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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many New World primates such as the squirrel monkey have extraordinarily high plasma levels of steroid hormones including cortisol, testosterone, progesterone and vitamin D3. While plasma estrogen levels in female squirrel monkeys apparently are approximately the same as those found in other species no information is available for males. The present results indicate that the plasma levels of estrone (E1), estradiol (E2), and E1 sulfate are approximately 10-fold higher than those found in men. Comparative in vitro studies of androgen metabolism in genital skin fibroblasts indicate that squirrel monkey cells have higher aromatase and lower 5-alpha-reductase activity than human cells. Estimation of aromatase activity in vivo by a radiometric assay indicates that the high plasma estrogens are derived by peripheral conversion from testicular and/or adrenal androgens.
Steroids
PMID:Conversion of androgens to estrogens in the male squirrel monkey (Saimiri sciureas). 350 16

Tumor aromatase has been correlated with clinical response to treatment with aminoglutethimide in patients with estrogen receptor-positive advanced breast cancer. There was a significant positive relationship between aromatase status and likelihood of response to therapy, none of five patients with aromatase-negative tumors responding compared with 11 of 18 having aromatase-positive cancers. Measurement of in vitro aromatase in sequential biopsies of large primary tumors before and during treatment with aminoglutethimide-hydrocortisone showed a marked but paradoxical rise in activity following therapy. Assays of aromatase in adipose tissue from the different quadrants of mastectomy specimens from patients with breast cancer indicate that activity was always higher in quadrants associated with tumor as compared with non-involved quadrants. These results emphasize the importance of local estrogen synthesis within the breast in terms of both the natural history and behavior of breast cancers.
Steroids
PMID:The importance of local synthesis of estrogen within the breast. 350 15

Infusions of isotopically labeled [3H] androstenedione with measurement of [3H] estrone in normal breast and breast tumor tissue have been carried out in an attempt to determine the contribution that aromatization makes to the estrogen content of breast tissues. After infusion of [3H] androstenedione for 12h there was significant uptake of this steroid by normal breast and breast tumors. [3H] Estrone was detected in all samples of normal breast tissue examined so far but not in all tumors. Aromatase activity when measured in vitro was found to be higher in breast tumors than in fat next to the tumor or normal breast fat. Studies in which we have examined the effect of epidermal growth factor on aromatase activity in cultured breast adipose tissue suggests that the response may be influenced by a subject's menopausal status. Results from these preliminary studies suggest that the aromatization of androgens may make a significant contribution towards the estrogen content of some breast tumors and that growth factors may also be involved in regulating aromatase activity.
Steroids
PMID:Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies. 350 63

Androst-4-en-3-one analogs incorporating a trimethylsilyl or a trimethylsilylmethyl group at C-1, C-2 or C-19 were prepared and evaluated as inhibitors of aromatase. Only 10-[1-hydroxy-2-(trimethylsilyl)ethyl]estr-4-ene-3,17-dione inhibited human placental aromatase. Enzyme kinetic analysis revealed competitive inhibition [apparent dissociation constant (Ki) of 562 +/- 12 nM] associated with marginal time-dependent inhibition.
Steroids
PMID:Novel silylated steroids as aromatase inhibitors. 383 57

The suggestion has been made that the aromatase system from human placenta converting testosterone to estradiol-17 beta is localized to some extent in the mitochondrial fraction in addition to its microsomal origin. By comparing the characteristics of the "mitochondrial" aromatase with certain particularities of other mitochondrial or microsomal enzymes, especially those functioning in steroid hydroxylation, the conclusion has been reached that the mitochondrial and the microsomal aromatases are one and the same. Thus, in response to ultrasound treatment and in response to the addition of specific cofactors, the mitochondrial aromatase showed all the characteristics attributed to microsomal enzymes and was indistinguishable from the microsomal aromatase.
Steroids
PMID:Human placenta mitochondrial aromatase--fact or artifact. 384 41

Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.
Steroids 1985 Jul
PMID:Effects of ketoconazole on rat testicular steroidogenic enzymatic activities. 387 79

