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 91 records · Page 5Linked to original sources
PubMed1992

Possible mechanisms for reduction of circulating concentrations of progesterone by interferon-alpha in cows: effects on hyperthermia, luteal cells, metabolism of progesterone and secretion of LH.

Experiments were performed to determine the mechanism by which recombinant bovine interferon-alpha I1 (rbIFN-alpha) causes an acute reduction in plasma concentrations of progesterone. In experiment 1, administration of a prostaglandin synthesis inhibitor blocked rbIFN-alpha-induced hyperthermia but did not prevent the decline in plasma concentrations of progesterone. The decline in progesterone concentrations caused by rbIFN-alpha was, therefore, not a direct consequence of the associated hyperthermia or of pathways mediated through prostaglandin synthesis. It is also unlikely that rbIFN-alpha acts to increase the clearance of progesterone since injection of rbIFN-alpha did not decrease plasma concentrations of progesterone in ovariectomized cows given an intravaginal implant of progesterone (experiment 2). In experiment 3, rbIFN-alpha did not affect basal and LH-induced release of progesterone from cultured luteal slices, indicating that rbIFN-alpha is unlikely to affect luteal function directly. Injection of rbIFN-alpha did, however, cause a decrease in plasma concentrations of LH in ovariectomized cows (experiment 4) that coincided temporally with the decrease in progesterone concentrations seen in cows having a functional corpus luteum. The present results strongly suggest that rbIFN-alpha acts to reduce secretion of progesterone by interfering with pituitary support for luteal synthesis of progesterone. The finding that rbIFN-alpha can inhibit LH secretion implies that interferon-alpha molecules should be considered among the cytokines that can regulate hypothalamic or pituitary function.

Animals↗
PubMed1993

Assessment of bioavailability of oral micronized progesterone using a salivary progesterone enzymeimmunoassay.

Salivary progesterone was measured sequentially by enzymeimmunoassay following 1 month and 6 months of oral therapy with 100 mg of micronized progesterone (MOP) in 40 healthy estrogenized postmenopausal women (aged 40-68 years). MOP was administered for 23 days every month. There were striking differences in the absorption of MOP between various subjects. Significant increases occurred in salivary progesterone concentrations over baseline and pretreatment levels and persisted for at least 10 h. Levels of salivary progesterone remained higher than pretreatment levels for at least 24 h after administration of MOP. Maximum mean concentrations of salivary progesterone of 827.2 and 888 pmol/l in the 1st and 6th months of therapy, respectively, were achieved within 2 h of administration and were above the 95th percentile of a control corridor which corresponds to the range found in the luteal phase. The areas under the salivary progesterone curve (AUC0-24 h, pmol/l) were 7177.75 and 7388.20 respectively, in the 1st and 6th months of therapy but the difference was not statistically significant. Serum and salivary progesterone peaked simultaneously and there was a significant correlation between the concentrations measured concurrently (y = 233.08 + 35.575x; r = 0.89, p < 0.001) thus supporting the current concept of a relatively rapid diffusion of steroids from plasma to saliva. Results of this study confirm those of previous investigations which monitored the bioavailability of MOP with the use of serum progesterone measurements and showed that luteal phase progesterone concentrations can be attained easily. The use of non-invasive salivary sampling and a cost-effective, direct enzymeimmunoassay showed a considerable advantage in the present study, compared with previous ones. We conclude that 100 mg MOP should be given at least twice-daily to maintain a stable physiological luteal phase level of progesterone during clinical hormone replacement therapy.

Administration, Oral↗
PubMed1975

[Metabolism of retro-progesterone and 17-hydroxy-retro-progesterone].

In comparative studes, the metabolism of retro-progesterone (9 beta,10alpha-pregn-4-ene-3, 20-dinoe) and 17-hydrozy-retro-progesterone (17-hydroxy-9 beta, 10 alpha-prgn-4-ene-3, 20-dione) as well as of progesterone and 17-hydroxy progesterone was investigated. The microsomal fraction from rat tests served as enzmye preparation. Whereas progesterone was metablised to 17-hydroxy-progesterone, testosterone and androstendion, retno-progesterone did not yield the corresponding reaction products. 16 alpha-Hydroxy-retro progresterone was found to be the main metabolite of retro-progesterone and identified by gas-liquid chromatopgray/mass spectrometry. In contrast to 17-hydroxy-progesterone, no transformation of 17-hudroxy-retro-progesterone to C19-steriods was observed. From these experiments, it can beconcluded that C21 -retro-steriods are not attacked by the 17alpha-hydrozylase and the C17-C20-desmolase of mammalian origin.

