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At least 145 records · Page 8Linked to original sources
PubMed1996

Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial.

Two different regimens of luteal support in gonadotrophin hormone-releasing hormone (GnRH) analogue/human menopausal gonadotrophin (GnRHa/HMG)-induced in-vitro fertilization cycle (IVF) were compared in a randomized clinical trial. After embryo transfer, either vaginal progesterone alone was administered (n = 89, P group), or a combination of vaginal progesterone and human chorionic gonadotrophin (n = 87, P/HCG group). The primary aim of this study was to assess the effect of the different regimens of luteal support on the pregnancy rate. The secondary aim was to compare oestradiol and progesterone concentrations in the luteal phase between the two groups, and assess their effect on the pregnancy rate. A clinical pregnancy rate of 15% was found in the P/HCG group in comparison with 26% in the P group (odds ratio 0.49; 99% confidence interval: 0.18-1.3). The luteal serum oestradiol and progesterone values in the P/HCG group were significantly higher when compared with the P group on the 6th, 9th and 12th day after oocyte retrieval (Wilcoxon P < 0.001). In accordance with the high oestradiol concentrations, more cases of ovarian hyperstimulation syndrome (OHSS) were found in the P/HCG group. Oestradiol values on the 9th day after oocyte retrieval, presumably the day of implantation, appeared to be higher in women who did not become clinically pregnant. We conclude that vaginal progesterone alone provides sufficient luteal support in GnRHa/HMG induced IVF cycles. The combination of vaginal progesterone and HCG as luteal support leads to significant high luteal oestradiol and progesterone concentrations. But a high concentration of oestradiol seems to have a deleterious effect on the implantation process, resulting in a low pregnancy rate.

Adult↗
PubMed1992

The effect of luteal support with human chorionic gonadotrophin or progesterone on the daily progesterone profile after different types of ovarian stimulation.

Attempts have been made to increase the low pregnancy rate in in-vitro fertilization (IVF) cycles by luteal phase support with progesterone or human chorionic gonadotrophin (HCG). Previously, this practice has been inconsistent and the results unclear. The detailed effect of support on the progesterone profile in the luteal phase was assessed by daily salivary progesterone measurements in non-conception IVF cycles. The comparison of HCG and progesterone support in two different stimulation protocols showed that the profile of luteal progesterone concentrations was similar in control cycles and those supported with a vaginal progesterone suppository, showing an early decrease by the fourth luteal day. In cycles supported with multiple doses of HCG, the progesterone profile was normal but slightly increased up to the 9th luteal day subsequently falling to basal levels by the fourteenth luteal day.

Chorionic Gonadotropin↗
PubMed1994

Autoimmune progesterone dermatitis: absence of contact sensitivity to glucocorticoids, oestrogen and 17-alpha-OH-progesterone.

Autoimmune progesterone dermatitis is a rare condition, characterized by recurrent premenstrual exacerbations of a dermatosis, in which sensitivity to progesterone can be demonstrated. The sensitizing mechanism is unknown. The aim of this study was to test the hypothesis that cross-sensitivity between steroid groups could induce allergy to endogenous progesterone in these patients. 5 patients with autoimmune progesterone dermatitis and 1 with oestrogen-sensitive dermatitis have been patch tested with a corticosteroid series, conjugated oestrogen 1% in petrolatum (pet.), and 17-alpha-OH-progesterone 2% pet. There were no immediate or delayed reactions at 2 and 4 days to any steroid group. We have therefore been unable to demonstrate steroid cross-sensitivity, or a use for 17-alpha-OH-progesterone in the investigation of oestrogen - and progesterone-sensitive dermatoses.

Adult↗
PubMed1988

Progesterone, some progesterone derivatives and urinary digoxin-like substances from pregnant women in radioimmuno- and 86Rb-uptake assays of digoxin.

Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.

Anesthetics↗
PubMed1993

Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers.

Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) humans. Consequently, we measured allopregnanolone and pregnanolone in 18 healthy females, ages 18-25, at the time of peak plasma progesterone following an oral dose of micronized progesterone (1,200 mg) in a double-blind, placebo-controlled study. The plasma levels of the parent steroid and metabolites were compared with changes in mood, cognition, and motor performance following progesterone administration. We observed good correlations between plasma progesterone and plasma allopregnanolone (r = 0.85), plasma pregnanolone (r = 0.81) and the combined metabolites (r = 0.92). Plasma allopregnanolone was significantly correlated with measures of fatigue, confusion and immediate recall, and these correlation coefficients were somewhat greater than those for plasma progesterone and these same behavioral measures. Significant changes in fatigue, delayed verbal recall and symbol copying were experienced by subjects who achieved high levels (> or = 95.55 nmol/l) of these anxiolytic metabolites, while those with lower metabolite levels reported no negative effects. These data suggest that allopregnanolone and pregnanolone may contribute to or mediate the observed behavioral effects of progesterone.

