Disease relevance of AKR1C1

• The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog rho-crystallin, and bovine lung prostaglandin F synthase (reductase) [1].
• A lung type prostaglandin F synthase is expressed in bovine liver: cDNA sequence and expression in E. coli [2].
• Pertussis toxin treatment of bovine parathyroid cells reduced the PGF2 alpha inhibition [3].
• 3 Slow reacting substance of anaphylaxis (SRS-A), prostaglandin F2 alpha (PGF2 alpha) and PGE2 were spasmogenic, whereas PGE1 caused relaxation [4].
• The quantities of PGE-2, PGFM and PGF-2 alpha recovered in uterine flushings taken from heifers on Day 18 were greater in pregnant than other animals (P less than 0.01, P less than 0.05, P less than 0.001, respectively) [5].

Psychiatry related information on AKR1C1

• Thus, individual differences in uterine secretion of PGF2 alpha in response to oxytocin were related to stage of the cycle and to differences in the endogenous ovarian steroid environment within each stage of the estrous cycle [6].

High impact information on AKR1C1

• Nucleotide-sequence analyses of cloned cDNA inserts have revealed that PGF synthase consists of a 969-base pair open reading frame coding for a 323-amino acid polypeptide with a Mr of 36,666 [7].
• The present studies were conducted to determine whether prostaglandin F2 alpha (PGF2 alpha) stimulates the production of "second messengers" derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ([Ca2+]i) in isolated bovine luteal cells [8].
• In addition, PGF2 alpha increased inositol phospholipid turnover, as evidenced by increased 32PO4 incorporation into phosphatidic acid and phosphatidylinositol [8].
• These findings demonstrate that the action of PGF2 alpha is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum [8].
• Stereospecific conversion of prostaglandin D2 to (5Z,13E)-(15S)-9 alpha-11 beta,15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-prostaglandin F2) and of prostaglandin H2 to prostaglandin F2 alpha by bovine lung prostaglandin F synthase [9].

Chemical compound and disease context of AKR1C1

• Dispersed bovine parathyroid cells treated with or without 0.5 micrograms/ml pertussis toxin were tested with stimulatory (epinephrine, isoproterenol) or inhibitory (PGF2 alpha) agonists for responses in cAMP accumulation (5-min incubation) or PTH (90-min incubation) release [3].
• Concentrations of prostaglandin F2 alpha (PGF2 alpha) and thromboxane B2 (TXB2) were evaluated in the milk of cows with naturally occurring (n = 3) and experimentally induced (n = 5) acute coliform mastitis [10].
• The PGF2 alpha appears to regress the luteinized ovarian cysts and cows exhibit estrus 2 to 3 d after PGF2 alpha treatment (11 to 12 d after GnRH) [11].
• Baseline adenocarcinoma production of PGF2 alpha was 117.5 pmol/10(6) cells and fell to 24.2 pmol/10(6) cells hours following incubation with indomethacin [12].
• Clinical endometritis at post-partum examination did not influence progesterone levels after treatment with PGF2 alpha [13].

Biological context of AKR1C1

• Moreover, the amino acid sequence of the liver-type PGF synthase was identical with that of bovine liver DD3 [14].
• cDNA cloning, expression, and mutagenesis study of liver-type prostaglandin F synthase [14].
• Using the cDNA of bovine lung prostaglandin F synthase (EC 1.1.1.2) as a probe, we isolated a clone from a bovine liver cDNA library which differed in only eleven nucleotides from the probe [2].
• Thus, significant overexpression of a human aldo-keto reductase structurally related to bovine prostaglandin F synthase may result from exposure of cells to Michael reaction acceptors and may give rise to an enhanced capacity to metabolize exogenous and endogenous substrates, thereby contributing to the drug-resistant phenotype [15].
• These data indicate that apoptosis occurs during both spontaneous and PGF2 alpha-induced luteal regression in cattle; however, apoptosis, as indicated by oligonucleosome formation, is not apparent until after serum progesterone concentrations have begun to decrease.(ABSTRACT TRUNCATED AT 400 WORDS)[16]

Anatomical context of AKR1C1

• Our objective was to identify which prostaglandin F synthase is involved and to study its regulation in the endometrium and in endometrial primary cell cultures [17].
• The liver-type PGF synthase was expressed in COS-7 cells, and its recombinant enzyme had almost the same properties as the native enzyme [14].
• Activated neutrophils did not alter 6-keto PGF1 alpha production [18].
• In parallel, DMTU also decreased PMA and neutrophil-mediated PGF1 alpha increases in supernatants from endothelial cell monolayers [19].
• Selective removal of the BRA endothelium (by gassing the BRA lumen, checked by scanning electron microscopy) blocked the relaxation caused by ACh of PGF2 alpha-induced contractions and unmasked a constricting action of ACh [20].