Androstenedione↗
PubMed1990

Progesterone production and clearance in cyclic ewes passively immunized against progesterone.

The effects of passive immunization of ewes against progesterone on plasma progesterone concentrations and on the metabolic clearance rate (MCR) and production rate (PR) of progesterone were investigated. Three treatment groups were studied: 1) nonimmunized controls, 2) ewes passively immunized with antiprogesterone serum, and 3) immunized progestagen-treated ewes, treated concomitantly with anti-serum and with a synthetic progestagen that is not bound by the antiserum. Progesterone levels in the immunized ewes reached a maximum of 27.7+/-4.8 nmol/l and were significantly higher (P<0.05) than in the nonimmunized controls (9.2+/-1.1 mol/l) or the immunized progestagen-treated ewes (15.6+/-1.6 nmol/l). Mean progesterone MCR in the immunized ewes was 1.6+/-0.5 and 2.1+/-0.3 liter/min on Days 7 and 13 of the estrous cycle, respectively, compared with 0.8+/-0.2 and 1.4+/-0.3 liter/min, respectively, in nonimmunized controls. The progesterone production rate in the immunized ewes was significantly higher than in nonimmunized controls, and reached 12.0+/-2.2 and 19.7+/-1.6 nmol/min on Days 7 and 13 of the estrous cycle, respectively, compared with 4.6+/-0.6 and 10.0+/-2.5 nmol/min in nonimmunized controls (P<0.03 for both comparisons). Treatment with progestagen had no significant effect on progesterone MCR or PR of immunized ewes. The LH pulse frequency on Days 10 to 11 of the cycle was 0.7+/-0.3, 1.8+/-0.3 and 0.0+/-0.0 pulses/6 h in the control, immunized and immunized progestagen-treated groups, respectively (P<0.05). It is concluded that the increased plasma progesterone levels in the immunized ewes are the result of an increased progesterone production rate, which may have been induced by an increase in gonadotrophin secretion or by a direct effect of the anti-progesterone serum on the ovary.

Journal Article↗
PubMed1994

Effect of induced suprabasal progesterone levels around estrus on plasma concentrations of progesterone, estradiol-17beta and LH in heifers.

A controlled study was carried out to investigate the effects of suprabasal plasma progesterone concentrations on blood plasma patterns of progesterone, LH and estradiol-17beta around estrus. Heifers were assigned to receive subcutaneous silicone implants containing 2.5 g (n=4), 5 g (n=4), 6 g (n=3), 7.5 g (n=3) or 10 g (n=4) of progesterone, or implants without hormone (controls, n=5). The implants were inserted on Day 8 of the cycle (Day 0=ovulation) and left in place for 17 d. The time of ovulation was determined by ultrasound scanning. Blood was collected daily from Days 0 to 14 and at 2 to 4-h intervals from Days 15 to 27. Control heifers had the lowest progesterone concentrations on Days 20.5 to 21 (0.5 +/- 0.1 nmol L(-1)); a similar pattern was observed in heifers treated with 2.5 and 5 g of progesterone. In the same period, mean progesterone concentrations in the heifers treated with 6, 7.5 and 10 g were larger (P < 0.05) than in the controls, remaining between 1 and 2.4 nmol L(-1) until implant removal. A preovulatory estradiol increase started on Days 16.4 to 18.4 in all the animals. In the controls and in heifers treated with 2.5 and 5 g of progesterone, estradiol peaked and was followed by the onset of an LH surge. In the remaining treatments, estradiol release was prolonged and increased (P < 0.05), while the LH peak was delayed (P < 0.05) until the end of the increase in estradiol concentration. The estrous cycle was consequently extended (P < 0.05). In all heifers, onset of the LH surge occurred when progesterone reached 0.4 to 1.2 nmol L(-1). The induction of suprabasal levels of progesterone after spontaneous luteolysis caused endocrine asynchronies similar to those observed in cases of repeat breeding. It is suggested that suprabasal concentrations of progesterone around estrus may be a cause of disturbances oestrus/ovulation.