Administration, Oral↗
PubMed1982

Rate of ovarian progesterone secretion and peripheral plasma progesterone levels in unilaterally ovariectomized, pregnant rats.

Peripheral plasma progesterone concentrations were serially examined in 4 sham-operated and 5 intact rats (controls) and in 5 rats that were unilaterally ovariectomized on Day 8 of gestation. The characteristic rise in progesterone levels after Day 10 appeared to be delayed by 2 days in unilaterally ovariectomized rats but by Day 16 their levels were nearly normal. In a separate experiment a venous outflow technique was used to measure the rate of progesterone secretion from one ovary on Day 16 of gestation of 9 intact rats and the remaining ovary of 5 rats, unilaterally ovariectomized 8 days earlier. The rate of progesterone secretion was almost doubled in the unilaterally ovariectomized rats due to a substantial increase in arterio-venous different in plasma progesterone levels but no change in ovarian blood flow. This doubling was sufficient to explain the maintenance of peripheral plasma progesterone levels in unilaterally ovariectomized rats without postulating increased secretion from other organs or a decrease in metabolic clearance rate of progesterone.

Animals↗
PubMed1985

Comparison of the rate of decline in plasma progesterone concentrations at a natural and progesterone-synchronized oestrus and its effect on tonic LH secretion in the ewe.

The pattern of change in plasma progesterone and LH concentrations was monitored in Clun Forest ewes at a natural oestrus and compared to that observed after removal of progesterone implants. The rate of decline in plasma progesterone concentrations after implant withdrawal (1.8 +/- 0.2 ng/ml h-1) was significantly greater (P less than 0.001) than that observed at natural luteolysis (0.2 +/- 0.1 ng/ml h-1), and this resulted in an abnormal pattern of change in tonic LH secretion up to the time of the preovulatory LH surge. This more rapid rate of progesterone removal was also associated with a shortening of the intervals from the time that progesterone concentrations attained basal values to the onset of oestrus (P less than 0.05) and the onset of the preovulatory LH surge (P less than 0.01). However, there were no significant differences in the duration of the LH peak, preovulatory peak LH concentration, ovulation rate or the pattern of progesterone concentrations in the subsequent cycle. It is suggested that the abnormal patterns of change in progesterone and tonic LH concentrations may be one factor involved in the impairment of sperm transport and abnormal patterns of oestradiol secretion known to occur at a synchronized oestrus.

Animals↗
PubMed1989

Effect of treatment with progesterone on pregnancy rate and plasma concentrations of progesterone in Holstein cows.

Progesterone-releasing intravaginal devices inserted into the vaginas of dairy cows between d 5 to 12 (n = 28) or d 10 to 17 (n = 27) after insemination increased pregnancy rate to 60 over 30% in untreated control cows (n = 30). Plasma progesterone concentrations were increased during both progesterone treatments. Subtraction of the estimated contribution of exogenous progesterone indicated that endogenous, luteal progesterone was reduced during d 10 to 17 but not during d 5 to 12. Supplemental progesterone increased pregnancy rate but suppressed endogenous production of progesterone when administered during d 10 to 17 after insemination.

Administration, Intravaginal↗
PubMed1990

Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity.

We measured the concentration of progesterone and estradiol and calculated the progesterone:estradiol ratio in nonpregnant and pregnant human myometrium. Progesterone, estradiol and the progesterone:estradiol ratio were higher in pregnant than in nonpregnant myometrium. There was no difference in the concentration in the presence of labor. The progesterone:estradiol ratio showed a similar pattern. We also investigated the effect of the ovarian steroids on the activity of cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE). Progesterone in pharmacologic doses inhibited the activity of the high-affinity enzyme as much as 72% and the low-affinity form as much as 34%. High-affinity phosphodiesterase from nonpregnant myometrium was the least sensitive to inhibition, and the enzyme from pregnant myometrium obtained from laboring women was the most sensitive. Low-affinity phosphodiesterase from nonpregnant myometrium was less sensitive to inhibition than enzyme from pregnant women with or without labor. The degree of inhibition of the low-affinity enzyme in the two pregnant groups was not different. The type of inhibition was competitive in both the high- and low-affinity forms. Estradiol at similar concentrations did not have any effect on the activity of the enzyme. Progesterone in part may exert its effect on the human myometrium by its effect on cyclic adenosine monophosphate-PDE activity and the metabolism of cAMP.

