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Query: UMLS:C0338671 (Steroids)
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Experiments in vitro on tissue from a feminizing adrenocortical carcinoma removed from a postmenopausal patient are described. Portions of the adrenal tumor were cultured. The effects of ACTH, prolactin, and other protein hormones on the synthesis and secretion of steroid hormones by the cultured tissue were studied. Steroids were extracted from the culture medium with ethyl acetate. Steroid production was determined by high resolution-mass fragmentography and by radioimmunoassay. Results suggest that in vitro neither growth hormone (GH) nor luteinizing hormone (LH), at the concentrations used, effectively stimulated the synthesis and secretion of estradiol-17beta by the adrenal tumor tissue. However, ACTH and prolactin with insulin, appearing to influence the action of both these hormones, stimulated the output of estradiol-17beta. Steroid was being synthesized during the 3-day culture period. The tumor tissue actively synthesized and secreted into the medium estrone as well as estradiol-17beta under the influence of ACTH and prolactin with insulin. Data also suggest that LH and GH were capable of influencing the synthesis and secretion of androstenedione by the tissue explants. No DNA sulphate was present in the media from the tumor tissue cultures before or after incubation with either ACTH or prolactin. Results from studies with normal adrenal tissue in culture indicated that DNA sulphate, DHA, and androstenedione were present in the culture medium after 3 days' incubation. In this report the concentration of endogenous estrone relative to estradiol-17beta and estradiol was found to be high. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumor tissue indicated a lack of specificity of the membrane receptor sites. High resolution-mass fragmentography had greater specificity than radioimmunoassay.
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PMID:In vitro synthesis of steroids by a feminising adrenocortical carcinoma: effect of prolactin and other protein hormones. 18 Jul 40

Alcoholic hepatitis presents as an acute hepatitis in an alcoholic. No specific laboratory tests for alcoholic hepatitis exist. Therefore, the diagnosis must be based on the clinical presentation, histology and exclusion of other causes of a similar clinical picture such as viruses and drugs. Patients with elevated bilirubin, encephalopathy and coagulopathy have a poor prognosis. Steroids, infusion of insulin and glucagon, supplementation of amino-acids and other experimental therapies do not appear to be helpful with the exception of steroids which may benefit the sickest patients. Long-term prognosis depends on the extent of cirrhotic changes present after the acute episode and on the drinking habits of the patient.
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PMID:[Alcoholic hepatitis]. 162 Dec 33

This article describes concepts of drug treatment for patients with severe renal failure (creatinine clearance less than 10 ml/min), especially in intensive care. These subjects often develop multiorgan failure and require special considerations: 1. Not only should the maintenance dose of digoxin be reduced to 0.05-0.1 mg/day, but the loading or digitalizing dose should also be diminished to 0.4-0.6 mg. 2. Penicillins, cephalosporins, quinolones, and other antibiotics with a high therapeutic ratio can be given as recommended by the manufacturer or reference lists according to renal insufficiency. 3. For drugs with a low therapeutic index, such as aminoglycosides, vancomycin, flucytosine, some antiarrhythmic agents, cardiac glycosides, and theophylline, therapeutic drug monitoring is mandatory. 4. Steroids, insulin, atropine, catecholamines, anticoagulants, thrombolytic agents, antihypertensive drugs, and organic nitrates can be given according to their effect. However, nitroprusside should be discontinued after 2 days because its metabolites may be toxic. 5. The dose of H2-receptor antagonists used for the control of gastric acidity and the treatment of peptic ulcers should be reduced to 20-50% of the normal. The administration of aluminum, magnesium, and bismuth compounds should be avoided. 6. Loop diuretics (e.g., furosemide) can be effective at increased doses in patients with chronic renal failure and fluid overload, particularly when used in combination with a thiazide in refractory edema. Thiazides alone are useless, and potassium-sparing diuretics are contraindicated. 7. Colloid-containing solutions should be infused cautiously at a maximal rate of 2 x 500 ml/week only when the plasma volume is contracted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Renal failure--concepts for drug therapy in intensive care]. 181 28

Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender-matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation.
Steroids 1991 May
PMID:The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery. 187 62

