Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Promegestone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1982

Estradiol and progesterone binding components in the cytosol of normal human fallopian tubes.

The in vitro binding of labeled estradiol and R5020 to receptor proteins from human fallopian tube cytoplasmic fractions has been studied. Both compounds give rise to two separate peaks in density gradient analysis experiments under low ionic strength conditions: a "8 S" steroid-hormone-specific peak and a "4 S" peak accounted for by non-specific binding. The receptor molecules were further characterized by a competition studies, electrophoretic technique and gel chromatography. The receptor content for both steroid hormones varied throughout the menstrual cycle. The estradiol and progesterone receptor concentration were highest during the proliferative phase and were very significantly lower in the second half of the menstrual cycle. Furthermore measurement of both receptors in the cytosol revealed differences among the anatomical segments of the fallopian tube. The highest estradiol and progesterone binding could be detected in the ampullary region, significantly lower levels of estradiol and progesterone receptor were seen in the infundibulum and the isthmus.

Binding, Competitive↗
PubMed1982

Interactions of antiglucocorticoids with glucocorticoid receptors.

Six known or potential antiglucocorticoids were used as steroid probes in a competitive binding assay to elucidate the binding specificity of the agonist sites of four different rat glucocorticoid receptors. The object was to determine whether the binding of this class of steroids was particularly sensitive to subtle differences between these sites. Cytosolic extracts of heart, pancreas, kidney and liver were evaluated. The order of competitive potency for the first three preparations was found to be medroxyprogesterone greater than deoxycorticosterone greater than progesterone greater than R-5020 greater than cortexolone greater than 17-hydroxyprogesterone. The order for the glucocorticoid receptor of liver, on the other hand, was R-5020 greater than progesterone greater than deoxycorticosterone greater than medroxyprogesterone greater than cortexolone greater than 17-hydroxyprogesterone. Although this partial reversal of specificity could reflect a difference in the agonist site of the liver receptor, mixing experiments, in which cytosolic extracts of liver were incubated with kidney cytosol extracts, demonstrated that the liver cytosol contained an additional factor that could change the apparent specificity of the kidney glucocorticoid receptor. This factor was stable at 0 degrees C for at least 18 h, heat-labile and non-dialyzable. These results suggest that the liver receptor's specificity may actually be the same as the other three, but appears to be different in this type of assay because of this additional factor. It is similar that their agonist sites are most likely identical.

Animals↗
PubMed1983

Differential antiestrogen action in the immature rat uterus: a comparison of hydroxylated antiestrogens with high affinity for the estrogen receptor.

The non-steroidal antiestrogens LY117018 and monohydroxytamoxifen are partial agonists in the 3-day immature rat uterine weight test. Both compounds stimulated increases in uterine progesterone receptor concentration (as determined by DCC assay and SDG analysis) and luminal epithelial cell height. However, LY117018 was much less estrogenic than monohydroxytamoxifen. The study also showed that the antiestrogenic effects of LY117018 and monohydroxytamoxifen could be reversed in vivo by increasing doses of estradiol. The partial uterotrophic effect of monohydroxytamoxifen and full uterotrophic effects of estradiol were both inhibited by high doses of LY117018 at an approximate dosage ratio of 1:24, w/w. This result suggests a common mechanism for the action of estradiol and the hydroxylated antiestrogens. Since LY117018 reversed the binding of [3H]estradiol and estrogen-competable [3H]monohydroxytamoxifen binding in the rat uterus in vivo, the effects of nonsteroidal antiestrogens on gross uterine wet weight can be explained by competitive interaction with estradiol via the estrogen receptor mechanism. However, the weakly estrogenic antiestrogen LY117018 was unable to inhibit estrogen-stimulated rises in luminal epithelium cell height and progesterone receptor levels. These data suggest a differential interaction by LY117018 in the rat uterus so that only selected estrogen stimulated effects i.e.: uterine wet weight, are antagonized by this particular "antiestrogenic" dose of the drug.

Animals↗
PubMed1983

Characterization and assay of progesterone-binding components in DMBA-induced rat mammary carcinoma tissue after progesterone administration.

