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Biomedical subjects

J Fishman

Publications and source records attributed to J Fishman.

At least 127 records · Page 7Linked to original sources
PubMed1982

Biochemical mechanism of aromatization.

The aromatization of androgens to estrogens by placental aromatase involves three hydroxylations which take place in sequence. The first two occur at the C-19-methyl group while the site of the final and rate-determining hydroxylation has been identified as being at 2 beta. The product of this reaction collapses to estrogen by a rapid nonenzymatic mechanism. The absence of a direct relationship between the enzyme(s) responsible for estrogen formation and the end product results in an absence of product feedback inhibition, a consequence with potential physiological implications. The proposed mechanism of estrogen formation is supported by chemical, biochemical, and immunological evidence.

Aromatase↗
PubMed1982

Abnormal estrogen and androgen metabolism in the human with systemic lupus erythematosus.

Humans with SLE were studied with regard to their ability to metabolize estradiol and testosterone. Significant abnormalities in the patterns of metabolism of both classes of sex steroids were found. Estradiol hydroxylation at C-16 was more extensive in both males and females with SLE -- leading to more estrogenic metabolites; and testosterone oxidation was elevated in patients with SLE resulting in a decrease in total androgens. Some normal first degree relatives of patients with SLE also had abnormalities of estradiol hydroxylation.

Estradiol↗
PubMed1981

Mechanism of estrogen biosynthesis. Stereochemistry of C-1 hydrogen elimination in the aromatization of 2 beta-hydroxy-19-oxoandrostenedione.

19-Hydroxy[1 alpha-3H]androstenedione was synthesized and its specific activity was accurately determined. Upon aromatization of the above material by placental microsomal aromatase preparation, a process involving 1 beta hydrogen elimination, only 7.4% of the isotope was lost establishing the alpha orientation of the 3H at C-1 in the substrate. The 19-hydroxy[1 alpha]3H]androstenedione was used as the starting material in the synthesis of 2 beta-hydroxy-19-oxo[1 alpha-3H]androstenedione which therefore had the same specific activity and isotope orientation as its precursor. The nonenzymatic collapse of 2 beta-hydroxy-19-oxo[1 alpha-3H]androstenedione in pH 7.1 buffer to estrone was associated with the elimination of only 2.6% of the isotope indicating that this process proceeds also with stereospecific 1 beta hydrogen elimination. The stereochemistry of hydrogen loss in the nonenzymatic aromatization of the 2 beta-hydroxy-19-oxo derivative is therefore beta and identical with that of estrogen biosynthesis. This provides further evidence in support of the hypothesis that the final enzymatic hydroxylation of the aromatization sequence takes place at position 2 beta of the androgen substrate and that its product, the 2 beta-hydroxy-19-aldehyde, is the proximate precursor of estrogen with the final conversion occurring nonenzymatically.

Androstenols↗
PubMed1981

Increased 16 alpha-hydroxylation of estradiol in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is one of many chronic diseases with a predilection for the human female. The reasons for the high female to male (9:1) incidence remain unknown. The total extent of hydroxylation estradiol at either C-16 to more estrogenic metabolites or at C-2 to the catechol estrogens was determined by a radiometric method in the human. Comparing 23 SLE patients to 44 normal controls, an increase in the extent of hydroxylation toward the 16 alpha-metabolites was found in SLE (SLE 15.2 +/- 4.3%, range 8.8-30%; normal 9.1 +/- 2.3%, range 5.3-14.4%; P less than 0.001). Increased 16 alpha-hydroxylation was found in both males (SLE 13.2 +/- 3.0%, normal 8.3 +/- 2.1%) and females (SLE 15.7 +/- 5%, normal 9.9 +/- 2.2%) with disease when compared to normal subjects. In addition, studies of several other chronic diseases by the same method did not indicate a similar alteration in 16 hydroxylation. No change in hydroxylation at C-2 was found in male patients, but a decrease was found in female patients. These data suggest that increased hydroxylation of estradiol at C-16 occurs in SLE. The 16 alpha-metabolites have been shown to be potent estrogens, and these data might give some insight into the pathogenesis of the disease.

Adolescent↗
PubMed1980

Suppression of prolactin secretion in normal young women by 2-hydroxyestrone.

The nonuterotropic natural estrogen 2-hydroxyestrone administered to normal young women results in a prompt and profound suppression of serum prolactin in most of the subjects. With the exception of dopamine, this is the only endogenous material known to strongly inhibit prolactin secretion, and its action suggests that the physiological regulation of prolactin by estrogens in the human is dual in nature, consisting of stimulation by estradiol and inhibition by its catechol estrogen metabolite.

Adult↗
PubMed1980

Formation of 3H2O from [2-3H]- and [4-3H] estradiol by rat uteri in vitro: possible role of peroxidase.