Associations of AKR1C1 with chemical compounds

• PGF synthase has at least two isoforms, the lung-type enzyme (Km value of 120 microM for PGD2 (Watanabe, K., Yoshida, R., Shimizu, T., and Hayaishi, O [14].
• Prostaglandin (PG) F synthase catalyzes the reduction of PGD2 to 9alpha,11beta-PGF2 and that of PGH2 to PGF2alpha on the same molecule [14].
• The sequence data presented suggests that 3 alpha-HSD, prostaglandin F synthase, and aldehyde/aldose reductases are members of a common gene family [21].
• However, the binding constant for NADPH of the liver enzyme was 3.5 fold higher than that of lung prostaglandin F synthase [2].
• The high relative activity against prostaglandin H2 in combination with a high Km value for prostaglandin D2 identified this liver enzyme as a lung type prostaglandin F synthase [2].

Physical interactions of AKR1C1

• Oxytocin then binds to its endometrial receptors and initiates luteolytic pulses of PGF-2 alpha [22].

Regulatory relationships of AKR1C1

• Conceptuses of sheep and cattle produce proteins which, when introduced into the uterine lumen of nonpregnant ewes and cows, suppress the ability of oestradiol and oxytocin to stimulate uterine production of PGF-2 alpha [23].
• Twice daily i.m. injections of PGF-2 alpha on Days 3 and 4 of the bovine oestrous cycle inhibited progesterone secretion by the corpus luteum and induced precocious oestrus [24].

Other interactions of AKR1C1

• The amino acid sequence of rat liver 3 alpha-HSD bears no significant homology with 3 beta-, 17 beta- or 11 beta-hydroxysteroid dehydrogenases but has striking homology with bovine lung prostaglandin F synthase (69% homology at the amino acid level and 74% homology at the nucleotide level) which is a member of the aldehyde/aldose reductase family [21].
• Regulation of cyclooxygenase-2 and prostaglandin F synthase gene expression by steroid hormones and interferon-tau in bovine endometrial cells [25].
• These results show that, under the influence of progesterone, oestradiol enhances the oxytocin-induced release of PGF-2 alpha, and suggest a possible synergistic action of these hormones for the induction of luteolysis in heifers [26].
• Lifespan of the first corpus luteum formed in post-partum PGF-2 alpha-immunized cows was short (less than 10 days; N = 1), normal (mean = 22 days; N = 4) or maintained (greater than 31 days; N = 5) [27].
• Lavendustin A (0.001-1 microg/ml) increased IGF-I release by bovine (but not by porcine) granulosa cells, cAMP release by bovine granulosa cells, and PGF-2 alpha output by porcine ovarian follicles (at 10 microg/ml) [28].

Analytical, diagnostic and therapeutic context of AKR1C1

• Measurements of endogenous prostaglandin production by radioimmunoassay demonstrated that PGE2 was the major arachidonic acid metabolite released, with smaller amounts of PGF2 alpha and the stable hydrolysis product of PGI2, 6-keto PGF1 alpha [29].
• Inositol phosphates produced in response to PGF2 alpha were analyzed by ion exchange column chromatography and HPLC [30].
• Pituitaries were collected 40 h after treatment with PGF 2 alpha or ovariectomy (0 h) [31].
• In situ hybridization localized mRNA for PGF2 alpha-R specifically to large luteal cells [32].
• 6. Concentration-dependent constriction to 8-epi PGF2 alpha in porcine coronary arteries was inhibited in a concentration-dependent manner by SQ29548 (10(-8) M to 10(-7) M) and BM13505 (10(-8) M to 10(-6) M) [33].

References