Adipose tissue is a major, nonglandular site for the aromatization of androgens to estrogens. In this tissue, the aromatase activity resides primarily in the stromal cells, and we have used cultures of stromal cells to study the effects of insulin and insulin-like growth factor I (IGF-I) on aromatase activity. Adipose tissue, obtained during indicated surgery, was digested with collagenase, and the stromal cells were isolated and cultured. Aromatase activity was determined by measuring the tritiated water (3H2O) in the medium after incubating stromal cells with [1 beta-3H]androstenedione. Insulin and IGF-I had no effect on the aromatase activity in cultured adipose stromal cells at concentrations of 10 to 1,000 microU/ml. However, insulin (100 to 1,000 microU/ml) and IGF-I (500 ng/ml) markedly attenuated the stimulatory effect of (Bu)2cAMP, but significantly augmented the dexamethasone-stimulated aromatase activity. The greater effects of IGF-I compared with the effect of insulin are compatible with both effects being mediated through the IGF-I compared with the effect of insulin are compatible with both effects being mediated through the IGF-I receptor. In addition, the effects of insulin in attenuating the aromatase activity in adipose tissue could potentiate its role in hyperandrogenic syndromes in women.
Steroids 1990 Dec
PMID:Aromatase activity in human adipose tissue stromal cells: effect of growth factors. 196 38

In a search for possible hormonal reasons for the loss of protection from myocardial infarction seen in diabetic women, serum levels of estradiol, progesterone, and luteinizing hormone were compared throughout a menstrual cycle (17 points) in eight healthy nonsmoking women and five otherwise healthy nonsmoking insulin-dependent diabetic women. The total length of the menstrual cycle and the lengths of the follicular and luteal phases did not differ between the groups. During the periovulatory and luteal phases, there was no significant intergroup difference with respect to any of the three hormones. During the follicular phase, in both groups, there was a plateau in serum progesterone concentration, with the level approximately 42% lower in the diabetic group (12.0 +/- 6.6 ng/dl versus 20.7 +/- 5.7; P less than 0.0001). Follicular-phase serum estradiol showed a rising curve in both groups; day-by-day comparison (days -10 to -3 before the luteinizing hormone peak) showed consistently higher levels in the diabetic group (mean, 108 pg/ml versus 95 pg/ml; P less than 0.001). The follicular-phase serum estradiol to progesterone ratio was nearly twice as high in the diabetic group as in the normal group (8.9 versus 4.6), a difference that was highly significant. The finding of elevated serum estradiol and subnormal serum progesterone concentrations during the follicular phase is so far unique to women with insulin-dependent diabetes mellitus. The possibility that this pronounced abnormality in diabetic women may be related to coronary disease merits testing in suitable in vivo and in vitro models of atherogenesis.
Steroids 1990 Dec
PMID:Subnormal follicular-phase serum progesterone levels and elevated follicular-phase serum estradiol levels in young women with insulin-dependent diabetes. 208 47

The effect of insulin and insulin-like growth factor-1 (IGF-1) on progesterone secretion by porcine granulosa cells and their modulatory effect on follicle-stimulating hormone (FSH)-induced responses were examined. For comparative purposes, growth hormone (GH), previously shown to stimulate IGF-1 secretion, was also included. Granulosa cells from ovarian follicles (3 to 5 mm) were cultured in multiwell plates for the first 48 hours, either in the presence or absence of 1% fetal bovine serum (FBS). Following plating, all cultures were maintained in serum-free media. The addition of only insulin, but not IGF-1 or GH, enhanced progesterone secretion under both culture conditions. When low-density lipoprotein was provided as steroid substrate, a stimulatory effect of insulin on progesterone accumulation was observed with a minimum dose of 10 ng/ml. Granulosa cells cultured in serum-free media from the time of plating secreted less progesterone and were less responsive to FSH compared with cultures plated with 1% FBS. Only insulin, but not IGF-1, enhanced FSH responses to threefold in cells cultured with 1% FBS. However, when cells were cultured in serum-free media from the time of plating, both insulin and IGF-1, but not GH, potentiated the responses to FSH, but insulin was more potent than IGF-1. Insulin-like growth-factor-1 binding studies with granulosa cells indicate the presence of specific high-affinity binding sites (Kd 3.96 nM). A dose of 100 ng/ml of insulin had negligible cross-reactivity with IGF-1 receptors.
Steroids 1990 Mar
PMID:Comparative effects of insulin and insulin-like growth factor-1 on follicle-stimulating hormone-induced responses in porcine granulosa cells. 215 94