The mitochondrial fraction of diethylstilbestrol-treated rat uteri, known to contain an estrogen-induced peroxidase, was able to catalyze the release of 3H2O from either [2-3H]- or [4-3H]estradiol. Hydrogen peroxide added to this system increased the yield of 3H2O but had no effect on mitochondrial preparations from ovariectomized rat uteri having only very low peroxidase activity. The reaction was inhibited by catalase and also occurred with lactoperoxidase in the presence of H2O2 but 2-hydroxyestradiol was not detected in any of these experiments. Under similar conditions, tyrosinase catalyzed the formation of the catechol estrogen with loss of 3H from [2-3H]- or [2,4,6,7-3H]- but not [4-3H]- or [6,7-3H]estradiol. It is proposed that the formation of 3H2O from 3H-labeled estradiol in the estrogen-treated rat uterus may occur by a peroxidative mechanism which does not necessarily result in hydroxylation of the steroid.

Animals↗
PubMed1980

Ewing's sarcoma of the hand following recurrent trauma; a case report.

A case of Ewing's Sarcoma of the thumb is described. Four years after a fracture of the first metacarpal, followed by a series of repeated traumata to the area, a tumour was discovered. According to Ewing's criteria of trauma induced malignancy, this case is highly suggestive to have been caused by trauma.

Adult↗
PubMed1980

Opiate regulation of estradiol-2-hydroxylase in brains of male rats: mechanism for control of pituitary hormone secretion.

Treatment of male rats with a single high dose of morphine (10 mg/kg, subcutaneously) results in a dramatic suppression of brain estradiol-2-hydroxylase activity. The suppression is blocked by naloxone and is decreased upon the development of tolerance. The injection of naloxone (0.4 mg/kg) alone produces a significant increase in brain estradiol-2-hydroxylase activity over control levels. The effects of the opiate agonists and antagonists on the activity of this brain enzyme coincide in degree and direction with their effects on plasma lutropin (luteinizing hormone) concentrations. Because the 2-hydroxyestrogens were shown to induce pituitary lutropin release, the present results indicate that the action of opiates, endogenous or exogenous, on pituitary gonadotropin release can be mediated by brain catechol estrogens.

Animals↗
PubMed1980

Radiometric analysis of biological oxidations in man: sex differences in estradiol metabolism.

The oxidative metabolism of estradiol was studied in normal men and women by a radiometric procedure that provides information on the totality of the biotransformations concerned. The release of 3H into body water from estradiol labeled with 3H in the 17 alpha, 16 alpha, and C-2 positions permits measurement of the rate and extent of 17 beta-ol oxidation and of the competing hydroxylations at C-2 and 16 alpha, which lead to products with different biologicaly properties. In both men and women the 17 beta-ol oxidation is the most rapid transformation, followed by 2-hydroxylation and finally by 16 alpha-hydroxylation. Hydroxylation at C-2 predominates by a faccto of 2-4 over 16 alpha-hydroxylation. In men a large fraction (37%) of the substrate is unmetabolized at any of the three sites and is not excreted in urine; in women the corresponding fraction is only 18%. The estradiol fraction that does undergo metabolism is hydroxylated at C-2 vs. 16 alpha to a greater extent in women than in men. These major sex differences in the metabolism of estradiol in the human may have an important influence on the expression of the biological actions of the hormone. The radiometric technique used in this study can be generally applied to study the oxidative transformations of hormones, drugs, and other exogenous chemical that can be specifically labeled at reactive sites.

Aryl Hydrocarbon Hydroxylases↗
PubMed1980

False aneurysm of the posterior tibial artery complicating fracture of the tibia and fibula.

A false aneurysm of the posterior tibial artery associated with a fracture of the tibia and fibula is described. A review of the English language literature of the last 15 years revealed only six other similar cases. The physician should bear in mind that a persisting painful swelling at the fracture site of the leg might be the only clinical sign of a false aneurysm developing in one of the tibial vessels.

Aneurysm↗
PubMed1980

Suppression of prolactin and gonadotropin secretion in post-menopausal women by 2-hydroxyestrone.

An infusion of 2-hydroxyestrone given to estrogen primed post-menopausal women resulted in a rapid and total suppression of serum prolactin. Serum LH responded with an initial rise followed by a 30% decrease below baseline values. Serum FSH exhibited a significant suppression below preinfusion levels. The catechol estrogen had no effect on serum LH, FSH and PRL in post-menopausal women who were not pretreated with estrogens. This impact of 2-hydroxyestrone on pituitary hormone secretion provides for the physiological role of this non-uterotropic estrogen in the neuroendocrine mechanisms of the human.

Estrone↗
PubMed1980

Stimulatory effect of 2-hydroxyestradiol on prolactin release in hypogonadal women.

Administration of an intravenous bolus (1.0 mg) or a constant rate infusion (250 microgram/h for 4 h) of 2-hydroxyestradiol (20H-E2) to hypogonadal women, resulted in no discernible alteration in the circulating levels of LH and FSH. In contrast, progressive increments in the release of prolactin were unequivocally detected at 4.5 h after receipt of the bolus and 2.5 h following the initiation of the infusion.

Adult↗