reproductive cycle by measuring the activities in endometrial specimens obtained from women during their reproductive age.(ABSTRACT TRUNCATED AT 250 WORDS)

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

PubMed1987

Effect of relaxin on aromatase activity in human endometrial stromal cells.

Previous studies have shown that the aromatase activity in human endometrial stromal cells was stimulated by progestin and enhanced by estrogen and forskolin (Fk), an agent that stimulates the accumulation of intracellular cAMP. Present study was undertaken to investigate whether any peptide hormone would affect endometrial aromatase activity. Stromal cells were isolated from normal proliferative and secretory endometria and cultured in nutrient medium. Porcine relaxin (RLX) was added to culture medium individually or in combination with medroxyprogesterone acetate (MPA) and estradiol (E2). Cells treated with RLX alone did not affect the aromatase activity. RLX, however, exerted a synergistic effect on aromatase activity in the presence of MPA or MPA plus E2. On the other hand, human CG, epidermal growth factor, human PRL, and insulin did not increase the aromatase activity in the presence or absence of MPA and E2 studied in a limited number of specimens. The progestin-dependent effect of RLX on aromatase activity was dose dependent indicating that the biological effect of RLX is mediated through a saturable mechanism. When RLX was added to MPA-pretreated cells, additional increase of aromatase activity was seen after 24 h incubation indicating that the action of RLX on stromal cells is not an acute effect. Antiprogestin, RU486, inhibited the stimulation of aromatase activity in both MPA and MPA plus RLX treated cells. RLX has either no effect or a moderate increase (up to 2-fold over the control) on intracellular cAMP content. On the other hand, Fk increased the intracellular cAMP level and enhanced the aromatase activity in the presence of progestin. Also RLX did not replace the effect of Fk since additional increase of aromatase activity was noted when stromal cells were incubated with MPA plus RLX plus Fk in comparison to MPA plus RLX or MPA plus Fk. These results suggest that the action of RLX on stromal cells may be mediated through an intracellular messenger independent of cAMP. Present studies provide evidence that RLX exerts a synergistic effect on aromatase activity in the presence of progestin in human endometrial stromal cells. It is evident that human endometrium is a target organ of RLX.

Aromatase↗

PubMed1987

Regulation of prolactin production by progestin, estrogen, and relaxin in human endometrial stromal cells.

Human decidua synthesizes and secretes PRL. We identified the PRL synthesized in endometrial stromal cells and investigated the effect of medroxyprogesterone acetate (MPA), estradiol (E2), porcine relaxin (RLX), and RU486, an antiprogestin, on PRL production by stromal cells from non-pregnant endometrium in primary culture. Stromal cells were isolated from proliferative and secretory endometria and individually cultured in nutrient medium or medium supplemented with different hormone(s). The immunoreactive PRL isolated from culture medium of hormone-stimulated stromal cells was identified and compared to pituitary PRL. Bio-Gel elution pattern and mol wt analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting showed that PRL produced by stromal cells had properties identical to those of pituitary PRL. In addition, PRL mRNA was identified in hormone-stimulated stromal cells using human pituitary PRL cDNA as a hybridization probe. Analysis of mRNA by Northern blotting showed that the size of PRL mRNA isolated from stromal cells was indistinguishable from that of PRL mRNA in human decidua and pituitary tissue. These results indicated that PRL measured in culture medium was synthesized de novo by stromal cells. The PRL content in culture medium was quantitated by RIA. The PRL production rate in stromal cells cultured without hormones ranged from 6-10 ng/day.mg cell protein. After 4-5 days of incubation with RLX or MPA alone, the PRL production rate increased about 2- to 3-fold over the control value. E2 alone had either no effect or slightly decreased the stromal cell PRL production rate. Stromal cells responded to 0.02 microM MPA, and the maximal response was at 0.1-1 microM MPA. A further increase in PRL production was found when stromal cells were treated with a combination of MPA and E2 and MPA, E2 and RLX. In the presence of MPA or MPA and E2, 0.1 ng/ml relaxin increased the PRL production rate. A potent progestin antagonist, RU486, inhibited PRL production in stromal cells treated with MPA, MPA and E2, or MPA and RLX. These results indicate that endometrial PRL production is regulated by the combined effects of steroid hormones (progestin and estrogen) and a peptide hormone (relaxin).