Nuclear and cytoplasmic progesterone-binding components were characterized and measured in DMBA-induced rat mammary carcinoma tissue, before and after progesterone administration. Rats, bearing growing tumors, were ovariectomized and then primed for two days with estradiol. Biopsy specimens were taken prior to or following administration of progesterone. Nuclear binding was assayed in the 0.4 M KCl extract of the nuclear fraction using [3H]R5020 as ligand. The receptor character of the binding was demonstrated by: (1) high affinity (Kd approximately 2 nM); (2) specificity: competition by R5020 and progesterone, minimal competition by 17 alpha-hydroxyprogesterone, corticosterone, testosterone and estradiol; (3) sedimentation constant at about 3S in a sucrose density gradient. Similar characteristics displayed the cytoplasmic receptor before and after progesterone administration. Progesterone receptor distribution in the nuclear extract and cytosol were determined in 36 tumors. The levels of total receptors (cytoplasmic plus nuclear) before and after progesterone administration varied widely, however the average values found after progesterone administration were significantly lower, 1.59 +/- 0.20 pmol/mg DNA compared to 2.58 +/- 0.32 pmol/mg DNA. Before progesterone administration only cytoplasmic receptors were found. One hour after progesterone administration a variable amount of the receptor (0-40%) was found in the nucleus of the tumorous tissue. In uteri of the same rats a uniform distribution of receptors (about 40% in the nucleus) was found after progesterone administration. A defect in the translocation process might be considered in the tumors with low receptors level, which suggests that DMBA-tumors may not respond uniformly to progesterone administration.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Characterization and stabilization of progesterone receptors in human benign prostatic hypertrophy.

Experimental conditions for the optimum detection and measurement of the cytosolic progestogen receptor in human prostatic hyperplasia and neoplasia are described. In presence of 20 mM molybdate ion and a reaction time of 0.5-2 h at 0-2 degrees C, we are able to detect the appearance of a [6.7-3H]-17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione ([3H]-R5020) and [3H]-progesterone binding moiety in human prostatic cytosol. The [3H]-R5020 binding protein sediments at approximately 8-11S in a glycerol density gradient centrifuged in a Sorvall TV865 rotor (vertical rotor). Maximal binding of [3H]-R5020 occurs at 30 min at 25 degrees C and 1 h at 0 degree C. Considerable overall improvement in receptor detection and measurement was made when gradient centrifugation was carried out in a vertical rotor instead of swing bucket rotor. The specifically bound [3H]-R5020 is displaced by progesterone, triamcinolone acetonide and R5020, but not by cortisol, dihydrotestosterone, 17 beta-estradiol, or diethylstilbestrol. High affinity was demonstrated by Scatchard analysis on binding of [3H]-5020 to receptors from cytosol of benign prostatic hypertrophy (BPH) giving a KD of 2.4 X 10(-10)M and a binding site concentration of 50 fmol/mg protein. Molybdate ion maintains the hormone receptor complex in 8-11S form which is totally converted to the 4-5S form in the presence of 0.6 M K Cl. The optimum concentration of fluoride ion for enhancing the specific binding of [3H]-R5020 was determined to be between 20 and 50 mM. Cytosol from human BPH in the presence of 25 mM sodium fluoride contains [3H]-R5020 receptors which sedimented mostly in the 4-5S region of glycerol density gradient. Sodium-molybdate and sodium fluoride stabilize and stimulate the specific [3H]-R5020 receptor complex at 25 and 0 degree C. The loss of specific receptor hormone binding capacity can be reversed by fluoride and, to a lesser extent, by molybdate.

Centrifugation, Density Gradient↗
PubMed1983

Interaction of medroxyprogesterone acetate with cytosol androgen receptors in the rat hypothalamus and pituitary.

The binding of medroxyprogesterone acetate (MPA) with cytosol androgen receptors from rat pituitary and hypothalamus was studied. The pituitary and hypothalamic cytosol androgen receptors from adult castrated female rats were in vitro labeled using 3H natural (testosterone (T) and 5 alpha-dihydrotestosterone (DHT] and [3H]synthetic (methyltrienolone) androgens as radioligands. The [3H]androgen-receptor complexes sedimented with a coefficient of 8S in linear sucrose gradients. When incubated with an excess of radioinert MPA, specific binding was abolished indicating interaction of MPA with androgen receptors. Furthermore specific [3H]MPA-androgen cytosol receptor complexes could be identified in these neuroendocrine tissues when a post-gradient receptor labeling technique was used in the absence or presence of radioinert MPA, DHT, and triamcinolone acetonide. A study of binding kinetics disclosed that the equilibrium dissociation constant and saturation binding capacity for the MPA binder, were similar to those exhibited by DHT binding to androgen receptors in both studied tissues under identical experimental conditions. The overall results were interpreted as demonstrating that MPA interacts with cytosol steroid receptors other than those of progesterone in the rat hypothalamus and anterior pituitary. The data are consistent with MPA binding to androgen receptors.

Animals↗
PubMed1983

Cytoplasmic progesterone receptors in the hypothalamus-preoptic area of the mouse: effect of estrogen priming.

