Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PROGESTERONE”

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 343 records · Page 19Linked to original sources
PubMed2000

The distribution of progesterone receptor immunoreactivity and mRNA in the preoptic area and hypothalamus of the ewe: upregulation of progesterone receptor mRNA in the mediobasal hypothalamus by oestrogen.

The distribution of progesterone receptors (PR) was mapped in the hypothalamus of the ewe using immunocytochemistry. These results were confirmed using in situ hybridization with a sheep-specific 35S-labelled riboprobe. In addition, the effect of oestrogen on the level of PR mRNA in the hypothalamus was examined in ovariectomized (OVX) ewes following treatment with an oestrogen implant or without treatment. PR immunoreactive (-ir) cells were readily detected in OVX animals. Labelled cells were observed in four main hypothalamic regions: the preoptic area (POA), including the organum vasculosum of the lamina terminalis, periventricular nucleus (PeVN), ventromedial nucleus (VMN) and the arcuate nucleus (ARC) (including the region ventral to the mamillary recess). In addition, lightly stained PR-ir cells were observed in the supraoptic nucleus and a few PR-ir cells were also found in the diagonal band of Broca. No PR-ir cells were found in the brainstem. PR mRNA-containing cells were found in the same hypothalamic regions as the PR-ir cells. Image analysis of emulsion-dipped slides following in situ hybridization indicated that oestrogen treatment increased (P<0.01) the mean number of silver grains/cell and the density of labelled cells in the VMN and ARC but had no effect on the level of PR mRNA expression in the POA or PeN. The distribution of PR-containing cells in the hypothalamus is similar to that described in other species and all cells were located in nuclei that contain large populations of oestrogen receptor-containing cells. These include regions implicated in the regulation of reproductive neuroendocrine function, and reproductive behaviour. Oestrogen and progesterone synergize to inhibit GnRH secretion and the present results suggest that these functions may involve cells of the VMN and ARC, with oestrogen acting to upregulate PR.

Animals↗
PubMed1985

Progesterone, 17-OH-progesterone, androstenedione and testosterone plasma levels in spermatic venous blood of normal men and varicocele patients.

Progesterone (P), 17-OH-progesterone (17-OH-P), Androstenedione (delta 4) and testosterone (T) plasma levels were measured in spermatic venous blood of twenty-nine varicocele patients (V) and in twelve normal subjects (N). Our data reveal a significant decrease of the mean testosterone in the spermatic blood of varicocele patients with respect to normal controls: (N = 1708.7 +/- 223.8 (SEM) nmol/l, n = 10. V = 1190.9 +/- 101.1 (SEM) nmol/l, n = 29. P less than 0.03). An inverse correlation has been observed between the age of varicocele patients and 17-OH-P (n = 29. y = -33.38x + 1384.70, r = -0.59, P less than 0.01) and delta 4 values (n = 23, y = -1.62x + 85.65, r = -0.49, P less than 0.05). The 17-OH-P/delta 4 ratio appears significantly augmented in varicocele patients with respect to normal controls (n = 4.80 +/- 0.86 (SEM), n = 12. V = 9.65 +/- 1.21 (SEM), n = 23.0.02 greater than P greater than 0.01). This indicates a deficiency in varicocele patients of 17-20 lyase activity. The positive correlation between the P/17-OH-P ratio and age of varicocele patients (n = 28, y = 0.007 x -0.090, r = 0.45, P less than 0.03) suggests a progressive impairment of 17-alpha-hydroxylase in such patients as they grow relatively older. These data demonstrated that the reduced spermatic levels of testosterone in varicoceles are due to the enzymatic impairment of testosterone biosynthesis, concerning firstly 17-20 lyase activity and secondly 17-alpha-hydroxylase activity. The latter enzymatic impairment is age related as is seen from the significant increase of the P/17-OH-P ratio in older patients.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Variant progesterone receptor mRNAs are co-expressed with the wild-type progesterone receptor mRNA in human endometrium during all phases of the menstrual cycle.