Cells, Cultured↗

PubMed1986

Endocrine aspects of human uterine sarcoma: a preliminary study.

The biologic effect of estrogen and progesterone in human uterine sarcoma is poorly understood in comparison to that of endometrial adenocarcinoma. In an attempt to elucidate the endocrine status of these tumors, we have investigated the ability of these tumors to synthesize estrogen by measuring the aromatase activity and studied the effect of aromatase inhibitors on the activity. In addition, the effect of estrogen and progesterone on aromatase activity and the growth pattern of these tumors were studied in cell culture and athymic mice systems. Aromatase activities in eight uterine sarcomas ranged from 0.7 to 37 fmol/hr X mg protein, which were within the range or higher than the activity found in normal proliferative endometrium (0.5 to 3 fmol/hr X mg of protein, means = 1.6, n = 10). These results indicate that uterine sarcomas are capable of producing estrogen. However, the enzyme activity showed no correlation with the morphology of tumors or the age of patients. Results from the kinetic studies of aromatase activity in one of the uterine sarcomas indicated that 19-nortestosterone, testolactone, and aminoglutethimide (the most effective one) inhibited aromatase activity. In addition, induction of aromatase activity in two uterine sarcomas was investigated in cell cultures. Progesterone caused an eightfold increase in activity in a sarcoma that was estrogen and progesterone receptor positive but had no effect in a tumor that was estrogen and progesterone receptor negative. The growth rate of two estrogen/progesterone receptor-negative uterine sarcomas was studied in cell culture and in athymic mice. Progestin, but not estrogen, reduced the growth rate in both systems; 30 nmol/L of estrogen had no effect on the growth rate. In summary, we have found that human uterine sarcoma is able to synthesize estrogen. Progesterone is able to induce the aromatase activity in estrogen/progesterone receptor-positive tumors, and progesterone also suppresses the tumor growth rate in estrogen/progesterone receptor-negative tumors. These results suggest that a select group of uterine sarcomas is sensitive to steroid hormone and that progesterone may be potentially beneficial for therapeutic treatment of select uterine sarcomas.

Adult↗

PubMed1986

Cancer antigen 125 is produced by human endometrial stromal cells.

Cancer antigen 125 (CA125) is an antigenic determinant defined by a murine monoclonal antibody and is present on the surface of some ovarian tumours. Using an immunoradiometric assay CA125 immunoreactivity was found in amniotic fluid and decidual extracts, hence the possibility of an endometrial origin of CA125 in pregnant and non-pregnant women was investigated. First-trimester decidual explants produced CA125 in vitro and cycloheximide significantly reduced the concentration of CA125 both in the medium and in the tissue. CA125 was also produced in primary culture of human endometrial stromal cells, its concentration in the medium being significantly higher with cells obtained during the proliferative and early secretory phases compared to those obtained during the late secretory phases. Medroxyprogesterone acetate (MPA, 1 mumol/l) induced a significant inhibition of CA125 production. This effect could be blocked by oestradiol (E2, 36 nmol/l) or the antiprogesterone RU486 (10 mumol/l). In women with endometriosis, the circulating levels of CA125 increased with the severity of the disease and were found to be significantly higher when compared to those of healthy volunteers. Gonadotrophin-releasing hormone or Danatrol therapy significantly reduced the CA125 levels. The endometrium, decidualized or not, seem to be capable of producing CA125, and this production is evidently correlated with endometrial cell growth and/or activity.

Antibodies, Monoclonal↗

PubMed1986

In vitro release of pregnancy-associated plasma protein-A (PAPP-A) by human endometrial cells.

