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G M Stancel

Publications and source records attributed to G M Stancel.

At least 73 records · Page 4Linked to original sources
PubMed1984

Hormonal control of uterine growth: alterations in luminal epithelial deoxyribonucleic acid synthesis after intraluminal application of estrogen.

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis in the uterine luminal epithelium approximately 24 h later. We previously reported that animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis measured in this cell type at 24 h. This apparent decrease in DNA synthesis is due to a shift in the time course of DNA synthesis rather than an absolute decrease in this parameter. In this report we demonstrate that this inhibitory effect of a second injection of E2 is also observed after intraluminal instillation of the hormone. This effect is dose dependent and appears to result from a shift in the time course of luminal epithelial DNA synthesis. The intraluminal instillation of E2 produces the same pattern of nuclear receptor localization as sc administration of the hormone. These results suggest that this inhibitory effect we previously described results primarily from a direct action of E2 on the luminal epithelium.

Animals↗
PubMed1983

Evidence for thyroid hormone receptors in uterine nuclei.

Nuclear preparations from the rat uterus contain specific, high affinity binding sites for T3, with the properties expected of a thyroid hormone receptor. The Kd value for the binding of T3 to these sites is 9.3 +/- 0.1 x 10(-10) M and the maximum number of binding sites is 0.11 +/- 0.02 pmoles T3 bound per mg of DNA. Competition experiments with Triac, D-T3, T4, and rT3 compared to L-T3 revealed relative affinities of 87%, 22%, 15%, and 1.6% respectively. T3 binding sites solubilized from uterine nuclear preparations by high salt extraction sediment at 3.6 S and are destroyed largely by trypsin treatment. Estradiol treatment of ovariectomized rats for 3 days did not alter the quantity of T3 binding sites expressed on the basis of DNA content. These results suggest that uterine nuclei contain a specific T3 receptor and raise the possibility that this hormone may have direct effects on the uterus.

Animals↗
PubMed1983

Effect of ovariectomy and estrogen treatment on uterine benzylamine oxidase and monoamine oxidase type A.

The activity of monoamine oxidase type A (MAO-A) of rat uteri is known to be modulated by sex steroids but no information is available with regard to benzylamine oxidase (BzAO). Thus, uterine MAO-A and BzAO activities were assayed in ovariectomized (3 weeks) and ovariectomized plus estrogen treated rats (17 beta-estradiol, 10 micrograms/kg/day, i.p. for three days). Compared with sham operated controls, MAO-A activity (total and specific) was decreased by ovariectomy and restored partially by estrogen treatment. In contrast, BzAO activity was not influenced selectively. Total BzAO activity followed changes in uterine weight such that the specific activity of BzAO, per mg tissue, was not statistically different between the three experimental groups. Although changes in the specific activity of BzAO were found on a protein and DNA basis, these changes reflect primarily alterations in protein and DNA contents and not BzAO activity. Since BzAO appears to be insensitive to direct modulation by sex steroids and may be located predominantly in uterine blood vessels, it is speculated that the enzyme may serve as a marker for hormonal influences on the vascularity and structure of the uterine vascular bed.

Animals↗
PubMed1982

The estrogenic activity of DDT: correlation of estrogenic effect with nuclear level of estrogen receptor.

Administration of o,p'-DDT to immature female rats causes a translocation of estrogen receptors to uterine nuclei which is maximum 3 hours after pesticide treatment, and a subsequent increase in uterine weight at 24 hours. A high degree of correlation (r = 0.98) exists between the level of nuclear estrogen receptor and increases in uterine weight measured 3 and 24 hours respectively after administration of o,p'-DDT, in the dose range of 10-1000 mg/kg. This high degree of correlation between these two parameters lends strong support to the hypothesis that the estrogenic effects observed following in vivo administration of o,p'-DDT result from the interaction of the pesticide with the classical estrogen receptor system.

Animals↗
PubMed1982

Hormonal control of uterine growth: temporal relationships between estrogen administration and deoxyribonucleic acid synthesis.

Administration of a single injection of estradiol (E2) causes a maximum increase in DNA synthesis of all major uterine cell types approximately 24 h later. Animals given a second injection of E2 6-12 h after the first show an apparent increase in DNA synthesis in the luminal epithelium. Animals receiving a second injection of E2 15-18 h after the first show an apparent decrease in DNA synthesis at 24 h, which is most prominent in the luminal epithelium. This apparent decrease in DNA synthesis is most apparent if the second injection of E2 is given 18 h after the first, and is due to a shift of 10-12 h in the time course of DNA synthesis rather than to an absolute decrease in this parameter. This shift in the time course of uterine DNA synthesis is a dose-dependent phenomenon and displays a dose-response curve similar to that for the stimulation of DNA synthesis by a single injection of E2. A third injection of E2, 28 h after the initial hormone treatment, again causes a shift of 10-12 h in the time course of DNA synthesis relative to that in animals receiving two injections of hormone. These results suggest that nuclear levels of estrogen receptor, which initially increase after hormone administration, must decrease before the onset of uterine DNA synthesis.