Progesterone receptor (PR) variant mRNAs in human endometrium could encode proteins with the potential to alter progesterone action in states of normal and abnormal endometrial development. We have assessed the expression levels of mRNA for the wild-type PR and splice variants of PR mRNA lacking exon 4 (del-4 PR), exon 6 (del-6 PR), exons 4 and 6 (del-4&6 PR), and part of exon 4 (del-p4 PR) or part of exon 6 (del-p6 PR) in the human endometrium throughout menstrual cycle development. Eighty-eight endometrial specimens (47 proliferative, 41 secretory) were collected from patients undergoing hysterectomy for benign gynaecologic causes. Measurements by RT-PCR indicated that mRNAs for wild-type PR, and splice variants del-4 PR, del-6 PR, del-4&6 PR, del-p6 PR, and a novel del-p4 PR were detected in all endometrial specimens throughout the menstrual cycle. Higher levels of wild-type PR and all PR variant mRNAs were found in the early and mid-proliferative endometrial phases than in secretory endometrium. The relative expression of mRNA for all PR variants compared to wild-type PR mRNA, however, did not change through all stages of endometrial development. We, therefore, found no evidence of differential co-expression of the PR variants compared with wild-type PR during normal menstrual development. Future studies will determine if the expression profile of PR variant mRNAs will be different in the endometrium of patients with infertility, recurrent pregnancy loss, or endometrial adenocarcinoma.

Alternative Splicing↗
PubMed1985

The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: I. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis.

Progesterone-treated lymphocytes (generator lymphocytes) of healthy pregnant women release a nondialyzable factor that inhibits both cytotoxic activity and prostaglandin F2 alpha synthesis of test lymphocytes. Production of this factor is blocked by protein synthesis inhibitors (cycloheximide and actinomycin D). Sodium dodecylsulfate polyacrylamide electrophoresis of the partially purified material revealed a main 34,000 MW protein band. Progesterone-treated lymphocytes of pregnant women showing clinical symptoms of threatened preterm delivery (risk group) failed to release this substance.

Cells, Cultured↗
PubMed1997

Expression of an immunomodulatory protein known as progesterone induced blocking factor (PIBF) does not correlate with first trimester spontaneous abortions in progesterone supplemented women.

PROBLEM: An immunomodulatory protein known as the progesterone induced blocking factor (PIBF) has been found to positively correlate with early pregnancy beta human chorionic gonadotropin (B-hCG) levels. The study presented herein evaluated PIBF levels from conception to the end of the first trimester to determine if lower levels will correlate with first trimester spontaneous abortions (SAB). METHOD: Progesterone induced blocking factor expression by lymphocytes measured using an immunocytochemistry method was compared in pregnant women with ongoing vs. failed pregnancies. RESULTS: There were no differences in the proportion of women having lymphocytes expressing PIBF or in the median numbers when comparing ongoing vs. failed pregnancies. There was no B-hCG interval where failed pregnancies were found to have lower frequency of PIBF expressing lymphocytes. CONCLUSION: Inadequate PIBF expression independent of low P levels does not appear to be an etiologic factor for first trimester SABs; thus measuring this protein in pregnant women lacks practical usefulness.

Abortion, Spontaneous↗
PubMed2005

Cyclin-dependent kinase activity is required for progesterone receptor function: novel role for cyclin A/Cdk2 as a progesterone receptor coactivator.

Our studies examining the role of the cell cycle-regulated kinase cyclin A/Cdk2 in progesterone receptor (PR) action have demonstrated that cyclin-dependent kinase activity is required for PR function and that cyclin A/Cdk2 functions as a PR coactivator. Although Cdk2 can phosphorylate PR, elimination of these phosphorylation sites has little effect on the ability of cyclin A/Cdk2 to stimulate PR activity. PR interacts with cyclin A and recruits cyclin A/Cdk2 to progestin-responsive promoters, stimulating transcription. Inhibition of Cdk2 activity abolishes progesterone-dependent activation of PR target genes in part through inhibition of PR-dependent recruitment of steroid receptor coactivator 1 (SRC-1) and subsequent histone H4 acetylation at the target promoter. In vitro studies revealed that the interaction between SRC-1 and PR is dependent upon phosphorylation of SRC-1. This heretofore-unknown mechanism provides a potential means for integrating the regulation of PR activity with cell cycle progression. Moreover, the ability of PR to recruit cyclin A/Cdk2 to target promoters provides locally elevated levels of kinase, which can preferentially facilitate phosphorylation-dependent interactions and enzymatic activities of coactivators at the target promoter.

Acetylation↗
PubMed2002

Expression and transcriptional activity of progesterone receptor A and progesterone receptor B in mammalian cells.

Progesterone is an essential regulator of normal female reproductive function. Its effects are mediated by two nuclear progesterone receptor (PR) proteins, PRA and PRB, which are identical except for an additional 164 amino acids at the N-terminal end of PRB. Transcriptional analyses of the two receptor forms have assigned strikingly distinct functional signatures to the two PRs, despite their apparent physical similarity. The basis of these differences is yet to be fully understood. Furthermore, these differences are strongly influenced by the cell type and the promoter used. We review the mammalian transcriptional studies of PRA and PRB, and compare them with what is known about their expression and function in target tissues.

