Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin and estrogen binding have been determined in 7,12-dimethylbenz(a)anthracene-induced mammary tumors of rats in various endocrine states. Hormonal therapy, such as diabetes and ovariectomy, resulted in differential effects on growth patterns and hormone binding of tumors coexisting in the same host or in different hosts. It was observed that tumors that continued to grow after the host was made diabetic (insulin independent) or started to regress after ovariectomy (ovarian dependent) demonstrated decreased insulin binding. Tumors that regressed in diabetic hosts (insulin dependent) or continued to grow in ovariectomized animals (ovarian independent) showed an increased insulin-binding capacity. No significant change in insulin binding was observed in tumors that remained static after ovariectomy or induction of diabetes. Estrogen binding in tumor cells from diabetic rats paralleled the pattern of tumor growth response to diabetes; insulin-independent tumors demonstrated a significant increase in binding compared to tumors from intact hosts, and insulin-dependent tumors showed decreased estrogen receptor levels. From these results, we conclude that (a) insulin plays a positive role in regulating estrogen-binding capacity, (b) ovarian hormones may play a role in regulating insulin-binding capacity, and (c) a relationship between insulin and ovarian hormones and the growth of 7,12-dimethylbenz(a)anthracene-induced tumors is strongly suggested and may have therapeutic implications.
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PMID:Relationship between insulin and estrogen binding to growth response in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. 41 34

It has been proposed that a nonsteroidal hormone such as insulin may directly exert an influence through estrogen receptors and alter the biologic behavior of steroid hormone target tissue. The implication of such a proposal is that diabetes may alter the outcome of estrogen receptor-positive tumors such as breast or endometrial carcinomas. To evaluate the effect of insulin on a receptor-positive tumor, we examined the direct effect of insulin on an estrogen receptor and its subsequent biologic effect on a receptor-positive endometrial carcinoma model in vitro and in vivo. An in vitro experiment demonstrated that when the estrogen receptor-positive cell line was grown in serum-free media with low insulin, there was a loss of intracellular receptors for estrogen. This loss of estrogen receptors was also associated with increased growth rate as reflected by increased thymidine uptake. Similarly, in vivo experiments demonstrated that a diabetic host with a high blood glucose level and a low insulin level exhibited development of growth of a receptor-negative tumor with accelerated growth rate in contrast to growth of a receptor-positive tumor with slower growth rate in a normal host with normal serum insulin and blood glucose levels. Data suggest that insulin may modulate the growth of estrogen receptor-positive tumors through its direct effect on estrogen receptors.
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PMID:Modulation of estrogen receptor by insulin and its biologic significance. 294 76

We have studied the cytosolic estrogen receptor in uterus of rats after castration and diabetes induction with Streptozotocin, and the relationship of estradiol (E2) binding with phosphatase activities. Ovariectomy (OVX) and diabetes produced a significant reduction in Type I and II binding sites, but did not affect the equilibrium dissociation constants. The reduction of receptor levels was partially reversed by homogenization and incubation with 20 mM molybdate (MoO4) and also by chronic treatment with E2. Considering the possibility that the increase in E2 binding in the presence of MoO=4 was due to phosphatase inhibition, the activities of these enzymes hypothetically involved in receptor dephosphorylation and inactivation were determined in uterine homogenate and cytosol from intact, OVX, and diabetic rats with and without E2 treatment. Chronic OVX and diabetes induced stimulation of alkaline, acid and neutral phosphatase activities. On the contrary, the increment of estrogenic receptors due to E2 treatment was not correlated with changes in phosphatase activity. It is possible that this effect was due to the protection of the receptor or to the induction of receptor synthesis by E2. Molybdate inhibited acid and neutral phosphatases and increased alkaline phosphatase, which suggest that neutral and acid phosphatases are identical and that they were responsible for the receptor inactivation. However, it is unclear at present the relationship between the increment of alkaline phosphatase and the reduction of receptors.
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PMID:Estradiol binding and phosphatase activity in the uterus after castration and chronic diabetes: effect of molybdate and estrogen replacement. 300 2

We have previously shown that there are decreases in the sex differences seen in certain hepatic drug and steroid metabolising enzymes in rats with early (4 day) streptozotocin-induced diabetes. We postulated that hepatic sex hormone receptors or binding proteins might be involved in modulation of the sex differences noted in metabolism. In the present study, we measured the binding kinetics of the hepatic cytosolic estrogen receptor and androgen receptor, along with the high capacity-low affinity estrogen binding protein. At 4 or 10 days post-streptozotocin (60 mg/kg intravenously), there was no change in the maximum binding capacity of the estrogen receptor, nor in the hormone affinity of any of the three proteins. However, the binding capacity of the androgen receptor and estrogen binding protein in the diabetic animals was decreased to less than half of control levels. This effect could not be reversed by hormone replacement with any of the following regimens: protamine zinc insulin, 10 U/kg subcutaneously once a day; Toronto insulin, 15 U/kg subcutaneously twice a day; testosterone enanthate, 1 mg/kg s.c. once a day; triiodothyronine, 30 micrograms/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 micrograms s.c. 7 times daily, 30 micrograms i.v. 4 times daily; or various combinations of these hormones. Stress, such as 4 intravenous injections of saline per day, was noted to decrease the binding capacity of the estrogen binding protein. Therefore, we measured the basal serum corticosterone levels, which were not significantly different from control values in untreated or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic estrogen and androgen receptors and binding proteins in streptozotocin-diabetic male Wistar rats. 332 27

