scholarly journals The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

2004 ◽  
Vol 180 (2) ◽  
pp. 337-345 ◽  
Author(s):  
H Tamada ◽  
Y Shimizu ◽  
T Inaba ◽  
N Kawate ◽  
T Sawada
Keyword(s):  
Physical Properties ◽  
Aromatase Inhibitor ◽  
Mrna Expression ◽  
Lysyl Oxidase ◽  
Late Pregnancy ◽  
Estrogen Deficiency ◽  
Uterine Tissue ◽  
Pregnant Rats ◽  
Toxicological Effects ◽  
Matrix Metalloproteinase 1

It is well known that progesterone and estrogen are essential hormones for maintaining pregnancy in most mammals. Some specific roles of progesterone for the maintenance of pregnancy have been clarified, but the role of estrogen is not well known. This study examines the effects of the aromatase inhibitor, fadrozole hydrochloride (Fad), on fetuses, uterine physical properties and the mRNA expression of the uterine enzymes that are related to collagen metabolism during late pregnancy in rats. Continuous s.c. infusion with 300 micro g/day Fad from day 14 of pregnancy (day 1=the day of sperm detection) reduced the concentration of plasma estradiol-17beta (E(2)), and did not change that of plasma progesterone, compared with controls. The treatment increased the intrauterine pressure and reduced the size and compliance of the uterine tissue framework. It also caused injuries (hematomata on the extremities) in about one-quarter of fetuses by day 20. The collagen content of the uterine ampullae was not changed by the treatment. Uterine mRNA expressions of matrix metalloproteinase-1 (MMP-1), which degrades collagens, and of lysyl oxidase (LO), which is necessary for the formation of intra- and inter-molecular cross-links of collagen, were examined by quantitative RT-PCR. The treatment with Fad had no effect on the expression of MMP-1 mRNA and increased that of LO mRNA. Daily s.c. injection with 0.2 micro g E(2) restored the changes in uterine physical properties and the mRNA expression of LO caused by the Fad treatment, and prevented fetal injury, indicating that the influences of Fad treatment are due to estrogen deficiency but not to toxicological effects of Fad. These results imply that estrogen deficiency during late pregnancy in rats obstructs development of the uterine tissue framework so as to cause fetal injury. It is possible that an increase in the uterine expression of LO gene may be involved in this obstruction.

scholarly journals Streptozotocin-Induced Diabetes Decreases Mammary Gland Lipoprotein Lipase Activity and Messenger Ribonucleic Acid in Pregnant and Nonpregnant Rats

2002 ◽  
Vol 3 (1) ◽  
pp. 61-68
Author(s):  
Laura Blanco-Dolado ◽  
Antonia Martín-Hidalgo ◽  
Emilio Herrera
Keyword(s):  
Mammary Gland ◽  
Mrna Expression ◽  
Lipoprotein Lipase ◽  
Late Pregnancy ◽  
Insulin Deficiency ◽  
Pregnant Rats ◽  
Messenger Ribonucleic Acid ◽  
Mrna Content ◽  
Plasma Insulin Levels ◽  
Streptozotocin Induced Diabetes

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level.

scholarly journals Maximal expression of suppressors of cytokine signaling in the rat ovary occurs in late pregnancy

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
Keyword(s):  
Mrna Expression ◽  
Prolactin Receptor ◽  
Prostaglandin F2α ◽  
Late Pregnancy ◽  
Placental Lactogen ◽  
Cytokine Signaling ◽  
Pregnant Rats ◽  
Protein Levels ◽  
Rat Ovary ◽  
Suppressors Of Cytokine Signaling

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.

scholarly journals Reduced Hypothalamic Vasopressin Secretion Underlies Attenuated Adrenocorticotropin Stress Responses in Pregnant Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1626-1637 ◽  
Author(s):  
Shuaike Ma ◽  
Michael J. Shipston ◽  
David Morilak ◽  
John A. Russell
Keyword(s):  
Mrna Expression ◽  
Anterior Pituitary ◽  
Late Pregnancy ◽  
Secretory Response ◽  
Receptor Expression ◽  
Pituitary Cells ◽  
Pregnant Rats ◽  
V1b Receptor ◽  
Vasopressin Secretion ◽  
In Pregnancy