A synthetic progestin, R5020, was used to identify cytoplasmic progestin receptors in the hypothalamuspreoptic area (HPOA) of ovariectomized mice. These high-affinity receptors exhibited an apparent dissociation constant of approx. 1 nM. The receptors were specific for progestins. [3H]R5020 binding was inhibited by more than 50% with a 50-fold excess of either radioinert R5020 or progesterone. 5 alpha-Dihydroprogesterone inhibited binding to a lesser extent. 3 alpha-Hydroxy-5 alpha-pregnane-20-one and cortisol did not compete for [3H]R5020 binding. Administration of estradiol benzoate (10 micrograms), 48 h prior to death, resulted in a 54% increase in the HPOA progestin receptor concentration when compared to oil-injected controls. These data demonstrate that there are specific and saturable cytoplasmic progestin receptors in the mouse HPOA and that the concentration of these receptors is increased after estrogen treatment.

Animals↗
PubMed1984

Monoclonal antibody to the hen oviduct progesterone receptor produced following in vitro immunization.

The progesterone receptor of the hen oviduct is composed of two non-identical hormone-binding polypeptide subunits, A (Mr = 79,000) and B (Mr = 108,000). We used a highly purified preparation of B to immunize mouse spleen cells in vitro. After 5 days in culture, the cells were fused with SP2/0-Ag 14 myeloma cells. The resultant hybridomas were screened using an enzyme linked immunosorbent solid phase assay, and those hybridomas producing antibodies binding to the immunogen were cloned by limiting dilution. One such clone, 9B3-12, secreted an antibody of immunoglobulin class IgM, which binds to B. This was indicated by the ability of the antibody to increase the rate of sedimentation coefficient of the B subunit. Further, when the proteins in the B preparation were separated by electrophoresis and blotted onto nitrocellulose filters the antibody bound to a protein of 108,000 daltons. The antibody produced by 9B3-12 also reacted with subunit A and with the human progesterone receptor but failed to bind to the chick liver glucocorticoid receptor or to progesterone in the absence of its receptor.

Animals↗
PubMed1984

Steroidal and nonsteroidal antiestrogens in breast cancer cells in culture.

The mode of action of two types of antiestrogens, tamoxifen and progestins, has been studied in the estrogen responsive cell lines, MCF7 and T47D, established from metastatic human breast cancer. (1) Non steroidal antiestrogens: We present evidence indicating that tamoxifen inhibits the growth of breast cancer cells via an interaction with the estrogen receptor (RE), which leads to a partial activation of the receptor and a dissociated effects on gene expression. At concentrations of less than 4 microM, effects of non steroidal antiestrogens are only observed when RE sites are available. At concentrations greater than 4 microM, an additional (cytotoxic?) effect of tamoxifen is observed which is not mediated by the RE. (2) Progestins: Direct antiestrogenic effect of progestins (R5020, progesterone) on breast cancer cells have been demonstrated. Three series of responses to R5020 are obtained: (a) A decreased cell proliferation (antiestrogenic and progestin specific effect). (b) A decreased production of total proteins in the culture medium (antiestrogenic effect). (c) The increased production of a 48,000 dalton protein which is released into the medium after treatment with several progestins (progesterone, medroxyprogesterone acetate, R5020) but not other steroids (specific progestin effect). These responses appear to be mediated by the progesterone receptor and are not observed in RP negative cell line (BT20). Even though these two types of antiestrogens inhibit cell proliferation via different receptors, a common final mechanism (decreased production of estrogen induced growth factors or increased production of antiestrogen induced inhibitory factor) is not excluded.

Breast Neoplasms↗
PubMed1984

Genetic analysis of dexamethasone resistance in L cells by somatic cell hybridization.

Stable dexamethasone resistant and receptor-containing (R+) variants of L cells have been characterized by somatic cell hybridization. Neither of the variants had a clearly dominant phenotype in hybrids with dexamethasone-sensitive fibroblast lines, i.e. the resistance of the variants was not due to transdominant factors. Somatic cell hybrids formed between one of the R+-resistant clones and an independent resistant fibroblast cell line showed complementation--the hybrid clones were as sensitive to the steroid as the sensitive parental lines. Complementation, however, disappeared after continued culture of the clones. The return of the dexamethasone-sensitive phenotype was not always linked with similar changes in the responsiveness to another steroid, e.g. progesterone. Our clones can be considered to be resistant variants, designated death-less (d-), where the cells are defective in a non-receptor component involved in the hormone response. The fact that complementation can occur indicates the existence of at least two such steps in the pathway.

Animals↗