Search PubMed⌕ Search

Biomedical subjects

G M Stancel

Publications and source records attributed to G M Stancel.

84 records · Page 5Linked to original sources
PubMed1978

Regulation of the uterine response to estrogen by thyroid hormone.

After estradiol (E2) administration, early increases (within 4 h) in uterine wet weight and the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose are similar in ovariectomized rats and in ovariectomized rats made hypothyroid by feeding a low iodine diet containing prophylthiouracil. Most late uterine responses occurring 24 h after E2 treatment, however, are greatly diminished in the hypothyroid animals. The diminished responses include increases in uterine wet weight, dry weight, protein content, RNA content, and the incorporation of thymidine into uterine DNA. One response, the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose is not diminished in hypothyroid rats 24 h after E2 treatment. The diminished uterine response is not due to a shift in the dose-response curve for E2, but results from a decrease in the magnitude of the maximum uterine response. Treatment of hypothyroid rats with exogenous T3 restores the diminished uterine response in a dose-dependent and time-dependent manner. A dose of 0.5 microgram T3/100 g BW for 5 days restores the response completely, while 48-72 h of treatment with higher doses of T3 are required to restore the response. The effect of T3 is not mediated by the pituitary, since exogenous T3 restores diminished uterine responses in ovariectomized, hypophysectomized animals. These results suggest that thyroid hormones may have a direct effect on the uterus which regulates the responsiveness of the organ to E2.

Animals↗
PubMed1978

Selective blockade of estrogen-induced uterine responses by the antiestrogen nafoxidine.

The response of the immature rat uterus to the antiestrogen, nafoxidine (Upjohn U-11, 100A), is maximum at a dose of 5 micrograms. This dose of nafoxidine sustains the uterine response for at least 72 h. After treatment with 5 micrograms nafoxidine for 24 h, uterine cytosol contains approximately one half the total number of estrogen receptors originally present in uteri of untreated animals, and uterine nuclei also contain approximately one half the receptors originally present in unstimulated tissue. The total amount of uterine estrogen receptor, however, is not altered 24 h after treatment with nafoxidine relative to saline-treated controls, while estradiol treatment doubles the total amount of receptor relative to controls. Pretreatment with 5 micrograms nafoxidine for 24 h does not block the uterine response occurring 4 h after the subsequent administration of estradiol, but does block the uterine response occurring 24 h after the subsequent administration of estradiol. These results suggest that uterine nuclei contain different acceptor sites for regulating short term and long term uterine responses to estrogen.

Animals↗
PubMed1977

Hormonal control of transcription in the rat uterus. Stimulation of deoxyribonucleic acid-dependent RNA polymerase III by estradiol.

DNA-dependent RNA polymerases were extracted from rat uterine tissue, partially purified and resolved by DEAE-Sephadex chromatography. RNA polymerases I, II, IIIA, and IIIB eluted at the characteristic ammonium sulfate concentrations of 0.15, 0.28, 0.34, and 0.42 M, respectively. The sensitivity of each peak of polymerase to alpha-amanitin was examined and was shown to be essentially identical to the three classes of RNA polymerases in other mammalian systems. RNA polymerase I was insensitive to high levels of alpha-amanitin, RNA polymerase II was sensitive to low concentrations of alpha-amanitin (50% inhibition at 0.006 mug/ml) and RNA polymerases IIIA and IIIB were sensitive to high concentrations of alpha-amanitin (50% inhibition at 18 mug/ml). The alpha-amanitin sensitivity curve of total RNA synthesis measured in isolated nucleo demonstrated that the activity of each class of RNA polymerase could be quantitated in uterine nuclei. Thus the initial decrease in activity at low concentrations of alpha-amanitin (50% inhibition at 0.005 mug/ml) was attributed to the inhibition of RNA polymerase II activity, the second decrease in activity at higher concentrations of alpha-amanitin (50% inhibition at 15 mug/ml) was attributed to the inhibition of RNA polymerase III activity, and the activity which was resistant to the highest alpha-amanitin concentration tested was attributed to RNA polymerase I activity. When estradiol was given to immature rats 6 h before killing both RNA polymerases I and III levels in nuclei were increased significantly over the control values. The time course of these changes demonstrated that the increases in RNA polymerases I and III were first evident between 1.5 and 3 h following hormone treatment. Significantly, these increases in polymerase I and III in nuclei parallel the published increases for rRNA and tRNA synthesis following hormone treatment. However, the amount of RNA polymerase I and III was not altered upon extraction, suggesting that these changes are due to the alteration in chromatin template activity. Both estradiol and estriol produced identical increases in uterine RNA polymerase I and III 6 h after treatment.

Amanitins↗
PubMed1976

Estrogen receptors in the rat uterus. Retention of hormone-receptor complexes.

The retention pattern and biochemical characteristics of estrogen receptors in the nuclei of uterine cells were studied as a function of time after the in vivo injection of estradiol (E2) to immature female rats. One hour after the injection of 0.1 mug of tritiated E2, approximately 0.20 pmol per uterus of receptor bound hormone is retained in uterine nuclei. This dose of E2 produces a maximal uterotrophic response. Six hours after E2 administration, uterine nuclei retain 0.04-0.08 pmol of hormone per uterus. Hormone receptor complexes extracted from uterine nuclei 1, 3, and 6 h after in vivo injection of hormone have similar structural and binding characteristics. Receptors extracted at all three times sediment at 5S in high salt gradients and have a dissociation binding constant of approximately 3 nM for E2. The wash-out curves of receptors as a function of salt concentration are identical for uterine nuclei from animals treated for 1 or 6 h with estradiol, suggesting that the nature of the nuclear binding of receptors is not altered during this time interval. Experiments utilizing the injection of unlabeled estradiol, followed by an in vitro exchange procedure with tritiated estradiol, indicated that the total nuclear estrogen receptor sites, i.e., filled and vacant, decreased similarly.

Animals↗
PubMed1975

Cyclic nucleotide phosphodiesterases in uterine development.

Activities of cyclic nucleotide phosphodiesterase were studied in rat uterus as a function of age, DNA and protein content. Linear kinetics were observed for uterine homogenate cyclic GMP (cGMP) phosphodiesterase activity, but anomalous double-reciprocal plots, suggestive of multiple enzyme forms, were observed for cyclic AMP (cAMP) hydrolysis, cAMP phosphodiesterase was therefore measured at high and low substrate concentrations, 200 muM and 0.25 muM cAMP, respectively, to approximate multiple enzyme activities. Based upon total organ content, the total cAMP and cGMP phosphodiesterase activities increased throughout uterine development, from 5-50 days of age. On the same basis, the apparent low KM cAMP phosphodiesterase increased only between days 5 and 15 and showed no significant increase between days 15 and 50. On the other hand, specific activities of an apparent low KM cAMP phosphodiesterase, expressed per mg of protein or per mug of DNA, showed a marked reduction in activity between 30 and 50 days of age. Chronic administration of 17beta-estradiol to immature rats increased their uterine protein content and decreased the specific activity of the apparent low KM cAMP phosphodiesterase. In another estrogen target tissue, the anterior pituitary, protein and DNA content also increased during development but no changes in specific activities of cyclic nucleotide phosphodiesterase were noted. These results suggest the possible participation of cyclic nucleotide phosphodiesterases in the induction of uterine growth and development by ovarian hormones.

3',5'-Cyclic-AMP Phosphodiesterases↗