We sought to explain decreased ACTH secretory responses to stress in pregnant rats by investigating hypothalamic CRH and vasopressin secretion and actions on anterior pituitary corticotrophs. In late pregnancy median eminence, CRH content was reduced (by 12%). Anterior pituitary proopiomelanocortin mRNA expression, measured by in situ hybridization but not radioimmunoassayed ACTH content, was also reduced (by 45% on d 21); CRH receptor (CRHR)1 mRNA expression was unaltered in pregnancy, but V1b receptor mRNA expression was reduced (by 19%). ACTH secretory responses, measured in jugular blood, to CRH (200 ng/kg iv) or vasopressin (1.7 μg/kg, iv) were reduced on d 21 vs. virgins (49% and 44%), but the response to combined CRH and vasopressin injection was intact. Either antalarmin (CRHR1 antagonist; 20 mg/kg ip) or dP(Tyr(Me)2),Arg-NH29)AVP (V1a/b antagonist; 10 μg/kg, iv) pretreatment reduced the ACTH secretory response to forced swimming (90 sec) in virgin rats (by 57% and 40%), but only antalarmin was effective in pregnant rats (53% decrease). In vitro, measuring ACTH secretion from acutely dispersed anterior pituitary cells showed increased corticotroph sensitivity in pregnancy to CRH and to CRH augmentation by vasopressin, attributable to increased intracellular cAMP action. Hence, in late pregnancy, reduced anterior pituitary CRHR1 or V1b receptor expression did not impair corticotroph responses to CRH or vasopressin. Rather, diminished secretagogue secretion in vivo accounts for reduced action of stress levels of exogenous CRH or vasopressin alone; the late pregnancy attenuated ACTH secretory response to swim stress is deduced to be due to reduced vasopressin release by parvocellular paraventricular nuclei neurones.

scholarly journals Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention

2015 ◽  
Vol 309 (1) ◽  
pp. F63-F70 ◽  
Author(s):  
Crystal A. West ◽  
Alicia A. McDonough ◽  
Shyama M. E. Masilamani ◽  
Jill W. Verlander ◽  
Chris Baylis
Keyword(s):  
Mrna Expression ◽  
Regional Differences ◽  
Late Pregnancy ◽  
Kidney Cortex ◽  
Apical Region ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Apical Localization ◽  
In Pregnancy

Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms.

scholarly journals Identification of pluripotent cells in bovine uterus: in situ and in vitro studies

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. 317-327 ◽  
Author(s):  
Martyna Łupicka ◽  
Gabriel Bodek ◽  
Nahum Shpigel ◽  
Ehud Elnekave ◽  
Anna J Korzekwa
Keyword(s):  
Flow Cytometry ◽  
Protein Expression ◽  
Mrna Expression ◽  
Uterine Horn ◽  
Uterine Tissue ◽  
Pluripotent Cells ◽  
Flow Cytometry Assay ◽  
Myometrial Cells ◽  
Gene And Protein Expression

The aim of this study was to identify uterine pluripotent cells both in bovine uterine tissues as well in epithelial, stromal, and myometrial uterine cell populations. Moreover, the relationship of pluripotent markers expression with age and the uterine horn side was considered. Uterine tissue was collected from ipsilateral and contralateral horns (days 8–10 of the estrous cycle). Immunohistostaining for C-KIT, OCT3/4, NANOG, and SOX2 in uterine tissue was determined. mRNA expression of C-KIT, OCT3/4, NANOG and SOX2 was evaluated in uterine tissue relative to the age of the cow and uterine horn side. Gene and protein expression of these markers in the uterine luminal epithelial, stromal, and myometrial cells was evaluated by real-time PCR and western blotting respectively. The expression of pluripotent cell markers OCT3/4, NANOG, and SOX2 was identified by flow cytometry assay in epithelial, stromal, and myometrial cells. Multilineage differentiation of the bovine uterine cells was performed. mRNA expression of OCT3/4, NANOG, and SOX2 in uterine tissue was higher in the ipsilateral horn than in the contralateral horn. Flow cytometry assay revealed positive fluorescence for OCT3/4, NANOG, and SOX2 in all uterine cell types. Results showed the age-dependent expression of pluripotent markers in uterine tissue. Beside, the different expression of pluripotent cells in each horn of uterus suggests the influence of ovarian hormones on these characteristics. The highest mRNA and protein expression for pluripotent markers was observed in stromal cells among uterine cells, which indicates this population of cells as the main site of pluripotent cells in the cow uterus.

scholarly journals Englitazone administration to late pregnant rats produces delayed body growth and insulin resistance in their fetuses and neonates

2005 ◽  
Vol 389 (3) ◽  
pp. 913-918 ◽  
Author(s):  
Julio Sevillano ◽  
Inmaculada C. López-Pérez ◽  
Emilio Herrera ◽  
María del Pilar Ramos ◽  
Carlos Bocos
Keyword(s):  
Body Mass ◽  
Control Cell ◽  
Late Pregnancy ◽  
Tissue Growth ◽  
Peroxisome Proliferator ◽  
Pregnant Rats ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akt Phosphorylation ◽  
Insulin Resistant