Adenosine Monophosphate↗
PubMed1986

Characterization of estrogen and progesterone receptors and the dissociated regulation of growth and progesterone receptor stimulation by estrogen in MDA-MB-134 human breast cancer cells.

We have examined the properties of the estrogen receptor and progesterone receptor in MDA-MB-134 human breast cells and have evaluated the effects of estrogen on cell proliferation and progesterone receptor levels in these cells as indices of hormonal sensitivity. These cells contain high levels of estrogen receptor (approximately 1.5 pmol/mg DNA) and low levels of progesterone receptor (0.15 pmol/mg DNA). More than 80% of the estrogen receptor is found in the nuclear fraction in the absence of estrogen, and the Kd of the receptor for estradiol is approximately 1.5 X 10(-10) M. Upon exposure to estradiol, the receptors become occupied, but there is no processing or apparent decrease in either nuclear or total cellular estrogen receptor content, as can be seen in MCF-7 human breast cancer cells. The nuclear estrogen receptor sediments as a 4.6 S species on high salt sucrose gradients, and it can be detected on sodium dodecyl sulfate-polyacrylamide gel immunoblot analysis as a species of molecular weight 65,000, identical to that of the MCF-7 estrogen receptor, using the monoclonal antibodies D75P3 gamma and H222Sp gamma prepared against the MCF-7 estrogen receptor. The estrogen receptor shows binding selectivity for estrogens and antiestrogens, and its affinity for ligands follows the order diethylstilbestrol (190%) greater than estradiol (100%) greater than estriol (13%) greater than tamoxifen (3%), as expected for estrogen receptor. Hence the receptor appears normal in many of its physicochemical properties and in terms of its binding affinity and specificity for estrogens and antiestrogens. Control cells contain low levels of progesterone receptor that display high affinity (Kd = 6 X 10(-9) M) for the synthetic progestin R5020, but exposure to estradiol (10(-11)-10(-7)M) fails to increase cellular progesterone receptor levels. In contrast, estradiol markedly stimulates the rate of cell proliferation, while tamoxifen suppresses the growth of control and of estradiol treated cells. Hence, our data show that these cells, which contain substantial levels of estrogen receptor, respond to estrogen with enhanced cell proliferation but fail to have their progesterone receptor level modulated by estradiol. These cells represent an interesting and unusual situation in which estrogenic regulation of proliferation and the stimulation of progesterone receptor are dissociated. These cells should prove useful in further evaluation of estrogenic regulation of cell proliferation and specific protein synthesis in human breast cancer.

Antibodies, Monoclonal↗
PubMed1979

Plasma progesterone levels in progesterone treated cows.

A technique for the radioimmunoassay of progesterone in plasma is described. In one trial the oestrous cycles of four cycling cows and in another trial of one non-cycling cow and two cycling heifers were synchronized by the administration of progesterone. Each female received either 50 mg or 0,1 mg/kg of progesterone intramuscularly on alternate days in two courses of four and six injections respectively. Blood samples of the animals were collected either daily or two-daily before, over the entire period of treatment and for eight days after the last progesterone injection. The results of the progesterone assays are represented graphically for each individual cow or heifer. The plasma progesterone levels during treatment were maintained reasonably well at levels corresponding to those normally encountered during the lluteal phase of the cycle. The progesterone levels, however, did not drop as rapidly as desired after the last injection but might have been influenced by a residual corpus luteum from a previous ovulation.

Animals↗
PubMedDate not supplied

A comparative study of clomiphene and epimestrol on plasma progesterone, CBG, TBG and SHBG, and salivary progesterone levels.