The effect of the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the synthesis of estradiol (1,3,5 (10)-estratriene-3,17 beta-diol) by granulosa cells from preovulatory follicles of rats, rabbits and humans was examined. Granulosa cells from all three species were incubated for 4 h without treatment (control) or in the presence of androstenedione (4-androstene-3,17-dione, 0.5 microM), 4-OH-A (5 microM), or both compounds together. Estradiol levels were determined in the medium and cells by radioimmunoassay. In all three species, estradiol synthesis was markedly increased by androstenedione and this increase was blocked by 4-OH-A. In the rabbit, however, 4-OH-A alone caused a small but significant increase in radioimmunoassayable estradiol. The apparent increase seen with 4-OH-A alone may be due to a metabolite of 4-OH-A that cross-reacts in the estradiol radioimmunoassay. With granulosa cells from humans, in which 4-OH-A is of potential therapeutic importance, no similar effect of 4-OH-A alone was observed.
Steroids 1985 Feb
PMID:Comparison of the effect of 4-hydroxy-4-androstene-3,17-dione on aromatase activity in granulosa cells from preovulatory follicles of rats, rabbits, and humans. 408 16

Using microsomes isolated from term human placentae kinetic analyses of each of the enzymes involved in estrogen synthesis from dehydroepiandrosterone sulfate have been carried out and the following parameters were found: sulfatase, Michaelis-Menten constant (Km) = 16,000 +/- 5,000 nM, maximum velocity (Vm) = 2.0 +/- 0.5 nmol X min-1 X mg protein-1; 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), Km = 15 +/- 3 nM, Vm = 1.8 +/- 0.4 nmol X min-1 X mg protein-1; aromatase, Km = 14 +/- 4 nM, Vm = 0.12 +/- 0.02 nmol X min-1 X mg protein-1. From these values one can predict that, theoretically, the rate-limiting enzyme in estrogen synthesis from dehydroepiandrosterone sulfate (DS) should change from the sulfatase at low concentrations of substrate to the aromatase at higher concentrations. In order to test this hypothesis we developed a system which allowed the formation of estrogens from DS, dehydroepiandrosterone, and androstenedione to be measured and the appropriate intermediates to be isolated. The sulfatase was found to be rate limiting at concentrations of DS below 2 microM and the aromatase was found to be rate limiting at higher concentrations. These data may explain why previous perfusion studies of human placentae indicated the sulfatase was the rate-limiting enzyme in estrogen synthesis yet in vitro studies found that it was the aromatase. Steroids previously shown to inhibit the 3 beta-HSD were examined for their ability to inhibit the formation of estrogens from DS. Although 3 beta-HSD activity was markedly inhibited this had little effect on the overall conversion of DS to estrogens, until high concentrations of inhibitors were used. The data also underline the importance of studying enzyme systems rather than single enzymes when studying steroid synthesis.
 ...
PMID:Kinetic studies on the formation of estrogens from dehydroepiandrosterone sulfate by human placental microsomes. 623 32

Estrogen secretion and estrogen synthetase (aromatase) activity are stimulated in human trophoblast cells (JAr line) after addition of 1 mM dibutyryl cyclic AMP plus 1 mM theophylline (dbT) to the growth medium. The data given here show that (a) the aromatase specific activity in homogenized cells increases linearly over a 96 hr incubation period after addition of dbT; (b) addition of inhibitors of macromolecular synthesis, cycloheximide or actinomycin D, to the culture medium at the time of addition of dbT abolishes the stimulation of aromatase activity; (c) mixing dbT-grown cells, containing increased aromatase activity, with control cells does not result in an aromatase specific activity higher than the expected average, suggesting that dbT-grown cells do not contain a factor present in excess which serves to stimulate aromatase in control cells; and (d) NADPH, included in vitro in the aromatase assay or incubated with the cells for 48 hr as well as being present in the aromatase assay, has no stimulatory effect on aromatase specific activity in homogenized cells.
Steroids 1981 Jan
PMID:Macromolecular synthesis is required for stimulation of estrogen synthetase activity by dibutyryl cyclic AMP plus theophylline in choriocarcinoma cell culture. 626 25

Decreased sperm counts and impaired sperm motility are present in a substantial proportion of men with varicocele. Elevations in the temperature of the affected testis, and increased spermatic vein estradiol (E2) concentrations have been found in some of these patients. To investigate the possibility that increases in temperature lead to a pattern of testicular steroidogenesis that results in increased E2 synthesis, we have examined the effects of temperature changes on the activities of four important testicular steroidogenic enzymes. 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase activities were measured in the microsomal fraction of rat, pig and horse testes. Incubations were performed at 34 degrees C, 36 degrees C, and 38 degrees C. The activities of all 4 enzymes increased with each 2 degrees C temperature elevation in roughly proportional amounts. We conclude that minor elevations in incubation temperature are associated with increases in the in vitro activity of four key testicular steroidogenic enzymes.
Steroids 1984 Mar
PMID:The effects of temperature on the activity of testicular steroidogenic enzymes. 633 11


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