The present study examined the effects of streptozotocin-induced diabetes on prolactin (Prl) secretion and its correlation with estrogen receptor levels in the anterior pituitary and hypothalamus. Prl was measured in adult ovariectomized rats and after estradiol treatment (10 micrograms estradiol benzoate (Eb) 48, 24 and 1 h before experiments) or acute TRH administration (4 micrograms/kg body weight). Substantial decreases in estradiol- and TRH-induced Prl release were observed in diabetic rats. Insulin therapy was able to restore this response. Measurement of nuclear estradiol receptors by exchange assay in the pituitary of Eb-treated rats revealed a significant reduction in receptor levels in the diabetic group and a restoration to normal values in insulin-treated diabetic rats. Similar results were obtained by measuring total pituitary receptor content (cytosolic plus nuclear receptors). No significant changes were observed in nuclear hypothalamic estradiol receptors. However, the number of total hypothalamic estradiol receptors was diminished in diabetic rats although the translocation was proportionally greater in these animals. These results indicate that the disrupted reproductive functions described in streptozotocin diabetic rats may be due, at least in part, to deficiencies in Prl secretion and pituitary estradiol action.
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PMID:Alterations in the prolactin secretion in streptozotocin-induced diabetic rats. Correlation with pituitary and hypothalamus estradiol receptors. 393 99

The relationship of clinically defined menstrual categories and an independent measure of hormonal stimulation, maturation index of vaginal smear cytology, was studied. Analysis of 596 smears obtained at the time of breast cancer diagnosis revealed a statistically significant association between menstrual status and maturation index. However, within each menstrual group varying levels of maturation were noted. Estrogenic effect in the absence of exogenous hormone administration was found in 11% of patients following bilateral oophorectomy and among 24% of women whose natural menopause occurred 20 years or longer prior to diagnosis. Endogenous estrogen production appears to continue for many years among some women. Clinical factors such as obesity, diabetes and/or hypertension may stimulate high squamous maturation in some patients. Others of the same age and with similar clinical histories were found to have atrophic smears. The differences in maturation index may be due to individual variations in: endogenous hormone levels; sensitivity of the vaginal mucosa to similar hormonal stimuli; use of certain medications; or unidentified exogenous factors. The maturation index was found to be significantly associated with the following prognostic factors: weight relative to height, tumor size and estrogen receptor content of the primary tumor. These findings indicate that vaginal smear cytology may define specific subsets within menstrual categories which may be relevant to therapy and prognosis in breast cancer.
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PMID:Association of vaginal smear cytology with menstrual status in breast cancer. 402 97

The effects of relatively short- or long-term diabetes on sexual receptivity and and proceptivity and on hypothalamic estrogen and progestin receptors were examined in rats fed regular chow or high fat diet. Ovariectomized, streptozotocin-induced chronically insulin deficient and normal rats received sequential treatments with 2 micrograms estradiol benzoate (EB) and 1 mg progesterone (P) 10 days following the induction of diabetes and were tested for lordosis and soliciting behaviors. Nondiabetic rats fed either diet displayed significantly higher lordosis and solicitation behaviors than chow-fed diabetics, and fat-fed diabetic animals displayed behavior levels intermediate to those of nondiabetic and chow-fed rats. Ten days after the induction of diabetes, the levels of hypothalamic estrogen receptors of chow-fed diabetics were significantly lower than nondiabetics with the fat-fed diabetic group showing intermediate levels. However, 70 days after streptozotocin treatment diabetic rats had significantly lower estrogen receptors than nondiabetics regardless of the diet. Treatment of long-term (70 days) diabetic rats with 1-2 U of U-100 Lente insulin for 24 hr or 7 days was ineffective in restoring the hypothalamic estrogen receptor concentrations to those of nondiabetics. Three weeks following induction of diabetes, induction of cytoplasmic progestin receptors by EB treatment was significantly impaired in diabetic animals fed either chow or high fat diet. Although the reproductive dysfunctions present in short-term diabetic female rats may be due in part to chronic fuel deprivation, it appears that the long-term maintenance of cytosol estrogen receptor level is dependent on other actions of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Copulatory behavior and hypothalamic estrogen and progestin receptors in chronically insulin-deficient female rats. 635 84

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.
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PMID:Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver. 659 5

Perinatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. The dynamics of the induction of estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2) was examined in the uterus and vagina of neonatally DES-exposed and -unexposed ovariectomized adult mice. In the uterus of neonatally DES-unexposed ovariectomized mice, the expression of ER mRNA increased within 1 h after E2 administration and declined by 12 h thereafter. ER mRNA in the vagina decreased within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus, c-jun and c-fos mRNAs increased in concentration within 1 h after E2 administration, showing a peak 3 h after the stimulation; they decreased with time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs increased rapidly, reaching a peak within 1 h after the stimulation. However, the expression of c-myc in uterus and vagina was not changed by postpuberal E2. These results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the vagina differs from those in the uterus. In the neonatally DES-exposed ovariectomized adult mice, uterine ER mRNA expression levels were significantly higher than in the unexposed ovariectomized controls; however, vaginal levels were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18- and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally DES-exposed ovariectomized mice were not further altered by post-puberal E2 and may be related to ovary-independent persistent changes in the genital tract.
Exp Clin Endocrinol Diabetes 1996
PMID:Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without post-puberal estrogen administration. 874 Sep 34

In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.
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PMID:Control of fertility by metabolic cues. 925 2


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