Journal Article↗
PubMed1992

Proto-oncogene erbA expression and increased abundance of progesterone receptors in the mouse uterus after passive immunisation against progesterone before implantation.

Passive immunisation with a monoclonal anti-progesterone antibody (DB3) prevents pregnancy in the mouse, and antibody is localised in the endometrium before the onset of implantation. BALB/c female mice were injected intraperitoneally with 9 nmol of DB3 (a dose known to cause 100% infertility) 32 h post coitum, and the uterus was removed at various times after injection. Using a monoclonal anti-progesterone receptor antibody (PR6), expression of progesterone receptors was found to be abundant in uterine tissue of DB3-treated mice; this was associated with substantial progesterone receptor mRNA levels and with maximum localisation of DB3 antibody as detected by anti-idiotype antibody. Control animals treated with an equal amount of the mouse myeloma protein P3 showed very low levels of progesterone receptor in the uterus. DB3 treatment also affected uterine expression of the proto-oncogene erbA product (which shows primary sequence homology with the progesterone receptor) as revealed by specific antiserum to the ERBA protein and by in situ hybridisation with a cDNA probe to v-erbA. Time-course studies indicated that the erbA gene was expressed at a high level before progesterone receptor expression increased, that its expression was dependent on the presence of the embryo and that erbA expression persisted longer in DB3-treated females. The observations suggest that anti-progesterone immunisation has a direct effect within the uterus, involving persistence of proto-oncogene erbA expression (which itself may represent an early maternal response to pregnancy) and increased progesterone receptor levels resulting from an unopposed oestrogen effect derived from local ligand withdrawal.

Amino Acid Sequence↗
PubMed1982

Cytosol and nuclear progesterone-receptor concentrations in the rabbit endometrium during early pseudopregnancy under different treatments with estradiol and progesterone.

In an attempt to understand the mechanism of the antiprogestational action of estrogens during early pseudopregnancy we determined the cytosolic and nuclear concentrations of progesterone receptors in the endometrium of rabbits treated with hCG followed by various combinations of estradiol and progesterone. The progestational response of the endometrium was followed by quantitation of the uteroglobin content in the uterine lumen. In rabbits treated with hCG alone there was a clear progestational response (40% relative uteroglobin content), but only 16% of the progesterone receptors were located in the nucleus. After additional treatment with progesterone the progestational response remained high (45% relative uteroglobin content), the total cellular content of progesterone receptor increased, and 5% of the complexes were found in the nucleus. These findings suggest that a consumption of nuclear progesterone receptor is required for progestational action. Treatment of pseudopregnant rabbits with estradiol resulted in a marked increase not only of the total cellular progesterone receptor but also of the percentage of it located in the nucleus (35%). Concomitantly, the progestational response was markedly inhibited (5% relative uteroglobin content). These results confirm the relevance of nuclear consumption of progesterone receptor for progestational action, and suggest that some antiprogestational effects of estrogens may be due to their interference with the mechanism of progesterone receptor processing.

Animals↗
PubMed2005

Anesthetic effects of progesterone are undiminished in progesterone receptor knockout mice.

Progesterone has sedative and anesthetic effects but the underlying molecular mechanisms remain unclear. The two possible mechanisms by which progesterone affects the function of the brain include binding to intracellular progesterone receptors (PR) and metabolism to GABA(A) receptor-modulating neurosteroids. In this study, PR knockout (PRKO) mice were used as model to study the role of PRs in the anesthetic activity of progesterone. The progesterone-induced anesthetic activity was undiminished in female PRKO mice (ED50, 172 mg/kg) as compared to their wild-type littermates (ED50, 167 mg/kg). The progesterone-induced anesthetic activity was highly correlated with increased plasma allopregnanolone levels. Pretreatment of PRKO mice with the 5alpha-reductase inhibitor finasteride significantly reduced the progesterone-induced anesthetic activity. Allopregnanolone also evoked dose-dependent anesthetic activity in PRKO mice, which was similar to those of wild-type mice. Thus, the anesthetic activity of progesterone is not mediated by its interaction with PRs. The neurosteroid allopregnanolone partially mediates the anesthetic activity of progesterone by potentiation of GABA(A) receptor function.