Biomarkers, Tumor↗
PubMed2003

Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer.

Although interactions between estrogen and growth factor signaling pathways have been studied extensively, how growth factors and progesterone regulate each other is less clear. In this study, we found that IGF-I sharply lowers progesterone receptor (PR) mRNA and protein levels in breast cancer cells. Other growth factors, such as epidermal growth factor, also showed the same effect. The decrease of PR levels was associated with reduced PR activity. Unlike progestins, IGF-I does not utilize the proteasome for down-regulating PR. Instead, the IGF-I-mediated decrease in PR levels is via an inhibition of PR gene transcription. In addition, the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was found to be specifically involved in this IGF-I effect. Our data also suggest that the IGF-I down-regulation of PR is not mediated via a reduction of estrogen receptor (ER) levels or activity. First, IGF-I induced ligand-independent ER activity while reducing ER-dependent PR levels. Second, whereas PR and cyclin D1 are both ER up-regulated, IGF-I increased cyclin D1 levels while decreasing PR levels. Third, constitutively active PI3K or Akt induced ER activity but reduced PR levels and activity. Taken together, our data indicate that IGF-I inhibits PR expression in breast cancer cells via the PI3K/Akt/mTOR pathway. Because low or absent PR in primary breast cancer is associated with poor prognosis and response to hormone therapy, our results suggest that low PR status may serve as an indicator of activated growth factor signaling in breast tumor cells, and therefore of an aggressive tumor phenotype and resistance against hormonal therapy.

Breast Neoplasms↗
PubMed1980

Relationship between the changes in cytoplasmic progesterone receptor concentration and in nuclear progesterone binding sites in the hen hypothalamus and pituitary during the ovulatory cycle.

The amount of specific [3H]-progesterone bindings was measured in cytosols and in nuclear fractions of the hen hypothalamus and pituitary during the ovulatory cycle. In both tissues, a decrease in cytosol binding from the peak at 18 and 8 hr before ovulation was coincident with an increase in nuclear binding attained a peak 14 to 6 hr before ovulation. The results suggest that progesterone may act on the hypothalamus and pituitary 18-14 hr before ovulation and 8-6 hr before ovulation.

Animals↗
PubMed1994

Effect of melengestrol acetate (MGA) or progesterone-releasing intravaginal device (PRID) on follicular development, concentrations of estradiol-17 beta and progesterone, and luteinizing hormone release during an artificially lengthened bovine estrous cycle.

Two trials were conducted to determine whether 7-d progestogen treatment beginning on d 17 of the estrous cycle altered 1) ovarian follicular development, 2) serum concentration of estradiol-17 beta (E2) and progesterone (P4), and 3) patterns of release of luteinizing hormone (LH). In both trials, Angus, Angus x Holstein, or Holstein cows 2 to 6 yr of age were randomly assigned to receive either melengestrol acetate (MGA, .5 mg.animal-1.d-1; n = 23), a progesterone-releaseing intravaginal device (PRID, n = 26) or to serve as untreated Controls (n = 14). Ultrasonography and blood sampling were performed daily throughout the experiment beginning on d 3 (Trial 1) or d 9 (Trial 2) of the estrous cycle. In Trial 2, blood samples were collected every 15-min for 6 h on d 17 (all cows) and d 20 and 23 (MGA and PRID cows) for determination of LH. Estrous cycle length was 3 to 5 d greater (P < .05) for MGA- and PRID-treated cows characterized by two (MGA-2 and PRID-2) or three (MGA-3 and PRID-3) dominant follicles than for control cows exhibiting two (Control-2) or three (Control-3) dominant follicles. A greater proportion (P < .05) of MGA- than of PRID-treated cows ovulated the follicle that was dominant at the beginning of treatment on d 17 (10 of 23 vs 1 of 26). Serum P4 concentrations declined 3 d earlier in Control-2 and MGA-2 cows than in Control-3, MGA-3 or PRID-3 cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal↗
PubMed2003

Concentrations of progesterone in milk of cows administered an intravaginal progesterone insert.

