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Biomedical subjects

J Fishman

Publications and source records attributed to J Fishman.

At least 145 records · Page 8Linked to original sources

Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology.

Metabolism of estradiol in men with cirrhosis and subjects with systemic lupus erythematosus results in an excessive formation of 16 alpha-hydroxyestrone. Examination of the biological activity of this metabolite showed that it is a potent uterotropic agent and that it exhibits minimal affinity for the human sex hormone-binding globulin. These biological characteristics are consistent with a hyperestrongenic response to the substance, which may be reflected in the pathology and etiology of these diseases.

Animals↗

Response of serum prolactin to catechol estrogen in the immature rat.

The response of serum prolactin to the catechol estrogens, 2-hydroxyestrone (2-OH E1) and 2-hydroxyestradiol (2-OH E2) and their primary estrogens, estrone (E1) and estradiol (E2), was studied in 35-day-old male rats. The subcutaneous administration of 50 microgram of 2-OH E1 or 2-OH E2 significantly suppressed serum prolactin concentrations, but they were not significantly altered by the administration of 50 microgram of E1 or E2.

Animals↗

Early diagnosis at the CDH clinic.

In 1978, 488 of 8,211 registered newborn babies in the Haifa area were referred to us for suspected congenital dislocation of the hip. The findings were as follows: normal, 53%; justifying further follow-up, 40.5%; subluxation, 4% (19 cases); and dislocation, 2.5% (12 cases). The infants with subluxation or dislocation were not older than six months. Treatment of dislocation included: open reduction, 1; closed reduction under general anesthesia, 4; and reduction and treatment by abduction splints, 7. After this treatment, all hips were stable. Abduction splints were used in the 19 subluxation cases; there was no aseptic necrosis of the femoral head. All infants with minor deviations in the hip joints, such as consistent limited abduction, delayed appearance of epiphyseal ossification center or acetabular dysplasia, were deliberately grouped under "justifying follow-up." It is possible that these minor deviations harbor the buds of early osteoarthritis.

Health Facilities↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