Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Human mammary ducts were maintained in median-term organ culture. DNA synthesis was assessed by the uptake of 3H-thymidine in epithelial cells; labeling indices were counted on autoradiographies. DNA synthesis grossly remained between starting values in the basic conditions without hormones. Insulin (5 microgram/ml) did not stimulate the uptake of the isotope as compared with the controls. Estradiol (0.001 microgram/ml) and progesterone (1 microgram/ml) highly significantly enhanced DNA synthesis; subsequent waves did occur.
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PMID:Effect of hormone on human mammary duct in vitro. 68 Jun 31

The effect of various hormones or hormone combinations on DNA synthesis was investigated in organ cultures of 20 dimethylbenz(a)anthracene-induced rat mammary tumors. Three tumors were insulin independent and were totally insensitive to all other hormones tested. Seventeen tumors were insulin dependent for DNA synthesis and, in the presence of insulin, displayed variable responses to the other hormones. Nine of 12 such tumors were significantly stimulated by the combination of prolactin and progesterone. Given alone, these hormones were effective in only 25% of the tumors tested. Estradiol used at 2 dose levels, 0.001 or 1.0 mug/ml, acted in a reverse manner to progesterone and proved inhibitory in combination with prolactin in 40% of cases. It was ineffective alone except in 1 of 10 cases in which a stimulatory effect was recorded. A comparison in 4 tumors between estimation of DNA synthesis ([3H]thymidine incorporation into DNA) and colchicine-blocked mitoses demonstrated a good concordance. These results are discussed in terms of variations in the degree of hormone responsiveness of individual tumors and of the known hormone-dependent properties of the 7,12-dimethylbenz(a)-anthracene tumors in vivo.
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PMID:Effects on insulin, prolactin, progesterone, and estradiol on DNA synthesis in organ culture of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. 81 26

Organ cultures of liver from untreated male Xenopus respond to 17 beta-estradiol in the culture medium by synthesizing and secreting the yolk protein precursor vitellogenin. Vitellogenin synthesis, as a primary response, is first detectable on the fourth day of culture, and comprises up to 12% of the protein synthesized on the eighth day. Estradiol is required during the lag period of 4 days. Tissue from male Xenopus injected with 1 mg of estradiol 30 days before the start of culture responds more rapidly and to a greater extent to estradiol in the medium than tissue from uninjected males. During such a secondary response, vitellogenin is first detectable in the medium on the second day of culture, and becomes up to 24% of the protein synthesized on day 6. The rate of amino acid incorporation into total protein also increases in response to estradiol, but the rate of synthesis of albumin decreases rapidly in culture whether or not estradiol is present, in both the primary and secondary responses. A maximal response is seen with 10(-8) M estradiol. Progesterone, testosterone, dexamethasone, and insulin neither induce vitellogenin synthesis in culture nor modify the response to estradiol. DNA synthesis inhibitors do not prevent the response to estradiol in vitro, suggesting that cell division is not required for the initial response leading to vitellogenin synthesis.
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PMID:Direct induction by estradiol on vitellogenin synthesis in organ cultures of male Xenopus laevis liver. 94 40

To evaluate the effect of contraceptive steroids on endogenous glucagon and insulin secretion, theta-arginine was infused intravenously in normal young women before and during selective steroid treatment. The effect of the combination of an estrogen derivative (mestranol), plus norethindrone (Norinyl, Syntex) was compared to the effect of ethinyl estradiol alone and to norethindrone alone. All three steroid schedules resulted in suppression of aminogenic insulin secretion. However, glucagon secretion was reduced only with ethinyl estradiol alone or the combination of mestranol plus norethindrone. In accordance with previous reports, treatment with an ethinyl estradiol derivative alone or in combination with norethindrone resulted in a tendency for elevated serum lipid concentration, while norethindrone alone resulted in a significant reduction in serum lipid concentration. These observations suggest an inverse relationship between aminogenic glucagon secretion and serum lipid concentration as influenced by contraceptive steroids. It is suggested that the metabolic effects of these steroids may be mediated in part by the associated alterations in pancreatic hormone secretory capacity.
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PMID:Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women: I-Lipid physiology. 115 75

Data are reported from the combined results of two studies assessing the lipid and carbohydrate effects of a triphasic preparation of norgestimate and ethinyl estradiol (Ortho TriCyclen, Tri-Cilest) over a 2-year period in 1,783 healthy women. Mean values for serum levels of high-density lipoprotein cholesterol (HDL-C) were increased significantly, with a percent change at 24 months of 13.2. Values for the ratio of low-density lipoprotein cholesterol to HDL-C were reduced throughout the study period (mean change of -6.4% at cycle 24). There were no clinically significant changes in fasting blood glucose levels or insulin levels or in values for glycosylated hemoglobin. These results are consistent with those of previous studies and indicate that the triphasic preparation of norgestimate and etinyl estradiol is a selective and minimally androgenic oral contraceptive agent. Long-term therapeutic benefit may accrue from the favorable influences on the lipid profile.
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PMID:Lipid and carbohydrate effects of a new triphasic oral contraceptive containing norgestimate. 132 56