Analysis of Variance↗
PubMed2003

Progesterone induces cellular differentiation in MDA-MB-231 breast cancer cells transfected with progesterone receptor complementary DNA.

Progesterone is an important regulator of growth and differentiation in breast tissues. In this study, the effect of progesterone on cell differentiation was evaluated in the estrogen receptor-negative and progesterone receptor (PR)-negative MDA-MB-231 cell line which was transfected with PR-complementary DNA. Morphological changes were analyzed at the ultrastructural level by scanning and transmission electron microscopy. Progesterone-treated PR-transfected cells exhibited a more protracted and well spread morphology with an increase in organelles such as mitochondria and rough endoplasmic reticulum as compared to the rounded form of control vehicle (0.1% ethanol)-treated PR-transfected cells. Vehicle and progesterone-treated MDA-MB-231 cells transfected with the pSG5 plasmid (transfection control cells) had similar rounded morphology as control vehicle-treated PR-transfected cells. Immunofluorescence staining revealed that expression of E-cadherin, a differentiation marker, was more prominent in progesterone-treated cells. Expression of keratin and vimentin but not beta-catenin was up-regulated in progesterone treated cells when evaluated by immunoblotting. As signal transducers and activators of transcription (STAT) molecules have been implicated in mammary differentiation, we analyzed the expression of Stat 1, 3, 5a, and 5b proteins and found a significant up-regulation of the Stat 5b protein in progesterone-treated cells. We have provided in vitro evidence of the close association of PR with differentiation in breast cancer. It is likely that the Stat 5b protein may play a major role in progesterone-induced differentiation in breast cancer cells.

Blotting, Western↗
PubMed1998

Progesterone-induced acrosome reaction in stallion spermatozoa is mediated by a plasma membrane progesterone receptor.

The aim of the present study was to investigate whether the induction of stallion sperm acrosome reaction (AR) by progesterone is mediated by binding of progesterone to a receptor on the sperm plasma membrane or to an intracellular progesterone receptor. Progesterone-BSA conjugate labeled with fluorescein isothiocyanate (P-BSA-FITC) in combination with a vital stain, ethidium homodimer, was applied to visualize the presence of the progesterone receptor on living spermatozoa. Alternatively, an indirect immunofluorescence technique employing a monoclonal antibody (C-262) against human intracellular progesterone receptor was conducted to validate the presence of the progesterone receptor. Immunogold labeling techniques enabled ultrastructural localization of P-BSA-FITC or C-262 with transmission electron microscopy. The dynamic changes in labeling patterns were monitored for sperm cells, using fluorescence microscopy and flow cytometry during a 5-h capacitation period. An increasing number of viable cells showed affinity for P-BSA-FITC or C-262 at the acrosomal plasma membrane region of the sperm head, while a decreasing number of viable cells were not labeled. In contrast, almost all deteriorated cells were labeled in the cytosol of the postequatorial region of the sperm head. Incubation with P-BSA-FITC resulted in the induction of AR but to a lesser extent than that for sperm incubated with free progesterone. Therefore, coupling of progesterone to its receptor on the sperm plasma membrane appears to be an important step in the induction of the AR.

Acrosome Reaction↗
PubMed1996

Binding of [3H]progesterone to the human progesterone receptor: differences between individual and mixed isoforms.