The plasma levels of CBG, TBG, SHBG and progesterone, and salivary progesterone levels were measured in eight young ovulatory volunteers. After the control cycle four subjects received 50 mg/day of Clomiphene from days 5 to 9 of the first treatment cycle, and 10 mg/day of Epimestrol from days 5 to 15 of the second treatment cycle. The other four subjects received the treatments in reverse order. Between the two treatments there was one cycle without medication as a "wash-out" period. Plasma and saliva samples were obtained on days +6, +8 and +10 (day of LH peak was denoted by 0), always between 08.00 and 09.00 h. Statistical evaluation was done by means of an analysis of variance (ANOVA), and correlation coefficients were also calculated. Evaluation of data on effects of Clomiphene and Epimestrol on the plasma levels of CBG and salivary progesterone showed that Clomiphene induced a highly significant rise (p less than 0.001) in the CBG levels and decrease (p less than 0.001) in salivary progesterone levels, while no changes were seen following administration of Epimestrol. Both Clomiphene and Epimestrol treatments led towards higher plasma progesterone levels, those following Clomiphene administration being higher. Neither treatment induced significant changes in TBG or SHBG levels. It is concluded that Clomiphene induces significant elevations of CBG and decrease in salivary progesterone, which is thought to reflect the free progesterone fraction and may have significance in relation to a discrepancy between the ovulation and pregnancy rates following Clomiphene therapy.

Adult↗
PubMed1987

The effect of active immunization against progesterone on plasma concentrations of total and free progesterone, estradiol-17beta and LH in the cyclic ewe.

Nine mature cyclic ewes were actively immunized against progesterone which was rendered immunogenic by conjugation to bovine serum albumin (BSA). Seven control ewes were immunized with BSA. In ewes immunized against progesterone, the concentration of total plasma progesterone increased to 24.3 ng/ml vs 2.8 ng/ml in control animals (P<0.001). However, immunization did not affect the plasma levels of free, unbound progesterone. The correlation coefficient between total plasma progesterone concentrations on Days 4 to 11 of the estrous cycle and antibody titer was r=0.983. Estradiol-17beta concentrations in immunized ewes were higher than in controls on Days 6 to 15 of the estrous cycle (P approximately 0.05). Frequent sampling for LH over a 6-h period on Days 2, 5, 8, 11 and 14 of the cycle revealed no significant differences in the frequency and amplitude of LH pulses between immunized and control ewes. The immunized ewes had estrous cycles of normal length and maintained normal pregnancies. It is suggested that the immunized cyclic ewe is capable of maintaining adequate levels of free progesterone by greatly increasing progesterone synthesis, thus neutralizing the effect of the antibodies.

Journal Article↗
PubMed1984

Augmentation of progesterone receptor concentration by progesterone and estrogen treatments in the chick oviduct.

Cytosol receptors for progesterone in the chick oviduct were measured by charcoal-adsorption assay by using ORG 2058 as a ligand after long-term administration of progesterone and diethylstilbestrol (DES). Steroid administration was carried out by using daily injections or silastic capsules. DES treatment increased the progesterone receptor concentration (from 11500 to 21500 sites per cell, day 14). Progesterone also augmented the concentration of its own receptors (from 11500 to 29000 sites per cell, day 14). In the experiments with capsule administration the same trend was seen. This indicates that both diethylstilbestrol and progesterone are able to increase the concentration of progesterone specific cytosol receptors in the non-differentiated chick oviduct.

Animals↗
PubMed1983

Immunosuppressive effect of serum progesterone during pregnancy depends on the progesterone binding capacity of the lymphocytes.

Cytotoxic activity and progesterone binding capacity of the lymphocytes, together with serum progesterone concentrations, were determined in women with normal pregnancy or with a clinical diagnosis of threatened abortion or threatened premature labour. The lymphocytes of women with threatened abortion or threatened premature labour showed significantly higher cytotoxic activity (P less than 0.001) and significantly lower progesterone binding capacity (P less than 0.001) than did lymphocytes obtained from the healthy pregnant women. Significant inverse correlation was found between progesterone binding capacity and cytotoxic activity of the lymphocytes (P less than 0.001), but the progesterone concentration of the pregnancy serum appeared to have no influence on the other two parameters. The findings indicate that intact progesterone binding capacity of the lymphocytes is an essential factor for the manifestation of the blocking effect exerted by pregnancy serum on lymphocyte cytotoxicity in vitro.

Abortion, Threatened↗
PubMed2025

Progesterone receptor isoform modulation via enhancer activation regulates progesterone signaling in endometrial stromal cells.