12 healthy volunteers attending the family planning clinic at Shanghai, First Maternity and Infant China, Hospital, enrolled in the study, Oral contraceptives (OCs) were prescribed: Marvelon (150 mcg of desogestrel--DSG), Mercilon (150 mcg of DSG), and Microgynon (150 mcg of levonorgestrel--LNG). The patients were divided into 6 groups of 2 persons each in a randomized cross-over study. OCs were taken on day 6 of the cycle up to day 21, then stopping for 7 days. Each OC was used for 3 months. During the pretreatment cycle between days 6 and 9 of the follicular phase and 21 and 22 of the luteal phase a blood sample was taken after fasting for determination of lipids, sex hormone binding globulin (SHGB), ceruloplasmin, and testosterone. After glucose loading, significant increases of glucose and insulin occurred at 1, 2, and 3 hours during treatment with Microgynon only. The ratio for total areas of insulin to glucose did not change significantly nor did glycosilated hemoglobin A1 levels. Serum triglyceride concentrations increased significantly for both Marvelon (27%-43%) and Mercilon (29-40%). Serum high density lipoprotein (HDL) cholesterol concentrations were significantly elevated with Marvelon but less so with Mercilon, while HDL-C decreased significantly with Microgynon. The serum low density lipoprotein (LDL) cholesterol changes were not significant, but LDL-C concentrations declined with DSG formulations and increased with Microgynon. Apoprotein A1 and A2 increased significantly for both Marvelon and Mercilon. Apoprotein A2 increased with Microgynon. Serum SHBG increased markedly with Marvelon (335-380%). Serum testosterone concentrations decreased significantly (33.2-40.4% with Microgynon) and so did ceruloplasmin values. The antiestrogenic effect of strong LNG in Microgynon produced significant metabolic changes. The effect of 30 mcg EE in Marvelon and 20 mcg EE of Mercilon was equal.
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PMID:A cross-over study of three oral contraceptives containing ethinyloestradiol and either desogestrel or levonorgestrel. 153 80

A large biracial cross-section of 1038 healthy children aged 6-18 yr with 519 blacks, 519 whites, 678 males, and 360 females was evaluated for Tanner stage and serum levels of androstenedione, dehydroepiandrosterone-sulfate, estradiol, progesterone, and testosterone. The anthropometric values of the blacks and whites were very similar at each Tanner stage with only minor differences in age, height, and weight related to an earlier onset of puberty in blacks. The hormones dehydroepiandrosterone-sulfate, progesterone, and testosterone did not exhibit any racial differences. Estradiol showed a significantly higher level among black males compared to white males (P less than or equal to 0.05) whereas androstenedione was significantly higher in both white males (P = 0.0001) and females (P less than or equal to 0.01) compared with blacks. Many hormones are known to effect insulin resistance and others have reported a correlation between insulin levels and androstenedione. Blacks suffer disproportionately from diabetes. Since puberty is a time of dramatic changes in insulin resistance, racial (black-white) differences in steroid hormone changes were explored. This study shows that a racial difference in androstenedione levels exist during puberty, at a time when racial differences in insulin resistance are becoming manifest.
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PMID:Steroid hormones during puberty: racial (black-white) differences in androstenedione and estradiol--the Bogalusa Heart Study. 163 61

The nuclear estrogen receptor was characterised in isolated rat adipocytes. The binding reaction with [3H]estradiol was performed with intact isolated rat adipocytes and the radioactivity associated with the nucleus was subsequently determined after cell lysis. The nuclear uptake of [3H]estrogen in rat adipocytes was temperature dependent and steroid specific. The steady-state binding was achieved after 30 min at 37 degrees C and was constant for several hours. Estradiol was found to bind to a homogeneous class of nuclear receptors in epididymal adipocytes with an apparent Kd of 3.1 +/- 0.76 nM and a Bmax of 7.98 +/- 1.11 fmol/10(6) cells corresponding to about 4800 receptors per nucleus. The estradiol binding exhibited regional variations in isolated adipocytes. In lean rats the highest receptor number was found in epididymal adipocytes, whereas there was a significantly lower number of nuclear binding sites in perirenal and subcutaneous adipocytes (P less than 0.05), unlike in older and more obese rats where the nuclear estradiol binding was greatest in adipocytes from the perirenal fat depot. Incubations with isoproterenol (10 microM) and dibutyryl-cAMP (2.5 mM) both reduced estradiol binding by 56% (P less than 0.005), while insulin (1 nM) enhanced the estradiol binding by 37% (P less than 0.01). In conclusion, a specific and high affinity nuclear estradiol receptor was demonstrated in rat adipocytes and regional differences in nuclear estradiol binding were detected. Furthermore, it was demonstrated that nuclear estradiol binding could be modulated by other agents known to affect adipocyte metabolism.
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PMID:Nuclear estradiol binding in rat adipocytes. Regional variations and regulatory influences of hormones. 164 50

Of the contraceptive choices open to a post-partum woman with gestational diabetes, this discussion concentrates on low-dose oral contraceptives. Although gestational diabetes usually clears at delivery, 75% of these women will go on to developed impaired glucose tolerance or overt diabetes, especially if they are obese or if their glucose level had been high. Many elect permanent sterilization, but those requiring reversible contraception usually choose the IUD or the pill. IUDs carry a high risk of infection and are less effective in diabetics. The author compared a low-dose combined pill with 400 mcg norethindrone and 35 mcg ethinyl estradiol (Ovcon 35), and a pill containing levonorgestrel (Triphasil), to barrier contraception in 230 women with recent gestational diabetes. After 6-13 months of use 11-17% of each group had impaired glucose tolerance, and 15-20% of each group had diabetes (n.s.). Insulin levels rose from 28.5 mIU/mL to 59.7 in controls, 32.0 to 71.8 in Ovcon 35 users, and from 40.2 to 85.1 in Triphasil users (p0.05). HDL values rose significantly in the group taking Ovcon, and LDL values fell significantly in all 3 groups. These low-dose pills can be used safely in postpartum gestational diabetic women, as long as they do not smoke, are encouraged to lose weight, and have no sign of cardiovascular disease as evidenced by albuminuria and an ophthalmoscopic exam.
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PMID:Contraceptive options for the gestational diabetic woman. 167 21


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