Disease relevance of Pgr

• The ER-mediated repression of the PR immunoreactivity was evidently restricted to the uterine epithelium, as we found that in the epithelial cells of the mammary gland and in cells of N-nitrosomethylurea-induced mammary carcinomas the PR expression was induced by estrogens and was blocked by the pure antiestrogen ZM 182780 [1].
• These compounds, unable to stimulate proliferation of uterine leiomyoma cells, did exhibit agonistic activity in these cells at the transcriptional level in the estrogen-sensitive reporter gene assay, and they were also able to upregulate PR message [2].
• The effects of ischemia on estrogen and progesterone receptor profiles in the rodent uterus [3].
• In MtT/F84, a pituitary tumor, which was established in our laboratory and has been maintained with in vivo passages, we investigated the PR regulation by E2 in relation to the host's thyroidal status [4].
• Androgen is suggested to act as a negative modulator of progesterone receptor levels, which might have clinical relevance in terms of hormone therapy of breast cancer [5].

Psychiatry related information on Pgr

• These data indicate that there is a downregulation of PR prepartum and suggest that this decrease may play a role in the disinhibition of maternal behavior at parturition [6].
• Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction [7].
• RU-486 delayed the latency period and decreased tumor incidence in animals exposed to MPA at 4 weeks after DMBA treatment, indicating that the progesterone receptor may be partially responsible for transmission of proliferative signals [8].
• The overall results suggest that estradiol and testosterone treatment during the postnatal critical period of sexual differentiation of the brain modifies the regulation of the PR mRNA and protein expression during early onset of maturity [9].

High impact information on Pgr

• To test these alternatives we introduced a progesterone-receptor expression plasmid into the rat hepatoma cell line Fto2B-3 which contains glucocorticoid receptor but is devoid of progesterone receptor [10].
• In tumors grown in intact female rats, both testosterone and dihydrotestosterone decreased progesterone receptor levels in a dose-dependent manner, and testosterone completely blocked the estradiol-induced increase in progesterone receptor levels in tumors from ovariectomized rats [5].
• In uterus, up to 5 mg dihydrotestosterone/kg did not affect progesterone receptor levels, and a dose of 5 mg/kg was also uterotropic [5].
• Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat [5].
• Neither dihydrotestosterone nor testosterone had any effect on basal levels of progesterone receptor in tumors from ovariectomized rats [5].

Chemical compound and disease context of Pgr

• Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea [11].
• Blockade of the estrogen induced increase in progesterone receptor caused by propylthiouracil, an anti-thyroid drug, in a transplantable pituitary tumor in rats [4].
• The progesterone receptor was increased at least eightfold in the mammary adenocarcinomas from ovariectomized rats that were treated with diethylstilbestrol for 6 days [12].
• The functionality of the estrogen receptor as determined by the effect of estrogen on progesterone receptor levels and the effect of tamoxifen on tumor growth has been examined in the R3327 Dunning rat prostate adenocarcinoma [13].
• The use of decapitation after either ether or ketamine anesthesia is appropriate for measuring ER and PR receptors in rat uteri [14].

Biological context of Pgr

• Neither progestins nor estradiol transactivated the corresponding transfected reporter genes, suggesting that endogenous PR and ERbeta are transcriptionally incompetent [15].
• Expression of progesterone receptor (PR) mRNA in granulosa cells of ovarian preovulatory follicles is induced by LH (1, 2) and is essential for ovulation (3) [16].
• These results indicate that phosphorylation and synthesis of some regulatory factor(s) other than or in addition to the estrogen receptor (ER) are essential for transactivation of the PR gene [16].
• Hormone induction of progesterone receptor (PR) messenger ribonucleic acid and activation of PR promoter regions in ovarian granulosa cells: evidence for a role of cyclic adenosine 3',5'-monophosphate but not estradiol [16].
• Results from this study suggest that upregulation of PR mRNA expression, likely mediated via ER beta action, is involved in the genesis of T+E2-induced dysplasia in this animal model [17].

