Disease relevance of PGR

• Expression of this cDNA in Escherichia coli resulted in a protein exhibiting both PGR and LTB4 12-hydroxydehydrogenase activities [1].
• The s.c. administration of E3 to the pregnant guinea pig (1 mg/day per kg body weight for 3 days) provokes two biological responses in the fetal uterus: a uterothopic effect and a significant increase in the progesterone receptor [2].

High impact information on PGR

• In another series of experiments, it was demonstrated that tamoxifen or nafoxidine injected into the mother (1 mg/kg/day for 3 consecutive days) stimulates fetal uterine weight with an intensity similar to that of estradiol but, in contrast to estradiol, the stimulatory effect of the progesterone receptor is limited [3].
• Under conditions that favor the nuclear binding of progesterone, the sedimentation coefficient of the cytoplasmic progesterone receptor was 5.5 S [4].
• Binding of progesterone receptor by nuclear preparations of rabbit and guinea pig uterus [4].
• The cytoplasmic progesterone receptor had a sedimentation coefficient of 7 S when concentrated cytosol (20 mg of protein/ml) was incubated with progesterone at 0 degrees in 5 mM phosphate buffer [4].
• ADAMTS-1, a member of the A disintegrin and metalloproteinase family of proteases, is expressed in rodent follicles via progesterone receptor (PR)-dependent pathways [5].

Chemical compound and disease context of PGR

• In the newborn uterus (6-day old), tamoxifen (s.c. injection of 0.6 micrograms/g body weight) and estradiol (injection of 30 ng/g body weight) provoke a similar uterotrophic effect and both have a limited effect on the progesterone receptor [6].

Biological context of PGR

• Luteinizing hormone induces progesterone receptor gene expression in cultured porcine granulosa cells [7].
• There may be a cycloheximide-sensitive mechanism that modulates PR mRNA stability [7].
• This clone was regarded as part of the porcine PR cDNA because of its 98.3% and 95.7% homology to the hormone-binding domain of human PR cDNA in amino acid and nucleotide sequences, respectively [7].
• According to immunohistochemical assays, the binding assays for nuclear and cytosolic PR (PRn and PRc, respectively), by using [3H] R5020 at 4 degrees C for 15 h, also showed a higher specific binding during luteal phase [8].
• However, the PR mRNA in the oviduct, analyzed by RT-PCR, showed similar levels at both stages of the estrous cycle [8].

Anatomical context of PGR

• From our results we suspect that progesterone modulates ovarian function through LH-induced PR in granulosa cells [7].
• It is concluded that more than one progesterone receptor is present in porcine spermatozoa [9].
• However, a low expression of PR in the epithelium of the ampulla was observed [8].
• Although this methods could not be quantitative, indicate the possibility that a post-transcriptional control could differentially regulate the PR in the pig oviduct [8].
• The progesterone receptor (PGR) gene maps to porcine chromosome 9p13-p11 by a rodent-porcine somatic cell hybrid panel [10].

Associations of PGR with chemical compounds

• Basal and LH-induced PR mRNA levels were not affected by progesterone (100 ng/ml), estrogen (100 ng/ml), and RU 486 (10 ng/ml) at 3 h [7].
• The mechanism of the increased PR mRNA levels was studied in the presence of actinomycin-D and cycloheximide [7].
• However, the specific activity of PGR with 15-oxo-PGE1 as a substrate was approx. 300-fold that of LTB4 12-hydroxydehydrogenase [1].
• RU 486, a progesterone receptor antagonist, was used to investigate the effects of interruption of progesterone binding to its receptor on luteal function and gonadotropin secretion of pigs with aging corpora lutea [11].
• Progesterone receptor concentrations were inhibited to below basal levels by progesterone and R5020 and the nonsteroidal antiestrogens, tamoxifen, and 4-hydroxytamoxifen [12].

Physical interactions of PGR

• Progesterone production and progesterone receptor (PR) immunoreactivity in cumulus cells were not detected in porcine cumulus-oocyte complexes (COC) when observations were made either just after collection from the follicles or after 28 h cultivation without LH and FSH [13].
• A small proportion of progesterone receptor-containing perikarya in the medial preoptic area and the mediobasal hypothalamus were bound to be immunoreactive for galanin [14].

Regulatory relationships of PGR

• Insulin alone had no effect on progesterone receptor concentrations, but epidermal growth factor stimulated the progesterone receptor about as much as estradiol [12].
• FSH and LH induce progesterone production and progesterone receptor synthesis in cumulus cells: a requirement for meiotic resumption in porcine oocytes [13].

Other interactions of PGR

• This induction was mimicked by (Bu)2cAMP as well as by FSH and hCG, and the increased PR caused by LH and (Bu)2cAMP occurred in a dose-dependent manner [7].
• Results from this study provide strong evidence that the antagonistic effect of RU 486 on progesterone receptor results in an abrupt increase in PRL and progesterone secretion in hysterectomized gilts with aging corpora lutea [11].
• Down-regulated expression of A disintegrin and metalloproteinase with thrombospondin-like repeats-1 by progesterone receptor antagonist is associated with impaired expansion of porcine cumulus-oocyte complexes [5].
• In these studies, we evaluated the effect of PGF2alpha on luteal expression of receptors for progesterone (nuclear and membrane progesterone receptor [PR]), estradiol (ERalpha and ERbeta), glucocorticoid, androgens, and two enzymes in estradiol synthesis (P450-17alpha and aromatase) [15].
• Galanin varicosities appeared in close proximity to neurons with progesterone receptor-containing nuclei [14].

Analytical, diagnostic and therapeutic context of PGR

• In this study we used the RNase protection assay to evaluate the PR mRNA levels with a porcine cDNA clone isolated by the polymerase chain reaction (PCR) method [7].
• Moreover, progesterone receptor synthesis which is maintained when neonatal uteri are placed in organ culture conditions for 2 days was not affected by the 4-hydroxyandrostenedione treatment [16].
• A double-labeling immunofluorescence procedure was used to determine whether progesterone receptor (PR)-immunoreactive (IR) neurons in the preoptic area and hypothalamus of female guinea pigs also contained aromatic L-amino acid decarboxylase (AADC), an enzyme involved in the synthesis of both catecholamines and serotonin [17].
• Double-label immunocytochemistry has been employed to determine whether progesterone receptor (PR)-containing neurons in the arcuate nucleus (AR) of female guinea pig contain neuropeptide Y (NPY) [18].
• A putative non-genomic progesterone receptor was identified by Western blot analysis from the membrane fraction but not the cytosolic fraction of boar spermatozoa using monoclonal antibody (mAb) C-262 [19].

References