Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1261-G1273 ◽  
Author(s):  
Aldo D. Mottino ◽  
Tim Hoffman ◽  
Lothar Jennes ◽  
Jingsong Cao ◽  
Mary Vore

We analyzed the expression of multidrug resistance-associated protein 2 (mrp2) in the small intestine of control female rats and in rats during late pregnancy (19–20 days of pregnancy) and lactation (2–4, 10–14, and 21 days after delivery). Western blot analysis was performed on brush-border membranes prepared from different regions of the small intestine. Expression of mrp2 was maximal in the proximal segments for all experimental groups, was preserved in pregnant rats, and increased by 100% in postpartum rats by late lactation with respect to control animals. Northern blot analysis of mrp2 mRNA revealed a positive correlation with protein levels. Transport of S-glutathione-dinitrophenol (DNP-SG) from the intestinal cell to the lumen was analyzed in the everted intestinal sac model. Secretion of DNP-SG was not altered in pregnant rats but increased in lactating animals by late lactation. Intestinal mrp2 mRNA, protein, and transport activity are increased in lactating rats, suggesting that this may represent an adaptive mechanism to minimize the toxicity of dietary xenobiotics in response to increased postpartum food consumption.

2020 ◽  
Vol 11 (5) ◽  
pp. 533-539 ◽  
Author(s):  
Diana C. Castro-Rodríguez ◽  
Gimena Juárez-Pilares ◽  
Luz Cano-Cano ◽  
Mariana Pérez-Sánchez ◽  
Carlos A. Ibáñez ◽  
...  

AbstractMaternal obesity (MO) during pregnancy and lactation leads to maternal and offspring metabolic dysfunction. Recent research has suggested that probiotics might be a novel approach to counteract these unwanted MO effects. The aim of this research was to analyze the impact of Leuconostoc SD23, a probiotic isolated from aguamiel (traditional Mexican drink), on MO metabolism in rats at the end of lactation (21 days). From weaning through lactation, control female Wistar rats (C) ate chow (5% fat) or high-energy obesogenic diet (MO; 25% fat). Half the C and MO mothers received a daily dose (1 × 1010 CFU/ml) of probiotic orally, control with probiotic (CP) and MO with probiotic (MOP), 1 month before mating and through pregnancy and lactation. Histological analyses of the liver, white adipose tissue and small intestine, body composition, glucose, insulin, triglycerides, and leptin were determined in mothers at the end of lactation. Maternal weight during pregnancy was greater in MO than C mothers, but similar at the end of lactation. Probiotic intervention had no effect on maternal weight. However, at the end of lactation, percentage of body fat was higher in MO than C, CP, and MOP. Serum glucose, homeostasis model assessment of insulin resistance, and triglycerides were higher in MO versus C, CP, and MOP. MO small intestine villus height was higher versus MOP, C, and CP. Leuconostoc SD23 did not present adverse effects in C. Conclusions: maternal administration of Leuconostoc SD23 has beneficial effects on maternal metabolism, which holds possibilities for preventing adverse offspring metabolic programming.


2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.


2020 ◽  
Vol 245 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Hui Yu ◽  
Zoe Thompson ◽  
Sylee Kiran ◽  
Graham L Jones ◽  
Lakshmi Mundada ◽  
...  

Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) are essential for normal energy homeostasis. Maximal ARC Pomc transcription is dependent on neuronal Pomc enhancer 1 (nPE1), located 12 kb upstream from the promoter. Selective deletion of nPE1 in mice decreases ARC Pomc expression by 70%, sufficient to induce mild obesity. Because nPE1 is located exclusively in the genomes of placental mammals, we questioned whether its hypomorphic mutation would also alter placental Pomc expression and the metabolic adaptations associated with pregnancy and lactation. We assessed placental development, pup growth, circulating leptin and expression of Pomc, Agrp and alternatively spliced leptin receptor (LepR) isoforms in the ARC and placenta of Pomc∆1/∆1 and Pomc+/+ dams. Despite indistinguishable body weights, lean mass, food intake, placental histology and Pomc expression and overall pregnancy outcomes between the genotypes, Pomc ∆1/∆1 females had increased pre-pregnancy fat mass that paradoxically decreased to control levels by parturition. However, Pomc∆1/∆1 dams had exaggerated increases in circulating leptin, up to twice of that of the typically elevated levels in Pomc+/+ mice at the end of pregnancy, despite their equivalent fat mass. Pomc∆1/∆1dams also had increased placental expression of soluble leptin receptor (LepRe), although the protein levels of LEPRE in circulation were the same as Pomc+/+ controls. Together, these data suggest that the hypomorphic Pomc∆1/∆1 allele is responsible for the perinatal super hyperleptinemia of Pomc∆1/∆1 dams, possibly due to upregulated leptin secretion from individual adipocytes.


2002 ◽  
Vol 7 (2) ◽  
Author(s):  
M. A. SILVA ◽  
L. E. KOZICKI ◽  
P. R. DALSENTER

Na presente pesquisa objetivou-se estudar os efeitos do gossipol (C30H30O8) na gestação e consequente lactação, de 40 ratas com idade média de 120 dias e peso variando entre 200 e 250 gramas, oriundas do Biotério Central da Universidade Federal do Paraná. Os animais foram acompanhados diariamente até a confirmação da cobertura através de esfregaço de lavado vaginal (esfregaço positivo - presença de espermatozóides) e separados em quatro grupos de dez animais: G I - controle, G II – gossipol 20 mg.kg-1, G III – gossipol 40 mg.kg-1, G IV - gossipol 80 mg.kg-1 respectivamente de acordo com a concentração de gossipol presente na suspensão utilizada (gossipol 20 mg.mL-1, gossipol 40 mg.mL-1 e gossipol 80 mg.mL-1). O gossipol ácido acético (GAA 97,8 % de pureza) diluído em óleo vegetal de canola (veículo) foi administrado oralmente para todos os animais no volume de 1 mL de suspensão para cada quilo de peso vivo. A administração da droga iniciou-se no 5o dia de gestação estendendo-se até o 20º. O peso das ratas foi aferido diariamente, do dia da cobertura até o dia do parto, a fim de se observar possíveis efeitos tóxicos durante a gestação. Durante a lactação as ratas e os filhotes eram pesados a cada 3 dias para acompanhar o desenvolvimento dos filhotes e recuperação materna. No desmame (21o dia pós-parto) todas as fêmeas foram sacrificadas para a observação dos pontos uterinos de implantação, comparando-se o número de fetos nascidos com o número de fetos gerados. Durante o experimento sete ratas do grupo G IV e uma do G III morreram, além de abortos e sinais de canibalismo na parturição. Observou-se como sinais de toxicidade: diarréia, inapetência, pelos eriçados, taquipnéa e perda de peso. Nenhum filhote apresentou alterações morfológicas macroscópicas. Concluiu-se que o gossipol (GAA) causou intoxicação grave nos animais que receberam maior dosagem, bem como interferiu no ganho de peso das ratas durante a gestação, peso ao nascimento e peso à desmama dos filhotes. Contudo não interferiu no processo de manutenção da gestação e no número de filhotes nascidos quando administrado entre o 5o e 20º dia de gestação. Gossypol toxicity in pregnant and nursing rats – Rattus rattus norvegicus Abstract In order to study the effects of gossypol (C30H30O8) in pregnancy and lactation, 40 female rats (120 days old) weighing between 200 and 250 grams, were used in this experiment. The animals were divided in four different group GI (n = 10), GII (n = 10), GIII (n = 10) and GIV (n = 10). The daily oral dose administered by gavage to the animals of each group was of 0, 20, 40 and 80 mg.kg-1 respectively of gossypol dissolved in canole oil. All rats were weighed daily from the day of copulation (0 day) to the day of parturition, for evaluation of the toxic effects during pregnancy. All rats and their offspring were weighed on days 3, 6, 9, 12, 15, 18 and 21 (day of weaning) of lactation. At the day of weaning, all rats were killed in order to observe the number of uterine implantation sites. Eight rats (1 from GIII group and 7 from GIV) died during the period of drug administration besides the occurrence of abortions and cannibalism at the parturition. Clinical symptoms of toxicity were diarrhea, inappetency, bristly hair, tachypnea, loss of weight. Neither pup displayed either macroscopic or morphological alterations. Heavy poisoning has been induced in rats that received higher doses of gossypol acetate as well as a dose-dependent decrease in body weight gain in pregnant rats, lesser weight at birth and at weaning. Nevertheless, gossypol did not interfere in the maintenance of pregnancy and in the number of pups born when administered from day 5 through day 20 of pregnancy.