Animals↗
PubMed1982

The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding.

Long term (21-day) treatment with antidepressants induces a decrease in beta-adrenergic and serotonin 2 (5-HT2) receptor binding in rat brain frontal cortex. Since hormone imbalances are known to be associated with affective illness, the present study was undertaken to determine whether sex hormones influence these alterations in neurotransmitter receptor binding. Using receptor binding assays, we found that castration abolishes the decline in the concentration of 5-HT2, but not beta-adrenergic, receptors brought on by chronic imipramine or iprindole treatment in both male and female rats. In contrast, the receptor responses to trazodone, mianserin, and pargyline were not influenced by surgery. Furthermore, mianserin was found to reduce beta-adrenergic binding in intact females, but not males, suggesting a sex-related specificity with regard to the response to this agent. Testosterone and estrogen, but not dihydrotestosterone, reversed the effects of castration in males, suggesting that the interaction between the steroids and antidepressants is mediated through estrogenic, rather than androgenic, receptors. The results indicate that the receptor responses to some antidepressant drugs is dependent, at least in part, on the hormonal state of the animals.

Animals↗
PubMed1981

Evidence for convertible forms of soluble uterine cyclic nucleotide phosphodiesterase.

The cyclic nucleotide phosphodiesterase (3':5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) systems of many tissues show multiple physical and kinetic forms. In contrast, the soluble rat uterine phosphodiesterase exists as a single enzyme form with non-linear Lineweaver-Burk kinetics for cyclic AMP (app. Km of approx. 3 and 20 microM) and linear kinetics for cyclic GMP (app. Km of approx. 3 microM) since the two hydrolytic activities are not separated by a variety of techniques. In uterine cytosolic fractions, cyclic AMP is a non-competitive inhibitor of cyclic GMP hydrolysis (Ki approx. 32 microM). Also, cyclic GMP is a non-competitive inhibitor of cyclic AMP hydrolysis (Ki approx 16 microM) at low cyclic GMP/cyclic AMP substrate ratios. However, cyclic GMP acts as a competitive inhibitor of cyclic AMP phosphodiesterase (Ki approx 34 microM) at high cyclic GMP/cyclic AMP substrate ratios. When a single hydrolytic form of uterine phosphodiesterase, separated initially by DEAE anion-exchange chromatography, is treated with trypsin (0.5 microgram/ml for 2 min) and rechromatographed on DEAE-Sephacel, two major forms of phosphodiesterase are revealed. One form elutes at 0.3 M NaOAc- and displays anomalous kinetics for cyclic AMP hydrolysis (app. Km of 2 and 20 microM) and linear kinetics for cyclic GMP (app. Km approx. 5 microM), kinetic profiles which are similar to those of the uterine cytosolic preparations. A second form of phosphodiesterase elutes at 0.6 M NaOAc- and displays a higher apparent affinity for cyclic AMP (app. Km approx. 1.5 mu) without appreciable cyclic GMP hydrolytic activity. These data provide kinetic and structural evidence that uterine phosphodiesterase contains distinct catalytic sites for cyclic AMP and cyclic GMP. Moreover, they provide further documentation that the multiple forms of cyclic nucleotide phosphodiesterase in mammalian tissues may be conversions from a single enzyme species.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Imipramine: effect of ovarian steroids on modifications in serotonin receptor binding.

Long-term administration of imipramine caused a decrease in serotonin2 receptor binding in rat brain cerebral cortex, an effect that was abolished by ovariectomy. In contrast, ovariectomy had no effect on imipramine-induced decreases in hippocampal serotonin or in cerebral cortical and hippocampal beta-adrenergic receptor binding. Administration of estradiol or progesterone separately or in combination reestablished the effect of imipramine treatment on cortical serotonin2 receptors. These results suggest that ovarian steroids may play an important, but subtle, role in the neurochemical and perhaps clinical response to this drug.

Animals↗
PubMed1981

Most of the G1 period in hamster cells is eliminated by lengthening the S period.

Two Chinese hamster cell lines, G1+-1 and CHO, have been grown in the presence of low concentrations of hydroxyurea to determine how a slowing DNA synthesis (i.e., a lengthening of the S period) affects the length of the G1 period. Hydroxyurea concentrations of approximately 10 microM do not alter the generation times of these cell lines but do cause increases in S with corresponding decreases in G1. In both cell lines, 10 microM hydroxyurea reduces G1 to an absolute value of 1 hr, which represents decreases of 70% (G1+-1) and 60% (CHO) from control values. Higher concentrations of hydroxyurea increase the generation times and lengths of S for both cell lines but do not reduce G1 below the minimum value of 1 hr. These observations indicate that the majority of G1 is expendable and most of G1 therefore cannot contain specific events required for the initiation of DNA synthesis. This result supports the hypothesis that G1 is a portion of the cell growth cycle but not of the chromosome cycle.

