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Results for “Progesterone Congeners”

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At least 37 records · Page 2Linked to original sources
PubMed1998

Cell surface binding sites for progesterone on human spermatozoa.

This study demonstrates the presence of [3H]-progesterone binding protein on the cell surface of human spermatozoa. The binding protein is masked and is exposed after treatment of spermatozoa with surfactants such as digitonin. Specific binding of [3H]-progesterone is observed after the washed spermatozoa or the crude cell membrane fractions are treated with 0.1% digitonin at 0-4 degrees C for 30 min R5020, 17alpha-hydroxyprogesterone and testosterone only partially compete with [3H]-progesterone for binding whereas the synthetic steroids STS557, RU486, ZK98.299 and ZK98.734 do not competitively inhibit the binding of [3H]-progesterone to spermatozoa. Progesterone binding sites are located in the acrosomal region of spermatozoa, as indicated by the use of fluorescein isothiocyanate-labelled progesterone-bovine serum albumin. The binding protein cross-reacts with the monoclonal antibodies to uterine progesterone receptor and has a molecular weight of approximately 85 kDa. This is the first study which demonstrates the presence of masked progesterone binding sites on the cell surface of human spermatozoa that are exposed after treatment with surfactants. These binding sites seem to have structural homology with the intracellular progesterone receptor but differ in terms of ligand specificity and location. The study further demonstrates that follicular fluid facilitates progesterone binding to spermatozoa.

17-alpha-Hydroxyprogesterone↗
PubMed1982

Synthesis of a new disulfide affinity adsorbent for purification of human uterine progesterone receptor.

For purification of the human uterine progesterone receptor, an affinity adsorbent was synthesized in which the specific ligand (16 alpha-ethyl-3-oxo-19nor-androst-4-ene 17 beta-carboxylic acid) was bound to derivatized celulose using a disulfide-group-containing spacer. The purified receptor protein, isolated by reductive cleavage of the disulfide bond, bound the synthetic gestagen R5020 with high affinity (Kd 12.2 nmol/l). The affinity gel was highly efficient. A 24000-fold purification of progesterone receptor with a recovery of 40% could be achieved in a single step within 6 h. By means of dodecyl sulphate/polyacrylamide gel electrophoresis two main polypeptides with molecular weights of about 43000 and 108000 could be demonstrated.

Adsorption↗
PubMed1984

Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy.

Earlier work showed that in a group of women suffering from partial epilepsy, there is a decrease in seizure frequency during the luteal phase of the menstrual cycle. Moreover, iv progesterone infusions decrease the discharge frequency from penicillin epileptic foci in cats, when given in doses that reach plasma concentrations as observed during pregnancy. In the present study, iv progesterone infusions, reaching plasma concentrations as during the luteal phase, were given to 7 women with partial epilepsy. The inclusion criterion was that they should have more than one epileptic discharge per 5 min on an ordinary EEG . A 6 h EEG-registration was made. Blank and progesterone solutions were infused for 2 h respectively and the progesterone infusion was followed by a 2 h EEG recording period. 4 of the 7 patients showed a significant decrease in spike frequency during the infusion. In the patients not showing this effect, the plasma progesterone binding capacity was high. The 2 patients with the most marked progesterone effect had low progesterone binding capacity and no antiepileptic treatment. Somnolence during the test might also have influenced the results in 2 of the patients.

Action Potentials↗
PubMed2006

Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs).

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil.

Animals↗
PubMed1984

The nuclear uptake and retention of a synthetic progestin in the cardiovascular system of the baboon.

It has long been known that there is a sexual dimorphism in the incidence of coronary heart disease. This observation, together with more recent reports of increased cardiovascular disease associated with the use of oral contraceptives, led to a search for steroid receptors in the cardiovascular system. In this study we examined the nuclear uptake and retention of a synthetic progestin in the cardiovascular system of the baboons. Long term oophorectomized baboons were primed with estradiol benzoate for 3 days before the experiment (50 micrograms/kg, im) and adrenalectomized 2 days before the experiment. On the day of the experiment, the animals were injected under anesthesia with 2.5 micrograms/kg BW [3H]ORG 2058 (16 alpha-ethyl-21-hydroxy-19-nor-[6,7-3H]pregn-4-ene-3,20-dione) or with [3H] ORG 2058 plus a 1000-fold excess of unlabeled progesterone (control). One hour after the injection, the animals were rapidly exsanguinated, and parts of the cardiovascular system were removed and processed for autoradiography. Localization of the synthetic progestin was found in nuclei of between 25-75% of all smooth muscle cells of the media of all arteries examined and to a lesser extent in the nuclei of the fibroblasts and others cells of the adventitia. Localization of the synthetic progestin in the heart was limited to approximately 1% of the myocardial cells and less than 5% of interstitial cell nuclei. The pattern of localization found differs from that for estrogen and androgen and suggests the possible presence of estrogen-independent progesterone receptors in smooth muscle cells of the media of the aorta and coronary arteries.

Adrenalectomy↗
PubMed1999

The antigonadotropic activity of a 19-nor-progesterone derivative is exerted both at the hypothalamic and pituitary levels in women.