OBJECTIVE: To investigate enhancer-mediated regulation of progesterone receptor (PGR) isoforms, PGR-A and PGR-B, in human endometrial stromal cells, and to determine how isoform modulation shapes the progesterone-responsive transcriptome and cistrome relevant to endometrial function. DESIGN: A clustered regularly interspaced short palindromic repeats-based functional genomic screen was used to identify distal enhancers in telomerase-immortalized human endometrial stromal cells. Subsequent clustered regularly interspaced short palindromic repeats targeting of identified enhancers and the PGR promoter was used to modulate PGR isoform balance and assess functional consequences. SUBJECTS: None. EXPOSURE: Engineered endometrial stromal cells were treated with medroxyprogesterone acetate or vehicle. MAIN OUTCOME MEASURES: PGR isoform expression was assessed by western blot, the progesterone-responsive transcriptome was characterized by bulk ribonucleic acid sequencing, and the PGR cistrome was characterized by Cut&Run. RESULTS: Two distal PGR enhancers were identified in endometrial stromal cells located approximately 60 and 220 kb upstream of the PGR transcription start site. Clustered regularly interspaced short palindromic repeats-based activation of these enhancers upregulated both PGR-A and PGR-B, whereas promoter activation primarily upregulated PGR-B. Bulk ribonucleic acid sequencing revealed that shifting the PGR isoform balance altered the progesterone-regulated transcriptome: PGR-A/B-equivalent cells exhibited proinflammatory gene signatures, whereas PGR-B-dominant cells demonstrated suppression of inflammatory signaling and altered cell cycle programs. The PGR Cut&Run profiling revealed distinct genomic binding patterns associated with each isoform profile. Integration of the PGR cistrome with chromatin interaction maps suggested that these isoforms directly regulate distinct gene subsets involved in inflammation and fibrosis. Mechanistically, estrogen receptor alpha (ESR1) indirectly activated PGR-A expression, potentially through recruitment of Forkhead box protein O1 (FOXO1) at the distal enhancer, suggesting a noncanonical, enhancer-mediated mechanism of PGR regulation. CONCLUSIONS: Distal enhancers regulate the PGR isoform balance and shape the progesterone-responsive transcriptome in human endometrial stromal cells. This enhancer-mediated mechanism expands current models of PGR regulation beyond promoter-level control and may offer potential therapeutic targets to restore normal progesterone responsiveness in conditions marked by PGR isoform imbalance.

Humans↗
PubMed1998

Evidence for enhanced ubiquitin-mediated proteolysis of the chicken progesterone receptor by progesterone.

Genomic actions of progesterone are mediated via A and B isoforms of the progesterone receptor (PR). One major factor controlling PR level is progesterone causing negative autoregulation (down-regulation) of the receptor protein. In this work we studied the mechanism whereby progesterone exerts its effects on PR level in the chicken oviduct. We found that progesterone does not markedly regulate PR mRNA expression. Furthermore, we demonstrate here for the first time that PR is a target for ubiquitylation and that the proportion of ubiquitylated PR is increased by progesterone treatment. Our data suggest that ligand-induced down-regulation of PR involves enhanced degradation of receptor protein by ubiquitin-proteasome system in vivo.

Amino Acid Sequence↗
PubMedDate not supplied

Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets.

Progesterone rapidly increased intracellular free calcium ([Ca2+]i) in human sperm, removal of extracellular Ca2+ prevented the increase in [Ca2+]i. The Ca2+ influx was not blocked by the T-type Ca2+ channel blocker mibefradil. However T-type calcium channels do appear to be present in human sperm because the neoglycoprotein mannose-albumin, an inducer of the acrosome reaction, was able to promote Ca2+ influx, which was blocked by mibefradil and more potently inhibited by Ni2+ than Cd2+. The receptor for progesterone that promotes the Ca2+ influx was located on the plasma membrane using FITC-progesterone-albumin. It is concluded that progesterone stimulates Ca2+ influx in human sperm via a unique Ca2+ channel possibly similar to a store-operated channel (SOC) or a receptor-operated channel (ROC). We have found that progesterone metabolites, such as pregnanolone and pregnanediol, promote a rapid rise in [Ca2+]i and aggregation in human platelets, similar to that observed with thrombin. The increase in [Ca2+]i was prevented when extracellular Ca2+ was removed or by the SOC inhibitor SKF-96365. The phospholipase C inhibitor U-73122 also prevented the increase in [Ca2+]i, suggesting that these metabolites interact with a cell surface receptor on the platelet to activate phospholipase C to produce inositol-P3, which mobilizes intracellular Ca2+, thereby activating the SOC in the plasma membrane. Progesterone and estradiol conjugated to albumin, also produced a rapid increase in [Ca2+]i, which was prevented by Ca2+ removal from the medium or when SKF-96365 or U-73122 were added. It is proposed that human platelets possess cell surface receptors for steroids.

Blood Platelets↗