Evidence has now accumulated to sustain the idea that pregnancy-associated plasma protein-A (PAPP-A) is not pregnancy specific: it can be localized immunohistochemically in nonpregnant human endometrium. Thus, it was of interest to see if a primary cell culture of human endometrial cells was capable of producing PAPP-A. Immunoreactive PAPP-A-like material was detected in the culture medium of glandular as well as stromal cells. The presence of PAPP-A in endometrial culture medium was specific and could not be attributed to a nonspecific protease effect on the tracer used in radioimmunoassay. The production rate of PAPP-A by stromal cells could be enhanced by the addition of medroxyprogesterone acetate (MPA). Estradiol (E2) alone or in combination with MPA did not modify the production rate of PAPP-A. The production rate of PAPP-A by glandular cells remained unchanged after treatment with MPA and/or E2. These results confirm that in nonpregnant women PAPP-A is a progesterone-dependent protein produced by the endometrium.

Cells, Cultured↗

PubMed1986

Modulation of aromatase activity in human endometrial stromal cells by steroids, tamoxifen and RU 486.

The regulation of aromatase activity (AA) in human endometrial stromal cells by various steroids was studied in primary cell culture. Various progestins, but not androgens or glucocorticoids, stimulated AA. Medroxyprogesterone acetate (MPA) was the most potent progestin. Estrogen (E) alone did not change the activity but it potentiated the stimulation of AA by progestin. Biphasic regulation of AA by progestin was noted in both time- and dose-dependent manners. Endometrial AA was stimulated by MPA and reached the maximum rate between 2-5 days of incubation with subsequent decline of AA in prolonged culture. When stromal cells were treated with MPA (0.03 to 30 microM) for 3 days, AA was increased over the control at all the concentrations tested. The maximum was found at doses between 0.1-1 microM. The activities reduced steadily from the maximum stimulation to less than 50% when the concentration of MPA increased from 1-30 microM. In addition, initial treatment of stroma cells with MPA (1-3 days) resulted in further increase of activity after progestin withdrawal. The enhancement of the induction of AA by E did not alter the biphasic pattern regulated by progestin alone, i.e. E enhanced both the stimulation and the decay of AA. The time study of the effect of E showed that enhancement of AA required at least 10 h of incubation of E with MPA conditioned cells. The effect of E is dose dependent between 0.04-40 nM and shows the greatest effect in the presence of MPA between 0.01-1 microM. The optimal concentrations of E and progestin that stimulate AA in culture are similar to the plasma concentrations after pregnancy, suggesting that the physiological function of the endometrial aromatase is at the time of decidualization. The effects of antiprogestin, Ru 486, and antiestrogen, tamoxifen (TAM), on AA were studied. Ru 486 or TAM alone did not alter AA. Ru 486 inhibited the MPA stimulated AA in a dose-dependent manner suggesting that the effect of progestin may be mediated through a receptor mechanism. Enhancement, but no inhibitory effect, was observed when cells were treated with TAM + MPA and TAM + MPA + E. The effectiveness of Ru 486 to inhibit the induction of AA in endometrial cells may be of primary importance for contraception.

Adult↗

PubMed1985

Inhibition of aromatase and NADPH cytochrome c reductase activities in human endometrium by the human placental NADPH cytochrome c reductase antiserum.

The cross-reactivity of human placental microsomal NADPH-cytochrome c reductase antiserum, REDFBIV, against the endometrial reductase alone and as a component of the endometrial aromatase was investigated. Human endometrial particulate fractions were incubated with various amounts of REDFBIV for 1 h at 4 degrees C and both enzyme activities were measured at the end of incubation. The extent of inhibition of these endometrial enzymes was compared with the ability of this antiserum to inhibit the placental microsomal reductase and aromatase activities. The antiserum effectively inhibited the activities of both enzymes in both tissues in a dose dependent manner with aromatase activity inhibited to a greater extent than reductase activity. These results indicate the antiserum to the placental microsomal NADPH-cytochrome c reductase component of aromatase recognizes the reductase component of the aromatase enzyme system in endometrium.