The human progesterone receptor (hPR) exists as two isoforms, hPR-A and hPR-B, which differ only in that hPR-A lacks 164 amino acids present at the amino-terminus of hPR-B. In this study we have separately expressed hPR-A and hPR-B and asked whether the progesterone-binding mechanisms are the same or different for the two forms of hPR and for their mixture. We investigated 1) the cooperativity of binding [3H]progesterone to the receptor, as measured by the Hill coefficient (nH); and 2) the dissociation rate of [3H]progesterone from the receptor. To compare the effects of dimerization, these ligand-binding properties were measured over a range of receptor concentrations. Binding of [3H]progesterone to hPR-A was positively cooperative at all concentrations used; the limiting value for the Hill coefficient was 1.47 +/- 0.11 at high receptor concentrations (5-19 nM) and 1.31 +/- 0.06 at low receptor concentrations (1-4 nM). Similarly, little change was observed in the dissociation rate constant over the same concentration range; the values at high and low concentrations were 4.59 +/- 0.15 and 3.03 +/- 0.25 x 10(-3) min-1, respectively. By contrast, the hPR-B concentration had a marked effect on positive cooperative binding and the dissociation rate of progesterone. At high hPR-B concentrations (3-5 nM), the limiting Hill coefficient was 1.49 +/- 0.11, which is indicative of moderately strong positive cooperativity, whereas at lower hPR-B concentrations (1-3 nM), the Hill coefficient was reduced to 1.1, which is essentially noncooperative. The [3H]progesterone dissociation rate was 4.52 +/- 0.44 x 10(-3) min-1 at the higher concentrations of hPR-B and was increased to 1.6 +/- 0.11 x 10(-3) min-1 at the lower concentrations. Thus, over the same concentration range where hPR-A exhibited no significant change in positive cooperativity or the dissociation rate, these progesterone-binding properties were highly dependent on the concentration of hPR-B. When hPR-A and hPR-B were mixed, positive cooperative binding and the dissociation rate were more similar to hPR-B than to hPR-A, in that both binding parameters were dependent on the concentration of receptor. However, the hPR-AB mixture differed from hPR-B alone in that the mixture required a greater receptor concentration (7-10 vs. 3-5 nM) to exhibit positive cooperativity and the increased dissociation rate. These results show, first, that each hPR isoform displays different [3H]progesterone-binding properties, which are most prominent at low concentrations of receptor, and second, that one isoform can influence the other. As the two receptor forms differ only at the N-terminus, yet positive cooperativity and changes in the dissociation rate constant are indicative of conformational changes affecting hormone binding, these results also strongly suggest that the N-terminus may directly or indirectly interact with the C-terminal ligand-binding domain.

Animals↗
PubMed2005

TIRF-based biosensor for sensitive detection of progesterone in milk based on ultra-sensitive progesterone detection in water.

We report on recent advances of our immunoassay for the hormone progesterone in cow's milk. Detection is based on total internal reflectance fluorescence (TIRF), the binding-inhibition assay with an immobilized progesterone derivative, and a commercially available monoclonal antibody to progesterone as biological recognition element. The fully automated River Analyzer (RIANA) biosensor for unattended, cost-effective, and continuous monitoring of environmental pollution therefore was adapted for sensitive determination of progesterone in milk. First, the sensitivity and robustness of the existing progesterone assay for water analysis were improved, resulting in a detection limit (LOD) of only 0.2 pg mL(-1) and a quantification limit (LOQ) of only 2.0 pg mL(-1). These extraordinary results are the lowest detection and quantification limits for progesterone determination using biosensors yet reported in the literature. Second, the accurate indicator of ovulation was calibrated and detected in three different types of milk (UHT milk, fresh milk, and raw milk). For commercial milk and randomly procured raw milk nominal levels of progesterone are typically in the range 5-15 ng mL(-1). Limits of detection (LOD) achieved for added progesterone (i.e. spiked samples) were between 45.5 and 56.1 pg mL(-1) depending on milk type. Having in mind the 1:10 dilution factor, these results are still a success. For the first time a commercially available antibody was incorporated into an immunoassay for progesterone detection in bovine milk, giving a detection limit below 1 ng mL(-1) for a fully automated biosensor. Thus the outstanding progress made with this biosensor in environmental monitoring and water analysis has now been successfully adapted to milk analysis for use in the field of reproduction management.

Animals↗
PubMed2006

Testosterone directly induces progesterone production and interacts with physiological concentrations of LH to increase granulosa cell progesterone production in laying hens (Gallus domesticus).