Anatomical context of Pgr

• We show herein that E alone does not induce the expression of PR mRNA in preovulatory granulosa cells [16].
• Taken together, our results suggest that the proliferative response of uterine stromal cells to picomolar concentrations of progestins does not require direct transcriptional effects and is mediated by activation of the Erk1-2 and Akt signaling pathways via cross talk between PR and ERbeta [15].
• Using electrophoretic mobility shift assays, the consensus ERE was shown to bind ERbeta, the predominant subtype present in rat granulosa cells, and ERalpha, the predominant subtype present in luteal cells, whereas the putative ERE-like region (ERE3) of the proximal PR promoter did not bind either ER subtype [16].
• Upon progestin treatment PR translocated to the cell nucleus where it colocalized with activated Erk1-2 [15].
• By use of immunohistochemistry we studied the effects of estrogens on the PR levels in the individual cell types of the target organs uterus and breast [1].

Associations of Pgr with chemical compounds

• Although 17beta-estradiol (E) can induce PR mRNA and activate PR promoter-reporter constructs in other cell types, the effects of E in granulosa cells appear to be indirect [16].
• Induction of PR mRNA by forskolin is blocked by the A-kinase inhibitor H89 and cycloheximide but not by the E antagonist, ICI 164,384 [16].
• In this work, we determined the expression pattern and the hormonal regulation of progesterone receptor (PR) isoforms in the rat lung of ovariectomized female rats after estradiol (E2) and progesterone (P4) treatments [18].
• The expression of both PR isoforms in the lung at mRNA and at protein levels was up-regulated by E2 while P4 down-regulated it at mRNA level [18].
• Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined [19].

Physical interactions of Pgr

• Interestingly, this slow and gradual transcription rate increase of the endogenous PR gene did not parallel binding of E2 to ER, which was maximized within 30 min [20].
• Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord [21].
• These results show that progestins can directly modulate the growth of mammary cancer cells even in the absence of progesterone receptor by interacting on the glucocorticoid receptor [22].

Co-localisations of Pgr

• Progesterone receptor (PR) messenger RNA (mRNA) is concentrated in neurons of the preoptic area and other regions of the rat hypothalamus where it is colocalized with the estrogen receptor and regulated by changes in the steroid hormonal milieu [23].

Regulatory relationships of Pgr

• Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs [24].
• Together, these results indicated that membrane ER-mediated E2 inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases [25].
• Progesterone receptor mRNA was not detected in rat-1 cells and was induced by E2 in both rat-1 + ERalpha and rat-1 + ERbeta cells [26].
• Treatment of animals with estrogen induced PR expression in the ERalpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ERalpha expression [27].
• Together, these results suggest that CaT1 is regulated by P4 at diestrus via a PR-dependent pathway [28].

Other interactions of Pgr

• In the YTS, TEST activated gene transcription in the yeast containing the AR or PR [29].
• DPN alone had only a significant E-like effect on gonadectomy cells and IR-PR, but not on GnRH self-priming [30].
• Besides PCNA, GEN effects on the uterine mRNA expression of IGF-1, IGF-1R, Complement C3, estrogen receptor-alpha (ERalpha) and -beta (ERbeta), as well as progesterone receptor were investigated in intact and OVX co-treated animals [31].
• Drospirenone displayed high affinity to PR and MR and low binding to AR, similar to progesterone [32].
• ER and PRL-R were low but PgR increased significantly in the tumor of the tamoxifen-treated rats [33].

Analytical, diagnostic and therapeutic context of Pgr

• Western-blot analyses of the same tissue homogenates indicated changes in ER alpha and PR but not ER beta proteins [34].
• In the uteri of rats, ovariectomy induced a decrease in PR immunoreactivity within the myometrium and outer stromal cell layers [1].
• Female fetuses were prepared for real-time reverse-transcription polymerase chain reaction (RT-PCR) or immunohistochemistry for PR [35].
• We used RNA filter hybridization, a quantitative reverse transcription-polymerase chain reaction amplification assay, and in situ hybridization to detect PR mRNA in the rat ovary [36].
• We used the polymerase chain reaction to clone the steroid-binding domain of the rat PR from uterine cDNA and used this as a probe to isolate a larger cDNA from a rat placental cDNA library [36].

References