Hyperinsulinism is associated with disorders of androgen production in humans. We have studied the effects of insulin and insulin-like growth factor-1 on androgen production in vitro using a crude preparation of mouse Leydig cells incubated with luteinizing hormone in a serum-free medium. We found a positive correlation between testosterone production and the luteinizing hormone dose over 3 hours. Exposure of the cells for 1 hour to insulin (1 micrograms/ml) prior to the addition of luteinizing hormone significantly augmented the amount of testosterone produced in response to the gonadotropin when added after this preincubation. In contrast, prior exposure of the cells to proinsulin (30 micrograms/ml), insulin-like growth factor-1 (30 ng/ml), or epidermal growth factor-1 (1 micrograms/ml) did not influence the testosterone response to luteinizing hormone. Transforming growth factor-beta reduced the testosterone response to luteinizing hormone. Transforming growth factor-beta (1,000 pg/ml) blocked the insulin augmentation of luteinizing hormone-stimulated testosterone production. We conclude that insulin has an endocrine effect on testosterone production by mouse Leydig cells in vitro. Furthermore, the Leydig cell response to insulin is itself sensitive to interaction with transforming growth factor-beta which may operate as part of the paracrine control of Leydig cell function.
Steroids 1990 Jun
PMID:Regulation of testicular function by insulin and transforming growth factor-beta. 220 Nov 4

Cellular regulation by hormones that utilize a myriad of intracellular signaling pathways is recognized to be quite complex. To investigate some of these effects in an established cell line, we tested a panel of hormones and modulators for their effects on cyclic AMP (cAMP) and progesterone production, both alone and in combination with human chorionic gonadotropin (hCG), using the MA-10 cultured Leydig tumor cell line. None significantly affected intracellular levels of cAMP, and only epidermal growth factor (EGF) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulated progesterone production. While EGF, basic fibroblast growth factor, insulin, insulin-like growth factor-1, and transforming growth factor beta all decreased cAMP production only, TPA decreased hCG-stimulated cAMP and progesterone production. Those factors that stimulated progesterone production also induced a characteristic morphological change ("rounding") of these cells. In addition, EGF, insulin, and TPA, like hCG, elevated mRNA levels of competence oncogenes (c-fos and c-myc), albeit to different extents. These data demonstrate the wide range of hormones to which the cultured Leydig tumor cell will respond, as well as the varying degree of responses observed in the intracellular signaling pathways that we examined.
Steroids 1989 Dec
PMID:Effects of hormones and intracellular mediators on differentiated functions of cultured Leydig tumor cells. 255 32

The effects of progesterone, its agonists (progestin RU-5020, glucocorticoid RU-26988) and antagonist (antiprogesterone, anti-glucocorticoid RU-486) were tested on isolated fat cells in vitro. When added to the incubation medium, all four steroids decreased basal glucose oxidation. The inhibitory effect of the steroids appeared early (20 min incubation) and was sustained during a 2-h incubation. The early inhibitory effect was less marked for progesterone agonist RU-5020 than for the other three steroids. When incubation was prolonged for 2 h, the lowest inhibitory effect was observed with progesterone antagonist RU-486. Insulin-stimulated glucose oxidation was inhibited by progesterone, its antagonist RU-486, one of its agonists RU-26988, but not by the other agonist RU-5020. Analysis of the dose response curves showed that progesterone, RU-26988, and RU-486 decreased fat cells' responsiveness and, only for RU-486, sensitivity to insulin. Adipocytes isolated from ovariectomized, progesterone-treated rats showed a decreased maximal response to insulin and decreased insulin sensitivity in opposition to cells incubated directly with the steroid. No inhibition of 125I-labeled insulin binding was seen as an acute or chronic effect of progesterone. It is concluded that progesterone and the studied related steroids decrease glucose oxidation by mechanism(s) distal to insulin binding to its specific receptors.
Steroids
PMID:Progesterone and synthetic steroids produce insulin resistance at the post-receptor level in adipocytes of female rats. 307 30


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