Aromatase Inhibitors↗

PubMed1985

Estrogen sulfotransferase in human placenta.

Human placental estrogen sulfotransferase (ESFT) was partially purified from the term placental cytosol by (NH4)2SO4 precipitation and agarose gel chromatography. Additional purifications caused a rapid loss of the enzyme activity. The activity was abolished by isoelectrofocusing but partially retained by chromatofocusing. The value of pI of human placental ESFT is 5.8 and the same value was obtained for bovine adrenal ESFT. The enzyme protein was able to bind to the affinity resin, estradiol-17-hemisuccinyl-1,2-diaminododecane sepharose 4B, but difficult to be extracted by estradiol (E2). The extract of the affinity resin showed one major protein band at 68,000 dalton on SDS-polyacrylamide gel electrophoresis. Kinetic studies using partially purified ESFT revealed that E2 is the best substrate for this enzyme. The relative rate of sulfurylation of E2, estrone, estriol and dehydroepiandrosterone at 4 microM (Km for E2) is 1, 0.3, 0.08 and 0.08, respectively.

Chromatography, Affinity↗

PubMed1984

Estrogen synthesis in human endometrial epithelial glands and stromal cells.

Biosynthesis of estrogen was studied in human endometrial epithelial glands and stromal cells. Intact epithelial glands and stromal cells were isolated from human normal proliferative and secretory endometrial specimens. The isolated glands and stromal cells were separately incubated with 10 nM [3H]testosterone in nutrient medium for 20 h in an incubator. Only estrone and estradiol were formed in stromal cells and in epithelial glands in the proliferative phase. Four types of estrogens: estrone, estradiol, estrone sulfate and estradiol-3-sulfate were isolated from the secretory epithelial glands. The capacity of aromatization is higher in stromal cells than that in glands. The highest capacity of aromatization was found in stromal cells in the proliferative phase, 58 +/- 30 fmol/mg protein (means +/- SD, n = 10) followed in order by stromal cells in the secretory phase, 30 +/- 18 (n = 6), and the epithelial glands in the proliferative and secretory phase, 22 +/- 12 (n = 10) and 4.3 +/- 1.2 (n = 6), respectively. These results indicate that the aromatase in endometrium is distributed in both stromal cells and epithelial glands. The capacity of aromatization varies in the 2 phases of the menstrual cycle with a significant decrease in activity of the epithelial glands in the secretory phase. The capacity of aromatization was also examined when stromal cells were incubated with various concentrations of [3H]T. The apparent Km, estimated from the concentration of delta 4-androgens in cells, is about 27 nM, indicating that the endometrial aromatase has a considerably high affinity to delta 4-androgens.

Endometrium↗

PubMed1984

Synthesis and biological activity of a new class of cytotoxic agents: N-(3-oxoprop-1-enyl)-substituted pyrimidines and purines.

The 1-(3-oxoprop-1-enyl) derivatives of thymine and cytosine and the corresponding 9-substituted derivatives of adenine and guanine (products of degradation of DNA by bleomycin, Fe2+, and O2) have been synthesized and tested for biological activity. The thymine and adenine compounds are highly cytotoxic to a variety of tumor cell lines and inhibit macromolecular synthesis in cultured HeLa cells. Structure-activity studies, based primarily on the pyrimidine derivatives, reveal that the most potent inhibition occurs when the propenal group is located on the 3-nitrogen of a 2'-deoxyribonucleoside. The 3-(3-oxoprop-1-enyl) derivatives of thymidine, 2'-deoxyuridine, and 5-iodo-2'-deoxyuridine powerfully and selectively inhibit incorporation of thymidine into DNA at concentrations (IC50 approximately equal to 0.5 microM) comparable to those observed with idoxuridine. Active compounds in this series react readily with nucleophiles containing primary amino and sulfhydryl groups. The results of this study provide a basis for the development of a new class of cytotoxic agents.

Aldehydes↗

PubMed1984

Effect of estradiol and progesterone on human endometrial aromatase activity in primary cell culture.

