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J Fishman

Publications and source records attributed to J Fishman.

At least 37 records · Page 2Linked to original sources
PubMed1986

16 alpha-hydroxylation of estradiol: a possible risk marker for breast cancer.

From these results we may conclude that estradiol 16 alpha-hydroxylation is highly correlated with tumor incidence, and that the reaction is partly regulated by MMTV and the rest by genetic influences. Elevated hydroxylation appears to be an autosomal dominant trait that is highly specific for estradiol. It is also pertinent that the product of the 16 alpha-hydroxyestrone reaction is a potent estrogen that is capable of binding covalently to amino acids and nucleotides, including the estrogen receptor molecule. The results obtained in these studies establish the usefulness of the mouse model for studying the interrelationship between enhanced 16-hydroxylation of estradiol and the incidence of mammary tumors.

Age Factors↗
PubMed1986

Effect of catechol estrogens on the preovulatory content of luteinizing hormone-releasing hormone in the median eminence of the rat.

Cycling rats injected with 2-hydroxyestrone or 2-hydroxyestradiol at 09.00 or 10.00 h in the morning of proestrus do not express the normal preovulatory LH surge in the afternoon of the day. The LHRH content of the median eminence in control animals decreases sharply in the afternoon from elevated noon and morning levels. The catechol estrogen-treated rats fail to show the decrease. Thus the catechol estrogens block the LH surge at its usual time by influencing the changes in the concentration of LHRH in the median eminence on proestrus. Since the catechol estrogens have short biological half-lives, their effect on the LHRH content in the afternoon must originate in the morning at the time of the endogenous estradiol (E2) peak. These results have implications in the physiological processes responsible for the positive feedback of estradiol on the preovulatory LH surge in the rat.

Animals↗
PubMed1986

Inhibition of the preovulatory prolactin surge in the rat by catechol estrogens: functional and temporal specificity.

Catechol estrogens, administered iv to cycling rats on the morning of proestrus, were able to block the preovulatory PRL surge on the afternoon of the same day. Only catechol estrogens with a low affinity for the estrogen receptor, such as 2-hydroxyestrone and 2-hydroxyestradiol-17 alpha were effective in this respect, while the estrogenic catechol estrogen 2-hydroxyestradiol was unable to influence the PRL surge. The effectiveness of the PRL surge abolition was highly dependent on the state of the endogenous estradiol levels at the time of administration. Only doses given just before the peak secretion of estradiol were effective in blocking the PRL surge. Despite similarities in the inhibition of the preovulatory LH and PRL surges by catechol estrogens, these are considered to occur by different mechanisms because the LH secretion is blocked by all catechol estrogens, while the PRL surge is affected only by catechol estrogens with no estrogen agonist properties. The catechol estrogen blockade of the PRL surge may have physiological parallels and provides a useful probe of the mechanisms of the estrogen-PRL axis.

Animals↗
PubMed1985

The formation at 37 C of a nondissociable receptor-estradiol complex.

The receptor-estradiol complex formed in rat uterine cytosol when heated at 37 C converts from a dissociable to a nondissociable form. The conversion is best observed in cytosols pretreated with charcoal at 0 C which renders the subsequently formed receptor-estradiol complexes thermostable at 37 C. In the presence of dithiothreitol the heated complex remains dissociable. Tamoxifen does not form nondissociable complexes with the estradiol receptor. It is proposed that the nondissociable form of the receptor complex is a required phase in the mechanism of estradiol action.

Animals↗
PubMed1985

Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans.

In this report, we describe our findings on the relationship between estradiol 16 alpha-hydroxylation and mammary tumor incidence. A close correlation between the two has been demonstrated with 16-hydroxylation being elevated in strains with a high incidence of tumors, such as RIII and C3H, and low in strains with a low incidence of cancer, such as C57BL. The extent of reaction is highly reproducible and unaffected by age or presence of overt mammary tumors. Studies on the inheritance of estradiol 16 alpha-hydroxylase showed that it is inherited as an autosomal dominant and is not correlated with estradiol 2-hydroxylase or androgen and progestin 16 alpha-hydroxylases. In addition, the reaction was shown to be markedly enhanced by the presence of murine mammary tumor virus and diminished in the absence of the virus. These studies establish a relationship between genetics, hormonal factors, and murine mammary tumor virus, the three key factors in mammary tumorigenesis.

Age Factors↗
PubMed1985

Castration affects male rat brain opiate receptor content.

We previously reported that saturable stereospecific binding of [3H]-naltrexone in rat brain homogenates prepared from castrated male rats was greater than the corresponding binding in intact animals. We now report that we have replicated these results and that the difficulty of other investigators in observing these differences is due to methodological factors. Specifically, when samples were filtered individually and rapidly, differences between castrated and intact rats were maintained. The increase in binding was also observed when tissues were washed to remove endogenous opioids prior to incubation, when [3H]-naloxone was used as the ligand, and when various antagonists were used as displacers in the radioreceptor assay.

Animals↗
PubMed1979

Low urinary estrogen glucuronides in women at risk for familial breast cancer.