Blocking testosterone action with immunization or with a specific antagonist blocks the preovulatory surge of progesterone and ovulation in laying hens. Thus, testosterone may stimulate progesterone production in a paracrine fashion within the ovary. To test this hypothesis, we evaluated the effects of testosterone and its interaction with LH on the production of progesterone by granulosa cells in culture. Hen granulosa cells obtained from preovulatory follicles were cultured in 96 well plates. The effects of testosterone (0-100ng/ml) and/or LH (0-100ng/ml) were evaluated. LH-stimulated progesterone production in a dose response manner up to 10ng/ml (p<0.01). Testosterone, up to 10ng/ml, increased progesterone production in a dose response manner in the absence of LH and at all doses of LH up to 1ng/ml (p<0.001). However, at supraphysiological concentrations of LH (10 and 100ng/ml) there was no further increase in progesterone production caused by testosterone (p>0.05). Finally, the addition of 2-hydroxyflutamide (0-1000mug/ml) to hen granulosa cells cultured with 10ng/ml of testosterone reduced progesterone production in a dose response manner (p<0.001). In conclusion, testosterone stimulates progesterone production in preovulatory follicle granulosa cells and interacts with physiological concentrations of LH to increase progesterone production. In addition, testosterone stimulation on granulosa cells is specific since the testosterone antagonist decreased testosterone stimulatory action.

Animals↗
PubMed2004

Immunomodulatory and transcriptional effects of progesterone through progesterone A and B receptors in Hec50co poorly differentiated endometrial cancer cells.

OBJECTIVE: Derivatives of progesterone, progestins, are used to treat endometrial cancer; however, the pathways activated by the hormone have not been fully investigated. Progesterone acts through two receptor isoforms, progesterone receptors A and B (PRA and PRB), transcription factors that control the expression of downstream genes leading to endometrial differentiation. The purpose of this study was to perform an expression analysis to identify the mechanisms underlying progesterone's growth suppressive and immunomodulatory effects in endometrial cancer. METHODS: To study the molecular effects of progesterone, PRs were introduced into Hec50co cells. Expression array analyses followed by confirmatory semiquantitive reverse-transcriptase polymerase chain reaction (RT-PCR) experiments were performed. RESULTS: Expression analysis demonstrated a significant effect of progesterone after 12 hours of treatment on a number of genes, including cell signaling, DNA remodeling, apoptotic, tumor-suppressor, and transcription factors. Of particular interest was the consistent modulation of cytokines, which generally predicted for a powerful anti-inflammatory effect of progesterone through PR. Specifically, pro-inflammatory genes such as TNFalpha, IL-1beta, and MCP-1/MCAF-1 were down-regulated and anti-inflammatory genes such as TRAP1 and SMAD4 were induced. CONCLUSION: We have discovered that progesterone has a modulatory effect on inflammation and many other important cellular functions. These effects likely underlie the inhibitory effects of progesterone on tumor growth and invasion.

Cytokines↗
PubMed2003

The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21.

Human cytochrome P450c17 (17alpha-hydroxylase, 17,20-lyase) (CYP17) and cytochrome P450c21 (21-hydroxylase) (CYP21) differ by only 14 amino acids in length and share 29% amino acid identity. Both enzymes hydroxylate progesterone at carbon atoms that lie only 2.6A apart, but CYP17 also metabolizes other steroids and demonstrates additional catalytic activities. To probe the active site topologies of these related enzymes, we synthesized the enantiomer of progesterone and determined if ent-progesterone is a substrate or inhibitor of CYP17 and CYP21. Neither enzyme metabolizes ent-progesterone; however, ent-progesterone is a potent competitive inhibitor of CYP17 (K(I)=0.2 microM). The ent-progesterone forms a type I difference spectrum with CYP17, but molecular dynamics simulations suggest different binding orientations for progesterone and its enantiomer. The ent-progesterone also inhibits CYP21, with weaker affinity than for CYP17. We conclude that CYP17 accommodates the stereochemically unnatural ent-progesterone better than CYP21. Enantiomeric steroids can be used to probe steroid binding sites, and these compounds may be effective inhibitors of steroid biosynthesis.

