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PubMed1987

Comparison of serum progesterone levels in dogs after administration of progesterone by vaginal tablet and vaginal suppositories.

Serum progesterone levels from a vaginal tablet formulation and six different vaginal suppository formulations, each containing 25 mg of progesterone, were evaluated in mongrel dogs. Bioavailabilities relative to an intravenous dose of progesterone were calculated. The vaginal tablet was found to have a significantly higher bioavailability compared with the vaginal suppositories.

Administration, Intravaginal↗
PubMed1984

Progesterone in the ventromedial hypothalamus of ovariectomized, estrogen-primed rats inhibits subsequent facilitation of estrous behavior by systemic progesterone.

The putative neural target sites of progesterone's (P) inhibitory influence on estrous behavior were re-examined utilizing intracranial hormone implants. Subjects were estrogen-primed ovariectomized, Long-Evans rats, and all were outfitted with permanent indwelling guide cannulae aimed for the ventromedial hypothalamus (VMH), preoptic area (POA), or midbrain. In a series of 4 weekly testing paradigms, the ability of blank or P-filled implants to both facilitate estrous responsiveness and to interfere with an animal's ability to exhibit estrous behavior following a systemic injection of P 24 hours later was assessed. P-filled implants placed bilaterally into the VMH inhibited the subsequent facilitation of estrous behavior by systemic P administration. Neither P-filled implants in other brain regions nor blank implants lowered into the VMH had this same effect. Seven of the females that exhibited progesterone-induced behavioral refractoriness 24 h after P stimulation of the VMH exhibited facilitation of estrous responsiveness in behavioral tests given 4.5 h after cannulae placement suggesting that progesterone may exert its facilitative and inhibitory actions on estrous responsiveness at the same neuroanatomical locus.

Animals↗
PubMed1977

Progesterone in the uterus. VII. Uptake of cortisol and incorporation of progesterone under simultaneous application of cortisol into rat uterus.

After injection of radioactively labelled cortisol, the distribution of the radioactivity in the subcellular fractions of the rat uterus (nuclei, mitochondria, microsomes and 105 000 X g supernatant) was studied. In all fractions, radioactivity was observed and maxima were found 10, 20 and 50 min. after injection of the labelled hormone. Radioactivity was measured in all subcellular fractions even 180 min. after application of labelled cortisol. Additionally, radiolabelled progesterone and unlabelled cortisol in the ratio 1:1 or 1:2 (moles:moles) were injected into the animals. Studying the uptake of labelled progesterone in the subcellular fractions of the uterine tissue, revealed that no competition of unlabelled cortisol could be observed 10, 20 and 50 min. after application of the hormone mixture, compared with the control experiments. The results of this study give evidence that the progesterone uptake into rat uterus is specific and cannot be influenced by unlabelled cortisol.

Animals↗
PubMed2002

6alpha-Methyl-16alpha,17alpha-cyclohexane progesterone and progesterone inhibit growth of doxorubicin-sensitive MCF-7 and HeLa tumor cells.

Temporal and concentration dependencies of the effects of gestagens (6alpha-methylpentarane and progesterone) and cytostatic doxorubicin on proliferation of MCF-7 and HeLa tumor cells was studied using(3)H-thymidine test. Gestagens produced the maximum inhibitory effect of on cell proliferation in a concentration of 10(-5)M; the effect developed on day 6 of incubation. 6 alpha-Methylpentarane in a concentration of 10(-8)inhibited proliferation of HeLa cells more effectively than progesterone (p<0.05). In experiments with combined treatment of doxorubicin-sensitive MCF-7 and HeLa cells, progesterone in a concentration of 10(-7)M attenuated the cytostatic effect of doxorubicin (p<0.05), while 6alpha-methylpentarane in the studied concentrations did not modulate it.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.

BACKGROUND: This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells. METHODS: PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis. RESULTS: Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells. CONCLUSIONS: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.

Adrenomedullin↗
PubMed1997

Autoimmune progesterone dermatitis: onset in a women without previous exogenous progesterone exposure.

Autoimmune progesterone dermatitis is a rare clinical entity that may be seen by the family practitioner, gynecologist, or dermatologist. Recognition of the entity is paramount in the therapy of this easily treated condition. We report a case of a 36-year-old woman with a recurrent facial dermatitis of many months' duration. We found the cutaneous eruption to be temporally related to her menstrual cycle. The patient denied any changes in her diet, cosmetics, medications, or soaps that could account for the dermatitis. Despite no previous exposure to exogenous progesterone, the diagnosis of autoimmune progesterone dermatitis was made. The patient was cured by oophorectomy.