Animals↗
PubMed1981

Hormonal control of uterine growth: the effect of hypothyroidism on estrogen-stimulated cell division.

The increase in mitotic indices of uterine luminal epithelium, stroma, and myometrium were determined as a function of time after the administration of a single dose of 17 beta-estradiol to euthyroid and hypothyroid rats. Hypothyroidism reduced the increase in the mitotic index 5-fold in the luminal epithelium, 6-fold in the stroma, and 9-fold in the myometrium. In addition to reducing mitotic indices, hypothyroidism also produced a shift of 12 h in the time course of estrogen-stimulated cell division of all uterine cell types relative to euthyroid animals. This shift in the time course of cell division was preceded by a shift in the time course of uterine DNA synthesis measured by tritiated thymidine incorporation. In contrast, hypothyroidism did not alter the magnitude or the time course of synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose after estrogenic stimulation. These results indicate that hypothyroidism decreases the ability of all major uterine cell types to undergo cell division in response to acute administration of estradiol, and also shifts the time course of the uterine growth response to the hormone.

Animals↗
PubMed1981

Decreased cell division of the uterine luminal epithelium of diabetic rats in response to 17 beta-estradiol.

The uterine growth response to estradiol as determined by luminal epithelial cell division was measured in euglycemic and drug induced insulin deficient rats. The results demonstrated that uterine cell division in insulin deficient rats is depressed when compared to euglycemic rats. Replacement of insulin by osmotic minipumps (Alza Corporation) in insulin deficient rats restored the level of luminal cell division to those observed in euglycemic rats.

Animals↗
PubMed1981

Stimulatory and inhibitory effects of estrogen and antiestrogen on uterine cell division.

Acute administration of 17 beta-estradiol or the antiestrogen nafoxidine to immature rats produces quantitatively similar responses in the uterine stroma and myometrium, although the responses to nafoxidine occur at slightly later times. Both the hormone and drug cause nuclear translocation of equivalent amounts of estrogen receptor in these two cell types, although receptor translocation is slower with nafoxidine, and nuclear receptor levels remain elevated for an extended time. Based upon labeling and mitotic indices, however, the response of the luminal epithelium to a maximum dose of nafoxidine is much lower than that produced by estradiol, although nafoxidine treatment causes massive hypertrophy of luminal epithelial cells and causes nuclear translocation of estrogen receptors in this cell type. If nafoxidine is administered 30 min after administration of estradiol, cell division in the luminal epithelium is inhibited. Furthermore, multiple injections of estradiol itself within a 24-h period decrease cell division in the luminal epithelium relative to controls receiving a single injection of the hormone. These results indicate that estradiol and the antiestrogen can have both inhibitory and stimulatory effects on the luminal epithelium and that cell division in different uterine cell types can be differentially affected.

Animals↗
PubMed1978

Activation of mammalian cyclic AMP phosphodiesterases by trypsin.

BHK fibroblasts contain two forms of cyclic AMP phosphodiesterase 3':5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) as analyzed by linear sucrose gradient fractionation; a 3.6-S form (peak I) and a 6.7-S form (peak II). Peak I is specific for cyclic AMP as substrate and displays Michaelis-Menten kinetics with an apparent Km of 2--3 micrometer. Peak II hydrolyzes cyclic GMP and displays anomalous kinetics for cyclic AMP hydrolysis. The activity of isolated peak II for cyclic AMP is increased by storage at 4 degrees C, treatment with trypsin, or treatment with rat brain and BHK fibroblast activator proteins. The activity of isolated peak I is unaffected by these conditions. Linear sucrose gradient fractionation demonstrates that activation of peak II by trypsin leads to the formation of a 3.6-S cyclic AMP-specific enzyme form, possibly peak I. In contrast to BHK fibroblasts (and most other mammalian tissues), rat uterus contains only one form of cyclic nucleotide phosphodiesterase on linear sucrose gradients, a 7-S form capable of hydrolyzing both cyclic AMP and cyclic GMP. Treatment of rat uterine supernatant with trypsin leads to the appearance of a 4-S, cyclic AMP-specific form with properties similar to that of BHK peak I. These data suggest that the kinetically complex, higher molecular weight cyclic nucleotide phosphodiesterases may consist of more than one catalytically active site and that multiple forms of the enzyme arise through dissociative mechanisms, possibly as a means of in vivo regulation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Characterization of soluble uterine cyclic nucleotide phosphodiesterase.

Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP.

3',5'-Cyclic-AMP Phosphodiesterases↗