Binding Sites↗
PubMed1999

Differential gene expression in progesterone-sensitive and progesterone-insensitive endometrial carcinoma cells.

High doses of progesterone are used in the treatment of advanced and recurrent endometrial cancer. Unfortunately the response rate is relatively low: 10-30%. The mechanisms involved in the development of insensitivity to progesterone treatment of endometrial cancer tissue are largely unknown. As tumour development is thought to be associated with a cascade of genetic alterations, it can be expected that genetic changes are involved in the development of progesterone insensitivity in endometrial carcinomas. We therefore started an investigation to identify, isolate and characterise progesterone-regulated genes involved in progesterone-induced growth inhibition in endometrial carcinoma cells. Using differential display PCR eight progesterone-regulated cDNA clones were identified in endometrial carcinoma cell lines. Four of these progesterone-regulated cDNA clones were regulated in the for growth progesterone-sensitive cell line IK-3H12 and not regulated in the for growth-insensitive cell line ECC-1. This indicates that these four cDNA clones represent potentially important genes, which could be involved in inhibition of growth of endometrial carcinoma tissue by progesterone.

Antineoplastic Agents↗
PubMed2002

Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity.

PROBLEM: Progesterone induced blocking factor (PIBF) is a mediator of progesterone that blocks peripheral blood lytic natural killer (NK) activity. Progesterone or PIBF stimulated decidual macrophages block up-regulation of perforin expression in decidual lymphocytes (DL). Therefore, we investigated whether progesterone regulates cytotoxicity of DL. METHOD OD STUDY: Decidual mononuclear cells were cultured with progesterone. PIBF, progesterone and anti-PIBF antibody or in the medium only. Cytolytic activity of non-adherent DL was measured by PKH-26 (red) 2 hr cytolytic assay and flow cytometry. Perforin positive DL were detected by immunofluorescency and PIBF-positive cells by immunohistology. RESULTS: Progesterone and PIBF, in a dose-dependent manner decreased cytotoxicity of DL against K-562 targets, and perforin egzocytosys was blocked. Anti-PIBF antibodies reversed the progesterone mediated reduction in cytolytic activity of DL. PIBF positive cells were found in first trimester pregnancy decidua. CONCLUSION: The results indicate possible role for PIBF, as a mediator of progesterone in regulation of DL cytolytic activity at the maternal-foetal (M-F) interface.

Biological Assay↗
PubMed1994

Differential control of immunoreactive alpha-inhibin and progesterone production by marmoset luteal cells in vitro: evidence for a paracrine action of alpha-inhibin on basal and gonadotropin-stimulated progesterone production.

There is an increase in plasma concentrations of immunoreactive (ir) inhibin unaccompanied by a rise in plasma progesterone during early pregnancy in the marmoset monkey. We investigated the potential involvement of hCG and prostaglandin E2 (PGE2) in stimulating a selective increase in inhibin concentrations by measuring the production of ir-alpha-inhibin and progesterone by dispersed luteal cells cultured under serum-free conditions. After one day, hCG had no effect on progesterone production by the cells but stimulated a significant increase (p < 0.05) in alpha-inhibin production. PGE2 significantly increased progesterone production (p < 0.001) but inhibited the production of alpha-inhibin (p < 0.001). After three days of culture, output of alpha-inhibin fell to low levels and no significant effect of hCG or PGE2 was detected. Progesterone also fell with time in culture, but hCG maintained production resulting in a significant increase above control levels (p < 0.001). The addition of low density lipoproteins (LDL) to the culture medium increased progesterone production (p < 0.001) while decreasing alpha-inhibin production (p < 0.01). Immunoneutralization of endogenous alpha-inhibin resulted in a significant decrease in both basal (p < 0.05) and gonadotropin-stimulated (p < 0.05) progesterone concentrations. These results provide further evidence for differential control of progesterone and alpha-inhibin production by marmoset luteal cells and show that hCG can selectively stimulate alpha-inhibin production. In addition, alpha-inhibin may have a local paracrine action in the marmoset CL, enhancing both basal and gonadotropin-stimulated progesterone secretion.

Animals↗