Adult↗
PubMed1989

The effects of duration and concentration of plasma progesterone on the fertility of post-partum cows treated with pregnant mare serum gonadotrophin and intravaginal progesterone.

The effects of duration of insertion of progesterone releasing devices (PRIDs) on the concentrations of plasma progesterone (plasma P4) and the relationship of these with fertility were examined respectively in ovariectomised and intact Bos taurus cattle. In experiment 1, ovariectomised cows (n = 14) were treated with PRIDs to produce high and low plasma P4 for 7 or 14 days giving 4 treatment groups designated H7, H14, L7 or L14. Mean plasma P4 in the H14 and L14 groups were 6.6 and 6.0 ng/ml respectively, during the first week and 5.4 and 3.8 ng/ml respectively, during the second. Mean plasma P4 of 6.3 and 4.2 ng/ml were observed in H7 and L7. In experiment 2, suckled cows (n = 171) received the same PRID treatments as cows in experiment 1, plus either 375 or 750 iu pregnant mare serum gonadotrophin, and subsequent calving rates were recorded. These were significantly lower after L7 than the other treatments (12% v 38%, P less than 0.025). These results showed that fertility after oestrus was closely related to plasma P4 observed before oestrus and indicated that treatment with progesterone for as little as 1 week can produce normal fertility providing plasma P4 attain a critical threshold during treatment.

Animals↗
PubMed2001

Suppression of ovarian progesterone production in dairy cows using an implant of GnRH-agonist (deslorelin) for the purpose of evaluating progesterone metabolism [corrected].

OBJECTIVE: To evaluate the potential of an implant of a GnRH-agonist (deslorelin) to create a progesterone free animal suitable for studying progesterone (P4) metabolism in intact cows by measuring blood P4 and faecal P4 metabolites. METHODS: Experiment 1: Eighteen non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to one of three groups to study plasma P4 concentrations preceding an intravaginal insert. These groups comprised: i) a deslorelin group (GnRH-agonist implanted); ii) a PGF group receiving two injections of prostaglandin (PGF2alpha) 12 days apart; and, iii) an ovariectomised (OVX) group. An intravaginal device (CIDR) was inserted into the vagina of each animal and left in place for 11 days. Plasma P4 concentrations were measured during the study period. Experiment 2: Twelve non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to two groups: i) a deslorelin group (GnRH-agonist implanted); and ii) an ovariectomised group. Plasma P4 and faecal P4 metabolites (20-oxo-pregnanes, 20alpha-OH and 20beta-OH) were monitored for a period of 5 weeks. RESULTS: Experiment 1: Average plasma P4 concentration did not differ between the three groups (1.28, 1.43 and 1.55 ng/mL for deslorelin, OVX and PGF cows, respectively, P = 0.8) during the period of supplementation. Experiment 2: There was no difference in plasma P4 (mean plasma P4 < 0.02 ng/mL, P = 0.9) and faecal P4 metabolites between deslorelin and OVX cows 2 weeks after the implantation (P = 0.7). CONCLUSIONS: These data showed that a GnRH-agonist (deslorelin) implant may be used as an alternative to ovariectomy to create a progesterone free animal suitable for studying the metabolism of administered P4.

Administration, Intravaginal↗
PubMed2002

Progesterone receptors - animal models and cell signaling in breast cancer: Role of steroid receptor coactivators and corepressors of progesterone receptors in breast cancer.

Progesterone, an ovarian steroid hormone, plays a key role in the development and function of the mammary gland, as it also does in the uterus and the ovary. The action of progesterone is mediated through its intracellular cognate receptor, the progesterone receptor (PR), which functions as a transcription factor that regulates gene expression. As with other nuclear receptors, coregulators (coactivators and corepressors) recruited by the liganded or unliganded PR, either to enhance or to suppress transcription activity, modulate the function of the PR. Mutation or aberrant expression of the coregulators might thus affect the normal function of the PR and hence disrupt the normal development of the mammary gland, which may lead to breast cancer.

Animals↗
PubMed1978

Effect of a progesterone-releasing intravaginal device on the milk progesterone levels, vaginal flora, milk yield and fertility of cyclic and non-cyclic dairy cows.

A progesterone-releasing intravaginal device (PRID) was inserted for 14 days into 10 lactating dairy cows at least 50 days after calving. Synchronization of oestrus was good and 5 of the cows conceived to a double insemination 48 and 72 h after PRID removal. In 9 cows vaginal infection was present when the PRID was removed but resolved spontaneously. The level of progesterone in the milk and the milk yield were similar to those in the 10 control animals. PRID treatment of 9 cows whose ovaries had remained inactive for at least 50 days after calving was followed by ovulation, as judged by the milk progesterone profile, in 8 animals after removal of the device.