Milk from pregnant cows contains concentrations of progesterone (P4) considered safe for human consumption. The objective of this study was to determine if concentrations of P4 in milk during administration of an intravaginal progesterone insert (CIDR insert) are less than concentrations of P4 in milk associated with pregnancy. Results have implications for human use of milk from cows receiving CIDR inserts. Holstein cows (N = 64; > 40 and < 150 d after calving) were administered 25 mg of PGF2alpha i.m. (study d 0) and 20 cows detected in estrus from 2 to 4 d later were assigned randomly to either control (N = 10; no further treatment) or CIDR insert (N = 10; 1.38 g of P4) inserted on study d 17 (14 +/- 1 d after estrus) and removed 7 d later. Composite milk samples were collected contemporaneously from each of the 20 estrous cycling cows and from 10 pregnant cows (> or = 60 and < or = 220 d of gestation) twice daily from study d 17 to 27. Concentrations of P4 in defatted milk samples were quantified using a validated radioimmunoassay. Mean logs of areas under the curve of concentrations of P4 from the afternoon on study d 17 through the afternoon on study d 27 were 3.05 ng day/ml for control, 3.33 ng day/ml for CIDR insert, and 3.81 ng day/ml for pregnant cows. Therefore, increased P4 due to pregnancy was 0.76 ng day/ml (3.81-3.05), whereas the increase in P4 due to CIDR insert was only 0.28 ng day/ml (3.33-3.05). Applying a 95% confidence interval to 0.28 ng day/ml provided an upper value of 0.70 ng day/ml, lower than the increase due to pregnancy. Because milk from pregnant cows is considered safe for human consumption, it follows that milk from cows administered CIDR inserts should also be considered safe, based on concentrations of P4.

Administration, Intravaginal↗
PubMed1991

Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies.

Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti-DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence and structural comparisons suggest that residues associated with VH CDR3 and VL CDR3 may have a key role in determining the efficiency of anti-idiotypic immunization against progesterone. The variability in outcome of using anti-idiotypic reagents against a defined panel of related antibodies is relevant to the use of anti-idiotypes as surrogate antigens.

Amino Acid Sequence↗
PubMed1994

Effects of intrahypothalamic administration of antisense DNA for progesterone receptor mRNA on reproductive behavior and progesterone receptor immunoreactivity in female rat.

Since reproductive behaviors of female rats can be correlated with estrogen-induced increases in progestin binding by hypothalamic neurons, we hypothesized that specific progesterone receptor (PR) antisense DNA sequences might decrease these behaviors. Antisense oligonucleotides (15 bases), spanning the translation start site of rabbit PR mRNA, were microinjected directly among ventromedial hypothalamic neurons, and their behavioral effects were compared to control oligonucleotides composed of the same nucleotide bases in scrambled order. When applied 12 but not 24 hr after estradiol, the PR antisense treatment significantly reduced iordosis behavior, measured either as a reflex or in a mating behavior test. Notably, proceptive behaviors, which are strongly progesterone dependent, were greatly reduced in their occurrence (80% decrease). To see if PR protein was also reduced, antisense DNA was administered near the ventromedial hypothalamus on one side of the brain, while the other side received the scrambled control sequence or vehicle. The total number of PR-immunoreactive cells on the antisense side was significantly lower in the ventromedial nucleus, but not in control measurements from the medial preoptic area. Interrupting gene expression for PR, a transcription factor, in hypothalamic neurons, can have behavioral and immunocytochemical effects.

Animals↗
PubMed1997

A 361 base pair region of the rat FSH-beta promoter contains multiple progesterone receptor-binding sequences and confers progesterone responsiveness.

The rat is frequently used as a model to study the role of progesterone (P) in regulating FSH secretion and synthesis. The ability of P to modulate rat FSH-beta mRNA levels suggests the presence of a functional hormone response element. We have found three PRE-like sequences upstream of the transcription start site in the rat FSH-beta gene. These sequences are herein referred to as PRE-like sequence #1, #2 and #3 with #1 being most distal from the start site. The current studies determined whether these PRE-like sequences bound P receptor (PR) and were functional in regulating the induction of expression by P. Electrophoretic mobility shift assays (EMSA) demonstrated that a single 289 base pair (bp) DNA fragment encompassing all three PRE-like sequences specifically bound PR. Further, PR bound with high affinity to double-stranded oligonucleotides representing individual PRE-like sequences #1, #2 and, with lower affinity to a double-stranded oligonucleotide representing PRE-like sequence, #3. We have cloned a 361 bp sequence from the promoter region of the rat FSH-beta gene encompassing all three PRE-like sequences into a luciferase reporter vector (pGL3-promoter) yielding pFSHbeta361-luc+ which when transiently transfected into primary rat pituitary cell cultures, conferred P-responsiveness to a heterologous promoter. P-responsiveness was dependent upon the presence of PR and was blocked by the PR antagonist RU-486. These data strongly suggest the presence of functional PRE's in the rat FSH-beta gene promoter.

Animals↗
PubMed1984

Estrus and ovulation in beef cows following use of progesterone-releasing devices, progesterone and estradiol valerate.