Isolated human endometrial stromal cells were cultured in RPMI 1640 medium containing insulin, antibiotics and 10% fetal calf serum. After the stromal cells developed a confluent monolayer, estradiol (E2), progesterone (P), or both were separately added to the culture medium and cells were continuously cultured for various periods of time. Aromatase activity was measured in control and hormone-treated cells by incubating the intact cells with [3H]testosterone and isolating the estrogens at the end of incubation. E2 alone did not change the aromatase activity. P caused an 8- to greater than 40-fold increase over the control values (1 to 7 fmol/mg protein X h), and the activity was further increased in the presence of E2 (20- to 100-fold). The stimulation of aromatase activity by P was found to be both time- and dose-dependent and blocked by actinomycin D. Maximal stimulation was reached after the stromal cells were treated with 300 nM P for 3 days. At 30 nM P, a concentration similar to the plasma level during the luteal phase of the menstrual cycle, 80% of maximal stimulation was noted. These results indicate that P stimulates aromatase in endometrial stromal cells and E2 potentiates this stimulation. Much smaller effects of E2 and P on the aromatase activity were noted in endometrial epithelial glands.

Aromatase↗

PubMed1984

Preliminary studies of aromatase in human neoplastic endometrium.

The capacity of aromatization in 15 neoplastic human endometrial specimens was investigated. Viable tissue fragments were incubated with [3H]testosterone (10 nM) at 37C for 20 hours. Various estrogens were isolated from the incubated tissues and medium. The mean value of estrogen synthesized in 12 cases of endometrial adenocarcinoma (16.0 +/- 11, means +/- SD fmol/mg protein), is approximately two and five times higher than that of proliferative and secretory endometria, respectively. The highest capacity was found in three mixed mullerian tumors (means = 145 fmol/mg protein). These findings indicate that the malignant endometria, in particular the mixed mullerian tumors, are able to synthesize estrogen in a capacity higher than that in normal endometria. Endometrial aromatase may play an important role in promoting cell growth in estrogen-sensitive tumors.

Adenocarcinoma↗

PubMed1983

Malignant mixed Müllerian tumor of the endometrium in a young woman with polycystic ovaries.

A 19-year-old female with Stein-Leventhal syndrome and polycystic ovaries was found to have a malignant mixed Müllerian tumor (MMMT) of the uterus with superficial myometrial invasion. This patient is the youngest reported with MMMT of the endometrium. The association of endometrial malignancies and polycystic ovaries is reviewed. The tumor was found to have above normal levels of estradiol and progesterone receptors. A possible role of estrogen stimulation in the genesis of some MMMTs is suggested.

Adult↗

PubMed1983

Estrogen sulfatase and estrogen sulfotransferase in human primary mammary carcinoma.

Estrogen sulfatase (ES) and estrogen sulfotransferase (ESFT) activities were measured in a group of primary breast tumors. The mean value of ES activities, measured in 66 breast tumor specimens, was 0.9 nmol of estrone formed from estrone sulfate/mg tissue protein per hr regardless of the hormone receptor status of the specimen. However, the average value of the ESFT activity, expressed in nmol of estradiol-3-sulfate (E2S) formed from estradiol (E2)/mg of cytosol protein per hr, was found to be significantly higher in ER +/PGR + tumors (n = 26, 0.18 +/- 0.15, means +/- SD) than in ER -/PGR - tumors (n = 31, 0.08 +/- 0.06, P less than 0.005). Normal breast tissues also contain ES and ESFT but the activities were lower than those in tumors. When fresh breast tumor tissue fragments were incubated with radioactive E2 (0.4 nM) and E2S (3 nM) separately, E2 was not sulfurylated appreciably while E2S was extensively hydrolyzed to free estrogens indicating that the combined effect of ES and ESFT in breast tumor is favored towards the hydrolysis of estrogen sulfate. These results imply that the circulating estrogen sulfate could be utilized as the precursor of active estrogen to promote the cell growth in hormone sensitive tumors.

Breast Neoplasms↗