Anestrus↗
PubMed1982

Plasma concentrations of prolactin, progesterone, relaxin and oestradiol-17 beta in sows treated with progesterone, bromocriptine or indomethacin during late pregnancy.

Pregnant gilts (3/group) were given no treatment, 10 mg bromocriptine twice daily by mouth, from Day 111 of pregnancy to 1 day post partum, 25 mg progesterone s.c. at 6-h intervals from Days 111 to 116 inclusive or 400 mg indomethacin by mouth at 6-h intervals from Day 111 to 116 inclusive. Before spontaneous delivery maternal plasma prolactin and relaxin concentrations started to rise almost simultaneously between 58 and 47 h before the first piglet and both hormones reached peak values when the plasma progesterone concentration had started to decline rapidly (approximately 21-23 h). Suppression of prolactin levels by bromocriptine prevented the onset of lactation completely but had no obvious influence on changes of the other hormone concentrations and the course of parturition. Progesterone treatment delayed the onset of expulsion of the piglets but did not delay the simultaneous increase in prolactin and relaxin concentrations. These changes in hormone levels were prevented by indomethacin treatment but occurred essentially unchanged when the treatment was ended. The results support the concept that parturition in the pig is preceded by a biphasic increase of plasma prostaglandin levels.

Animals↗
PubMed2000

Treatment of noncyclic lactating dairy cows with progesterone and estradiol or with progesterone, GnRH, prostaglandin F2 alpha, and estradiol.

The efficacy of two programs for treating noncyclic cows was compared. In trial 1, 478 cows in five herds were randomly divided into two groups. Cows in one group (C group) were treated with an intravaginal progesterone device for 8 d followed in 48 h by 1 mg of estradiol benzoate to cows that had not been detected in estrus since device removal. Those in the other group (CGP group) were treated with progesterone and estradiol as for the C group plus 10 micrograms of a GnRH agonist (buserelin) at device insertion and 25 mg of PGF2 alpha 7 d after device insertion. In trial 2 with 729 cows in nine herds, the treatments were similar to those in trial 1 except that the duration of progesterone treatment was 7 d. No significant difference was found between trials and results from both trials were combined. Compared with C group cows, CGP group cows had a greater estrous response rate (93.2 vs. 89.1%), a greater conception rate to first artificial insemination (AI, 47.1 vs. 29.4%), marginally lower conception rate to second AI (52.9 vs. 59.7%), lower nonpregnancy rate (8.3 vs. 11.1%), and shorter intervals from the start of breeding to conception by AI (9.8 vs. 15.3 d) or by AI or natural mating (21.6 vs. 26.3 d). The treatment protocol used for the CGP group achieved better reproductive performance than that used for the C group.

Animals↗
PubMed1985

Chemiluminescence immunoassay of plasma progesterone, with progesterone-acridinium ester used as the labeled antigen.

This simple solid-phase chemiluminescence immunoassay for measurement of progesterone in extracts of venous plasma has sensitivity and precision similar to that of conventional radioimmunoassay with use of a tritiated antigen. The labeled antigen, 11 alpha-progesteryl-2-succinoyltyramine-4-(10-methyl)-acridini um-9-carboxylate, and a monoclonal antibody to progesterone-11 alpha-succinyl-bovine serum albumin are incubated with a 100-microL aliquot of plasma extract (equivalent to 20 microL of plasma) and 50 microL of a suspension of an IgG fraction of a donkey antiserum to mouse immunoglobulins, covalently attached to cellulose particles. After the antibody-binding reaction (60 min at 4 degrees C), 1 mL of phosphate buffer is added to each tube, the tubes are centrifuged (5 min, 1500 X g), and the supernatant fluid is aspirated. The washing step is repeated and diluted hydrochloric acid (50 mmol/L, 50 microL) is added to the pellet. Luminescence is initiated by oxidation with dilute sodium hydroxide/hydrogen peroxide. The signal is integrated over 10 s. The light yield is inversely proportional to the progesterone concentration in the standard or sample.

Acridines↗
PubMed1981

Progesterone and insulin resistance. III. Time-course study of progesterone action on differentially labelled 14C-glucose utilization by adipose tissue and isolated adipocytes of the female rat.