Two hundred nonsuckling beef cows were treated with either 1) a progesterone-releasing intravaginal device (PRID) for 12 days; 2) PRID plus an IM injection of 200 mg progesterone (PRID-P); 3) PRID plus 5-mg IM injection of estradiol valerate (PRID-EV); or 4) PRID-EV-P. Cows were started on treatment on one of the first eight days of the estrous cycle. The number of cows which had P levels above 1 ng/ml one day after PRID removal was 12 to 50% lower in PRID-EV and PRID-EV-P groups than in PRID and PRID-P groups (P < 0.05). The proportion of cows showing estrus by 96 hours after PRID removal was 38, 36, 77, and 88% (P < 0.05) for the PRID, PRID-P, PRID-EV and PRID-EV-P groups, respectively. Thirty-one percent fewer cows treated with PRID on days 5 through 8 of the estrous cycle showed estrus by four days after PRID removal than those treated on days 1 through 4. In addition, 18 to 22% more cows had P levels above 1 ng/ml among cows treated with PRID or PRID-P on days 5 through 8 than among cows treated similarly on days 1 through 4. It was concluded that effective synchronization of estrus is achieved only when estrogen is used in conjunction with PRID in cows treated for twelve days during the first eight days of an estrous cycle.

Journal Article↗
PubMed1988

Radioimmunoassay and enzymeimmunoassay of plasma progesterone as monitors of progesterone sponge treatment in ewes.

The daily plasma progesterone (P) concentrations achieved during insertion of P (750 mg) sponges into two groups of ewes were examined. Group I received prostaglandin (PG) treatment, which was required to suppress the P production (to levels of < 0.3 ng hormone/ml plasma) from the corpora lutea (CL) of a previous superovulation treatment, following which these Group I ewes and the anestrous Group II ewes were sponge treated. Radioimmunoassay (RIA) and enzymeimmunoassay (EIA) were used to measure the P levels in both groups. Progesterone (750 mg) sponges with and without citric acid impregnation were inserted into all the ewes for 12 days (d). Citric acid lowered the P levels reaching the plasma from the sponges, but it did not mask the characteristic profile (during the treatments) determined by the states of the ewes (single PG and double PG injected, Group I or in the anestrous Group II). The plasma P levels in Group I and II ewes rose to at least 7.0 ng/ml at intervals during treatment. The duration and magnitude of the P concentrations in the plasma were higher in the single PG compared with the double PG ewes during sponge insertion in Group I. The anestrous Group II ewes showed two major peaks (Day 1, P<0.01 and Days 11 to 12, P<0.05) during sponge treatment. A P level > 2.0 ng/ml was maintained over the entire treatment in the single PG and in the anestrous hormone-treated ewes, and was of shorter duration (7 d) in the double PG-treated animals. These endogenous patterns in P profiles of the ewes indicate that the hormone level during sponge insertion varies in magnitude and duration, parameters determined by the physiological/endocrinological state of the ewes at the start of the treatment. The EIA correlated significantly (P<0.001) with the RIA for the measurement of P concentration, when analyzed daily on an individual animal basis.

Journal Article↗
PubMed2002

The temporal reliability of serum estrogens, progesterone, gonadotropins, SHBG and urinary estrogen and progesterone metabolites in premenopausal women.

BACKGROUND: There is little existing research to guide researchers in estimating the minimum number of measurement occasions required to obtain reliable estimates of serum estrogens, progesterone, gonadotropins, sex hormone-binding globulin (SHBG), and urinary estrogen and progesterone metabolites in premenopausal women. METHODS: Using data from a longitudinal study of 34 women with a mean age of 42.3 years (SD = 2.6), we calculated the minimum number of measurement occasions required to obtain reliable estimates of 12 analytes (8 in blood, 4 in urine). Five samples were obtained over 1 year: at baseline, and after 1, 3, 6, and 12 months. We also calculated the percent of true variance accounted for by a single measurement and intraclass correlation coefficients (ICC) between measurement occasions. RESULTS: Only 2 of the 12 analytes we examined, SHBG and estrone sulfate (E1S), could be adequately estimated by a single measurement using a minimum reliability standard of having the potential to account for 64% of true variance. Other analytes required from 2 to 12 occasions to account for 81% of the true variance, and 2 to 5 occasions to account for 64% of true variance. ICCs ranged from 0.33 for estradiol (E2) to 0.88 for SHBG. Percent of true variance accounted for by single measurements ranged from 29% for luteinizing hormone (LH) to 92% for SHBG. CONCLUSIONS: Experimental designs that take the natural variability of these analytes into account by obtaining measurements on a sufficient number of occasions will be rewarded with increased power and accuracy.

Journal Article↗