Daily (12-hour) urine collections taken throughout the menstrual cycle were obtained from 30 young women who by genetic analysis were at risk for familial breast cancer, and from 30 control women carefully matched for age, height, and reproductive history. Steroids in the urine were extracted by glucuronidase hydrolysis, and the primary glucocorticoid, androgen, and estrogen hormones and their metabolites were measured by radioimmunoassay. Highly significant differences were observed only in the case of estrone and estradiol, with the high-risk subjects exhibiting lower values that the controls. This endocrine abnormality in young women at risk for breast cancer may be a potential discriminant for identifying women at risk for the disease in the population at large.

Adult↗
PubMed1979

Endocrine profile in a patient with familial breast cancer: a case-control study.

Urinary and blood hormonal profiles were studied throughout a monthly cycle in a patient with familial breast cancer. Two comparison cohorts (one high-risk and one low-risk) were studied concurrently. Findings disclosed that our breast cancer-affected patient showed a distinctive hormonal pattern characterized by significant elevation throughout the cycle of plasma estrone, estradiol, and prolactin. Save for a depression in plasma FSH in the early follicular phase, this hormone, as wells as LH and progesterone patterns in our patient, were similar to the comparison cohorts. Urinary estrone and estradiol patterns in our patient were elevated early in the follicular phase. Our patient also showed a depression in urinary estrone, estradiol, and estriol following ovulation, which persisted throughout the luteal phase. Blood and urinary hormone patterns in the high-risk cohort were not demonstrably different from the low-risk cohort, with the exception of plasma prolactin. The results on the latter hormone showed an unexpected significant depression throughout most of the menstrual cycle in this low-risk cohort. We conclude that estrone and estradiol elevations, as clearly evidenced in our breast-cancer-affected patient, may provide clues that ultimately might be used as an etiologic discriminant for breast cancer risk and which may also play a pathogenic role in this disease. Since this involved a single patient, our conclusions must be interpreted cautiously.

Adult↗
PubMed1979

Alterations of estrogen metabolism in systemic lupus erythematosus.

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.

Adolescent↗
PubMed1979

Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion.

The biological activity of a series of natural catechol estrogens was examined under conditions of continuous administration. 2-Hydroxyestradiol (2OH-E2), 2-methoxyestradiol (2MeOE2), 4-hydroxyestrone (4OH-E1), 4-methoxyestradiol (4MeOE2), 2-hydroxyestrone (2OH-E1), and 4-methoxyestrone (4MeOE1) were delivered at the rate of 1 microgram/h from osmotic pumps implanted in ovariectomized rats. Uterine growth and plasma LH concentrations were measured 24, 48, and 72 h after implantation. Little or no uterotropic activity was exhibited by the 2-hydroxylated metabolites 2OH-E1 and 2MeOE2 at any interval, while 2OH-E2 exhibited anomalous uterotropic activity, which terminated at 48 h. The 4-hydroxylated compounds 4MeOE2, 4OH-E1, and 4MeOE1 all produced substantial and progressive uterine growth. Tonic LH secretion was suppressed by 2OH-E2, 4OH-E1, and 4MeOE1 in proportion to their uterotropic activity. 2OH-E1 was the only substance which increased plasma LH concentrations. The nuclear receptor occupancy by 2OH-E2 was substantially shorter than that of E2. Binding studies of the test and other related estrogens to the uterine cytosol estradiol receptor showed that their relative binding affinities in many instances did not correlate with their biological activities.

Animals↗
PubMed1979

Effect of flutamide on estradiol metabolism.

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.

Anilides↗
PubMed1979

Absence of measurable 2-hydroxyestrone in the rat brain: evidence for rapid turnover.

The free 2-hydroxyestrone content of female rat brains was measured by two independent methods, including a direct radioimmunoassay and enzymatic conversion to stable O-methylated derivatives followed by a specific radioimmunoassay for the latter. The sensitivities of the two procedures were 10 pg and 5 pg respectively and the recoveries were greater than 85%. Neither assay method was able to detect any measurable endogenous 2-hydroxyestrone in the female rat brain at any stage of the ovulatory cycle. It is suggested that a high turnover rate of 2-hydroxyestrogens in the rat brain precludes the accumulation of detectable quantities of these metabolites in central tissues.

Animals↗
PubMed1978

Plasma hormone profiles of young women at risk for familial breast cancer.

The plasma hormone concentrations of 30 young women, who were judged by genetic analysis to be at high risk for familial breast cancer, were compared with those of 30 matched controls identified as at low risk for the disease. The hormone measurements were obtained every second day throughout the menstrual cycle, and the results were analyzed in terms of follicular, luteal, and full-cycle mean concentrations. Comparison was carried out in a paired fashion with each high-risk and low-risk pair matched closely for height, weight, age, and reproductive history. No statistically significant differences were found in prolactin, gonadotropin, estrone, estradiol, or estriol plasma concentrations although the high-risk group displayed consistently lower values in all of the above except estriol.

Adult↗