1990 ◽  
Vol 124 (2) ◽  
pp. 191-198 ◽  
Author(s):  
L. Carlsson ◽  
S. Edén ◽  
J.-O. Jansson

ABSTRACT The plasma GH levels of female rats during late pregnancy were determined using an automatic method for repetitive blood sampling from conscious animals. The plasma GH patterns were analysed by a pulse analysis computer program (PULSAR). The mean plasma GH levels were about twofold higher in pregnant females on days 15, 18 and 22 of gestation than in age-matched non-pregnant females. The basal plasma GH levels were also increased, while there was no change in GH pulse amplitude or frequency. The augmentation of GH release was even more pronounced on day 20 of gestation, with a fourfold increase in mean plasma GH levels compared with those in non-pregnant females. This increase reflected an increase in both basal plasma GH levels and GH pulse amplitude, but there was no increase in pulse frequency. In female rats that delivered on day 22 of gestation, the basal and mean plasma GH levels increased during parturition. Pregnant females consistently responded to multiple i.v. infusions of 1 μg human GH-releasing factor analogue (hGRF(1–29)-NH2) given at 45-min intervals on day 18 of gestation. Both basal and GRF analogue-stimulated plasma GH levels were undetectable after hypophysectomy of pregnant rats. The present study demonstrates an increase in basal plasma GH levels during late pregnancy and a marked increase in both basal plasma GH levels and GH pulse amplitude on day 20 of gestation. Furthermore, hypophysectomy of pregnant rats results in undetectable GH levels, indicating that the high levels of GH during pregnancy are derived from the pituitary. Journal of Endocrinology (1990) 124, 191–198


Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 537-544 ◽  
Author(s):  
Stephen T Anderson ◽  
Naajia N M Isa ◽  
Johanna L Barclay ◽  
Michael J Waters ◽  
Jon D Curlewis

Maintenance of the rodent corpus luteum (CL) during pregnancy requires prolactin receptor (PRLR) signal transduction via STAT5. At the end of pregnancy, prostaglandin F2α (PGF2α) induces luteal regression through many mechanisms, including downregulation of PRLR signaling. We have previously shown that a PGF2α analog upregulates suppressors of cytokine signaling (SOCS) proteins in the CL of day 19 pregnant rats leading to reduced STAT5 signaling. Here, we examined endogenous SOCS expression and STAT5 signaling in the rat ovary during normal pregnancy and luteolysis. The mRNA expression of Socs1, Socs2, and Socs3 and related cytokine-inducible SH2-containing protein (Cish) was low in early pregnancy (day 7), but significantly increased at mid-pregnancy (days 10 and 13) associated with increased endogenous tyrosine phosphorylation (TyrP) of STAT5. In support of the notion that these changes are due to increasing placental lactogen levels at this time, we found that treatment with exogenous PRL on day 7 increased TyrP of STAT5 and induced SOCS mRNA expression, except Socs3. After mid-pregnancy, further significant increases in Socs3 and Cish mRNA expression were observed. Such changes in mRNA expression correlated with protein levels, with protein levels of both SOCS3 and CISH being maximal in late pregnancy (days 19–21). In addition, a significant reduction in TyrP of STAT5 was first observed on day 20, with a further substantial decrease on day 21. Therefore, these results are consistent with the hypothesis that increased SOCS expression in the rat ovary during late pregnancy reduces STAT5 signaling, which may be important in PGF2α-induced luteolysis.