We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function [McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 microg, i.v.), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-acting GnRH agonist administration. In women with FHA, pulsatile GnRH (20 microg s.c., every 90 min) was given for two cycles with or without NOMA (5 mg for 21 days). In all NC women, ovulation was suppressed by NOMA. Mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. In MCA, neither NOMA nor GnRH agonist modified multiple ovarian cysts on ultrasound or plasma E2, levels which remained elevated, ruling out a direct ovarian effect. In FHA, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle. Addition of NOMA prevented the increase of plasma E2, decreased the amplitude of LH pulses, and prevented ovulation. In view of this unexpected action of NOMA at the pituitary level, seven samples of normal human female pituitaries were tested for the presence of progesterone receptor (PR) using a double labeling immunocytochemical technique. The presence of PR was detected in the seven human pituitary tissues. In addition, PR was found to be expressed only in gonadotroph cells. In conclusion, NOMA, a 19-nor-P derivative, has a potent antigonadotropic activity exerted at the hypothalamic level, inhibiting ovulation in NC women. In women with FHA, NOMA decreased the gonadotropin stimulation induced by pulsatile GnRH administration. According to the presence of PR in gonadotroph cells of normal human pituitaries, 19-nor-progesterone derivatives may also act on the gonadotropin secretion at the pituitary level.

Adolescent↗
PubMed1986

Properties of progestin-binding protein in benign hypertrophic human prostate.

RU 27987 is a new ligand for progesterone receptor and binds in high affinity to nuclei of target tissues of progesterone. Using this compound, progestin-binding components in the benign hypertrophic human prostate were studied, and compared with those examined with R 5020, a conventional ligand, in the study of progesterone receptor. In cytosols, the binding affinity of RU 27987 was higher than that of R 5020, and the number of maximum binding sites for RU 27987 seemed to be large but correlated well with those of R 5020. The binder for RU 27987 sedimented at 8.6 S, and the binding was specific to progestational steroids, indicating that binding properties of this binder in the cytosols are identical to those for R 5020. Although there was no binding with R 5020 in the nuclear extract, a small amount of specific binding with RU 27987 was detected. However, the cytosol bound with RU 27987 was not retained in DNA Sepharose and no specific binder for RU 27987 in the nuclear extract was observed in a sucrose density gradient centrifugation. From these observations, it was assumed that the nuclear binding observed was attributable to contamination of the cytosolic binder. The results obtained in the present study suggest that the progestin-binding component in the benign prostatic hypertrophy is not the progesterone receptor but a high affinity binder for progestins whose physiological role is not clear at present.

Alpha-Globulins↗
PubMed2002

[Utrogestan--an alternative for synthetic gestagen treatment in spontaneous abortion].

A clinical trial is conducted with 32 pregnant patients with a history of sterility and infertility, uterine malformations as well as progesterone deficiency. The mean week of gestation is 9-10. All patients were treated with Utrogestan in the usual doses 2 x 100 mg for vaginal application. No side effects were observed which is encouraging to its routine use.

Abortion, Spontaneous↗
PubMed1988

[Progestogen therapy in the treatment of endometrial cancer--clinical results and mechanism of steroid action].

The use of medroxyprogesterone acetate (MPA) in therapy of patients with endometrial cancer has been recently examined by the Japan Gynecological Cancer Treatment Group. The response rate of oral MPA was 23.6% (13/55 evaluables) and the average period up to the onset of response was 15.2 weeks (4-28 wks). The response rate was higher in well-differentiated tumors than in poorly differentiated ones. Although it is well known that steroid hormone action is mediated by steroid hormone receptor, the presence of progesterone receptor in cancer tissue seems to be not absolutely necessary for the responsibility to MPA, a potent progestational compound. The reason was studied, in vitro, in our laboratory by using the technique of human tumor clonogenic assay. In this system, MPA showed a marked suppressive effect on the colony formation of endometrial cancer cells. Similar effects were also observed with progesterone, 17 alpha-hydroxyprogesterone caproate and megestrol acetate. Norethindrone and norgestrel, which are both potent progestational compounds, showed almost no anticancer activity on Ishikawa cell in this in vitro system. It became clear that progestational activity was not always associated with anticancer activity, and norethindrone had no influence on the inhibitory effect of MPA, although norethindrone has a strong affinity for progesterone receptor. Similarly, RU 486, which is known as a potent antiprogestogen agent and has a high affinity to progesterone receptor, did not influence the effect of MPA. These results clearly indicated that the anticancer activity of MPA was not mediated by high affinity low capacity progesterone receptor, and a pharmacological effect must be considered for understanding the effect of MPA on endometrial cancer.

Estrenes↗
PubMedDate not supplied

[Luteal insufficiency and elevation of sex-binding proteins by demegestone].

Demegestone, a norprogesterone derivative, was administered during the luteal phase in 6 normally ovulatory women and in 10 patients with luteal insufficiency. Demegestone decreased the LH surge and the plasma concentrations of estradiol and progesterone in the normally ovulatory women and did not modify the binding capacity of sex steroid binding protein (SBP). In the patients with luteal insufficiency, demegestone increased significantly SBP (0.94 +/- 0.24 vs 1.32 +/- 0.56 micrograms/dl, p less than 0.05) and decreased the free testosterone index (T/SBP) (38.8 +/- 33.3 vs 25.4 +/- 18.5, p less than 0.05). Transcortin, was unchanged during demegestone treatment in both groups of women. The results showed that demegestone did not exercise androgenic activity on SBP conversely to the nortestosterone derivatives which decrease SBP and confirmed that progesterone and norprogesterone derivatives influence positively the regulation of SBP.

Adult↗