The level of maternal circulating triacylglycerols during late pregnancy has been correlated with the mass of newborns. PPARγ (peroxisome-proliferator-activated receptor γ) ligands, such as TZDs (thiazolidinediones), have been shown to reduce triacylglycerolaemia and have also been implicated in the inhibition of tissue growth and the promotion of cell differentiation. Therefore TZDs might control cell proliferation during late fetal development and, by extension, body mass of pups. To investigate the response to EZ (englitazone), a TZD, on perinatal development, 0 or 50 mg of englitazone/kg of body mass was given as an oral dose to pregnant rats daily from day 16 of gestation until either day 20 for the study of their fetuses, or until day 21 of gestation for the study of neonates. EZ decreased maternal triacylglycerol levels at day 20 of gestation and neonatal mass, but not fetal mass. Fetuses and neonates from EZ-treated mothers exhibited high levels of insulin and were found to be hyperglycaemic. The apparent insulin-resistant state in neonates from EZ-treated pregnant rats was corroborated, since they showed higher plasma NEFA [non-esterified (‘free’) fatty acid] levels, ketonaemia and liver LPL (lipoprotein lipase) activity and lower plasma IGF-I (type 1 insulin-like growth factor) levels, in comparison with those from control mothers. Moreover, at the molecular level, an increase in Akt phosphorylation was found in the liver of neonates from EZ-treated mothers, which confirms that the insulin pathway was negatively affected. Thus the response of fetuses and neonates to maternal antidiabetic drug treatment is the opposite of what would be expected, and can be justified by the scarce amount of adipose tissue impeding a normal response to PPARγ ligands and by hyperinsulinaemia as being responsible for a major insulin-resistant condition.

METABOLISM OF 20β-HYDROXY-4-PREGNEN-3-ONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

1976 ◽  
Vol 83 (3) ◽  
pp. 604-620 ◽  
Author(s):  
B. P. Lisboa ◽  
M. Holtermann
Keyword(s):  
Biological Activity ◽  
Adult Female ◽  
Female Rats ◽  
Uterine Tissue ◽  
Rat Uterus ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Progesterone Metabolites ◽  
Ovariectomized Adult Rats

ABSTRACT In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20β-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20β-hydroxy-4-pregnen-3-one to progesterone. Since a hepatic 20β-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20β-hydroxy-4-pregnen-3-one in these animals. Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20β-hydroxy-4-pregnen-3-one with uterine tissue: 20β-hydroxy-5α-pregnan-3-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3α,20β-diol, 4-pregnene-3α,20β-diol and 4-pregnene-3β,20β-diol. The conversion of 20β-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus. 20β-hydroxy-5β-pregnan-3-one is the first C21-metabolite with a 5β(H)-configuration isolated in the rat uterus, which indicates the presence of 5β-reductase in this tissue.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

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.

Thyroid and parathyroid-independent increase in plasma 1,25-dihydroxyvitamin D during late pregnancy in the rat

1988 ◽  
Vol 116 (3) ◽  
pp. 381-385 ◽  
Author(s):  
T. M. Nguyen ◽  
A. Halhali ◽  
H. Guillozo ◽  
M. Garabedian ◽  
S. Balsan
Keyword(s):  
Vitamin D ◽  
Placental Transfer ◽  
Plasma Concentrations ◽  
Late Pregnancy ◽  
Maternal Plasma ◽  
Vitamin D Metabolites ◽  
Pregnant Rats ◽  
Dihydroxyvitamin D ◽  
Fetal Plasma ◽  
And Control

ABSTRACT The effect of thyroparathyroidectomy (TPTX) on the plasma concentrations of the vitamin D metabolites (25-(OH)D, 24,25-(OH)2D and 1,25-(OH)2D) has been studied in pregnant rats and their fetuses during the last quarter of gestation. Maternal and fetal vitamin D metabolites were not significantly affected by TPTX. A significant increase in plasma 1,25-(OH)2D concentrations was observed in both TPTX and control mothers and fetuses from days 19 to 21. Fetal and maternal plasma 25-(OH)D were positively correlated in both control and TPTX groups. Such a correlation was also found for 24,25-(OH)2D in the two groups. In contrast, a positive correlation between maternal and fetal plasma concentrations of 1,25-(OH)2D was found in TPTX but not in control rats. These data suggest that major alterations in calcium metabolism, such as that produced by maternal TPTX, are insufficient to affect the changes in maternal and fetal plasma 1,25-(OH)2D during late pregnancy significantly. They also suggest that parathyroid hormone, thyroxine, and/or calcitonin may control a possible placental transfer of 1,25-(OH)2D in the rat. J. Endocr. (1988) 116, 381–385

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