1987 ◽  
Vol 242 (1) ◽  
pp. 75-80 ◽  
Author(s):  
M S Ardawi

The maximal activity of phosphate-dependent glutaminase was increased in the small intestine, decreased in the liver and unchanged in the kidney of late-pregnant rats. This was accompanied by increases in the size of both the small intestine and the liver. The maximal activity of phosphate-dependent glutaminase was increased in both the small intestine and liver but unchanged in the kidney of peak-lactating rats. Enterocytes isolated from late-pregnant or peak-lactating rats exhibited an enhanced rate of utilization of glutamine and production of glutamate, alanine and ammonia. Arteriovenous-difference measurements across the gut showed an increase in the net glutamine removed from the circulation in late-pregnant and peak-lactating rats, which was accompanied by enhanced rates of release of glutamate, alanine and ammonia. Arteriovenous-difference measurements for glutamine showed that both renal uptake and skeletal-muscle release of glutamine were not markedly changed during late pregnancy or peak lactation; but pregnant rats showed a hepatic release of the amino acid. It is concluded that, during late pregnancy and peak lactation, the adaptive changes in glutamine metabolism by the small intestine, kidneys and skeletal muscle of hindlimb are similar; however, the liver appears to release glutamine during late pregnancy, but to utilize glutamine during peak lactation.


1980 ◽  
Vol 84 (3) ◽  
pp. 363-370 ◽  
Author(s):  
J. F. WILSON ◽  
MERRILL A. MORGAN

α-Melanotrophin was detected by radioimmunoassay in the pituitary glands of fetal rats from day 17 of gestation. The pituitary content of α-melanotrophin increased regularly, at a gradually decreasing rate, throughout gestation and in the postnatal period. Concentrations of α-melanotrophin in the plasma of fetal and newborn rats were below the detection limit of the radioimmunoassay (10 pmol/l). Detectable concentrations were first found in young rats on day 3 after birth and did not differ significantly from those in their mothers throughout the period of suckling. Plasma concentrations of α-melanotrophin were raised in pregnant rats during the last 4 days of gestation and after parturition. They returned to basal levels in the 2 weeks after delivery. After weaning at 3 weeks of age, a large increase in the plasma concentration of α-melanotrophin was detected in juvenile rats. Plasma levels had returned to the normal adult range by 6 weeks of age. The increases in α-melanotrophin in the blood were thought to be the result of non-specific stress effects. The data did not provide evidence for a role for α-melanotrophin in reproductive processes in the rat.


2008 ◽  
Vol 200 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Anshu Gupta ◽  
Malathi Srinivasan ◽  
Supaporn Thamadilok ◽  
Mulchand S Patel

The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats; additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation compared with control female rats that were fed a standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups. FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor β-subunit. However, the protein levels of signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agouti-related polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides and leptin and insulin signaling in the late fetal period.


1980 ◽  
Vol 238 (1) ◽  
pp. E26-E31 ◽  
Author(s):  
P. B. Mutch ◽  
L. S. Hurley

The effect of dietary zinc deficiency during late pregnancy and lactation on the rat mammary gland was investigated by feeding female rats either a zinc-deficient diet (0.4 ppm Zn) or a zinc-sufficient diet (100 ppm Zn) ad libitum or restricted in amount. Zinc deficiency from day 0 of lactation specifically reduced the total RNA content of lactating mammary glands on day 14, but had no effect beyond that of food restriction on their total DNA content, Both RNA and DNA content of the mammary gland were decreased by reduced food intake. Zinc deficiency from day 14 of pregnancy to day 2 of lactation severely impaired parturition and prevented the normal rise in mammary gland RNA seen during lactogenesis in control animals. A shorter deficiency period, from day 18 of gestation, had no effect on mammary gland nucleic acids other than that due to inanition.


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