Progesterone action on glucose metabolism was evaluated on parametrial fat pads and on isolated adipocytes using glucose labelled on C1, C2 and C6, (1) The steroid decreased the pentose cycle, but had no effect on the krebs cycle as judged by the C5/C1 ratio. (2) The radiorespirometric method, in combination with appropriately labelled glucose, demonstrated a rapid in vitro effect of progesterone on oxidation of (1-14C)-glucose. This finding suggest that progesterone acts on the glucose metabolism of the adipose tissue by a non-classical mechanism of steroid hormone action.

Adipose Tissue↗
PubMed1997

Characterization of progesterone membrane binding sites from porcine liver probed with a novel azido-progesterone radioligand.

A new derivative of progesterone was synthesized for photoaffinity labelling of specific binding sites in porcine liver microsomes. Using progesterone-3-(O-carboxymethyl)-oximino-(3-125I-iodo-4-azidosa licylamidobutylamine) as a photoactivatable radioligand, selective covalent labelling of proteins was detected in porcine liver microsomes at apparent molecular weights of 90-100 kDa and 60-65 kDa by SDS-PAGE and subsequent radioautography. These proteins showed different ligand specifity for various steroids tested. On blue native polyacrylamide-gels three selectively labelled proteins were found corresponding to apparent molecular weights of approximately 310 kDa, approximately 215 kDa and approximately 75 kDa, respectively. Using two-dimensional electrophoresis for the analysis of these protein complexes, the 215 kDa-band could be correlated to the 90-100 kDa-band, while the 75 kDa-band may correspond to the 60-65 kDa-band at one-dimensional SDS-PAGE, respectively. One or more of these proteins may be involved in the rapid progesterone-induced increase of intracellular Ca2+ described previously in cultured hepatic cells.

Affinity Labels↗
PubMed1987

The effect of progesterone on the localization of progesterone receptors in the nuclei of chick oviduct cells.

The location of occupied and unoccupied progesterone receptors (PR) in chick oviduct cells was studied by immuno-electron microscopy with the use of a highly specific polyclonal anti-PR antibody and pre-embedding modifications of the peroxidase-anti-peroxidase- (PAP-) or immunogold-silver methods. Both methods revealed a nuclear localization of the PRs. The location of the PR in the nucleus was studied in detail by means of the immunogold-silver method. The most intense labelling for unoccupied PRs was in the condensed chromatin. After occupation of PRs with progesterone (P), decondensation or dispersion of chromatin was observed. At the same time, the labelling in the border area of condensed and dispersed chromatin, and in the dispersed chromatin, increased. The changes were statistically significant. The results can be explained by conformational changes of the PR-containing chromatin rather than by translocation of PRs from one site to another.

Animals↗
PubMed1982

Progesterone-binding globulin and progesterone in guinea-pigs after ovariectomy, abortion and parturition.

The level of progesterone in the serum of pregnant guinea-pigs which continued their pregnancies after ovariectomy on Day 30 fell and then rose again. In contrast, progesterone-binding globulin (PBG) was apparently not affected. PBG did however fall in guinea-pigs which aborted and also after parturition. It is apparent therefore that high PBG levels were associated with continued pregnancy. The half life of PBG was found to be approximately 2 days.

Abortion, Spontaneous↗
PubMed1983

Analysis of progesterone receptor in the quail oviduct. Correlation between plasmatic estradiol and cytoplasmic progesterone receptor concentrations.

Specific binding sites for [3H]-progesterone are found in the cytosol fraction of the oviduct of castrated, immature and developing quails. The optimal conditions to accurately measure the total cytoplasmic concentration of this progesterone receptor are described. The dissociation constant (KD) at 0 degrees C is 3.6 +/- 0.6 x 10(-9) M (mean +/- SE) for [3H]-P and the concentration of binding sites is 13.4 +/- 2 pmol/mg DNA in immature animals. This binding capacity is not altered even 2 weeks after ovariectomy. During sexual development, although the dissociation constant remains unchanged, the number of binding sites increases to 74.5 +/- 1.6 pmol/mg DNA just before the beginning of the laying cycle. The concentration of cytoplasmic P receptor is under the inductive influence of estradiol. In castrated quails, estradiol 17 beta (E2) perfusion through the portal vein at a rate below or equal to 2 ng/min for 24 hr does not increase plasmatic E2 concentration and consequently does not change [3H]-P binding sites concentration in the oviduct. While E2 perfusion rate exceeds the metabolizing capacity of the liver (6.8 ng/min), both plasmatic E2 level and oviductal P receptor concentration are increased. When E2 is perfused through the jugular vein, plasmatic E2 level increases with the dose of E2 but P receptor concentration only increases when E2 perfusion rate reaches to 2.0 ng/min for 24 h.

Animals↗