Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were undertaken to identify intracellular mediators of prolactin inhibition of glucocorticoid-induced apoptosis in Nb2 lymphoma cells. A short-term assay was implemented that quantitates fragmented DNA released from the genome by reaction with diphenylamine. Induction and inhibition of internucleosomal DNA cleavage (indicative of apoptosis) was verified by agarose gel electrophoresis of extracted cellular DNA. Synchronized Nb2 cells (G0/G1) exhibited increased DNA fragmentation after 4-hr incubation with dexamethasone (DEX) (25-100 nM) which was inhibited by ovine prolactin (oPRL) (0.1-1 ng/ml), the glucocorticoid receptor antagonist, RU486 (500 nM), and the nuclease inhibitor, aurintricarboxylic acid (100 microM). Signals previously implicated in prolactin induction of mitogenesis in Nb2 cells were investigated for their role in prolactin inhibition of apoptosis including: protein kinase C activation, arachidonic acid metabolism, polyamine production, tyrosine phosphorylation, and extracellular calcium. Protein kinase C agonists, phorbol-12-myristate-13-acetate, and 1,2-dioctanoyl-sn-glycerol, +/- the calcium ionophore, A23187 (200 nM), did not mimic oPRL inhibition of DEX-induced DNA fragmentation. Protein kinase C inhibitors, gossypol and quercetin, did not block prolactin action. Arachidonic acid did not mimic prolactin protection against DEX-induced DNA fragmentation. Inhibitors of arachidonic acid metabolism, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and indomethacin did not block prolactin action. The polyamine, spermine, inhibited DEX-induced DNA fragmentation at 1.5 to 2.5 mM. However, inhibition of polyamine synthesis with alpha-difluoromethyl ornithine or methylglyoxal bis(guanylhydrazone) did not inhibit prolactin action. Prolactin action was not blocked by inhibitors of tyrosine kinase activation, genistein and tyrphostin-47. On the other hand, pervanadate, a potent tyrosine phosphatase inhibitor, consistently inhibited DEX-induced DNA fragmentation. Prolactin action and DEX-induced apoptosis both occurred in calcium-free PBS. In summary, protein kinase C activation and eicosanoid production do not appear to mediate this prolactin action. Although spermine could block DNA fragmentation, blockade of the polyamine cascade did not inhibit prolactin action, suggesting that polyamines do not mediate this prolactin effect. While inhibitors of tyrosine kinase activation did not block prolactin action, tyrosine phosphatase inhibition in the presence of basal tyrosine kinase activity mimicked prolactin action, suggesting tyrosine phosphorylation participation in the anti-apoptotic effect. Extra-cellular calcium was not required for prolactin or DEX action.
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PMID:Investigation of intracellular signals mediating the anti-apoptotic action of prolactin in Nb2 lymphoma cells. 777 88

Prostaglandins primarily of uterine origin play an important role in parturition. Hysterectomy of nongravid pigs early in the luteal phase maintains luteal function until about Day 150, whereas the duration of normal pregnancy is about 114 days. A precisely timed peak release of relaxin and coincident decrease in progesterone secretion in unmated hysterectomized gilts are similar to hormonal changes that occur a few hours before parturition. It is hypothesized that prostaglandin F2alpha (PGF2alpha) in hysterectomized pigs mimics abrupt changes in ovarian and pituitary hormone secretion seen before normal parturition and in early lactation. Unmated Yorkshire gilts were hysterectomized on Days 6-8 of a normal estrous cycle, and at 1200 h on Day 113, they were given an i.m. injection of 30 mg PGF2alpha-trihydroxymethylaminomethane (THAM) salt or PBS. None of these gilts expressed behavioral estrus immediately after PGF2alpha or vehicle treatment. On Day 113, PGF2alpha increased peak relaxin (60 ng/ml) compared with that of controls (34 ng/ml; p < 0.01), whereas progesterone decreased abruptly (4 vs. 16 ng/ml in PGF2alpha and PBS; p < 0.01). Prolactin remained at < 5 ng/ml from Day 98 to 120 in controls but peaked at 33 ng/ml immediately after PGF2alpha treatment on Day 113, and then decreased to levels similar to those of controls on Day 120. Sequential bleeding revealed an acute growth hormone release (4.5 ng/ml) immediately after PGF2alpha injection and return to basal levels (< 0.6 ng/ml) on Days 114-120. PGF2alpha induced abrupt shifts in progesterone, relaxin, prolactin, and growth hormone secretion in hysterectomized gilts that mimicked hormone changes seen in late pregnancy, parturition, and early lactation. These findings provide new insight into the role of PGF2alpha in abruptly changing hormone secretions by aging corpora lutea and the pituitary gland even in the absence of conceptuses or the uterus in the pig.
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PMID:Prostaglandin F2alpha-induced luteolysis of aging corpora lutea in hysterectomized pigs. 954 36

Antibody against porcine relaxin (antipRLX540; 1:950,000) was produced in sheep and used to determine the effect on relaxin and progesterone secretion, and on parturition in late pregnant pigs. In group 1, Yorkshire gilts with normal estrous cycles were bred on the second observed estrus and fitted with an indwelling jugular cannula and an intraperitoneal cannula on day 100 of pregnancy. Gilts were infused at 6-h intervals with antipRLX540 (n = 10) or PBS (n = 10) beginning on day 103 until parturition. From days 103 to 120, daily blood samples (10 ml) were collected for RIA of relaxin, progesterone, and prolactin. In group 2, bred gilts were randomly assigned to antipRLX540 (n = 11), relaxin (n = 5), and PBS (n = 8) treatment on days 111, 113, and 115. Blood was collected twice daily from day 108 to 120, and every 20 min on days 111, 113, and 115 beginning 60 min before treatment and continuing 180 min. Parturition in gilts given antipRLX540 occurred on day 112.7 compared with day 114.0 in relaxin-treated gilts and day 114.3 in PBS controls (P < 0.05). Duration of delivery from first to last piglet was greatly delayed in antipRLX540 gilts (240 min) compared with PBS controls ([117 min] P < 0.005). Average number of stillborns was greater in antipRLX540- than in PBS-treated controls (2.4 vs. 1.0; P < 0.05). Relaxin concentration in peripheral plasma was lower in antipRLX540-treated gilts from day 105 to 110, but on day 113 the antipRLX540-treated group had a greater relaxin peak release compared with PBS-treated animals (P < 0.05). Plasma progesterone concentrations were similar in antipRLX540- and PBS-treated gilts throughout the period of the study. In group 2, by day 113, progesterone decreased in antipRLX540-treated gilts compared with relaxin- and PBS-treated gilts. Prolactin levels were similar in both antipRLX540- and PBS-treated gilts; however, from 1 to 3 days postpartum the antipRLX540 group had higher prolactin concentration (P < 0.05). The results indicate that antipRLX540 decreased circulating plasma concentrations of unbound or free relaxin during the last 10 days of pregnancy in Yorkshire gilts. AntipRLX540 markedly increased both the duration of delivery of piglets and the average number of stillbirths in this litter-bearing species compared with PBS-treated controls. This study provides strong evidence that increasing circulating concentrations of relaxin during late pregnancy is crucial for unimpaired parturition in the pig.
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PMID:Antiporcine relaxin (antipRLX540) treatment decreases relaxin plasma concentration and disrupts delivery in late pregnant pigs. 982 4