scholarly journals Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy

Reproduction ◽  
2004 ◽  
Vol 127 (1) ◽  
pp. 87-94 ◽  
Author(s):  
M C Henson ◽  
K F Swan ◽  
D E Edwards ◽  
G W Hoyle ◽  
J Purcell ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Late Pregnancy ◽  
Fetal Lung ◽  
Transcript Abundance ◽  
Receptor Expression ◽  
Late Gestation ◽  
Receptor Protein ◽  
Lung Maturation ◽  
Primate Model ◽  
Human Pregnancy

Leptin produced by both adipose tissue and the placental trophoblast, has been proposed to regulate numerous aspects of human conceptus development. Although recent animal studies have suggested an additional role for the polypeptide in fetal lung maturation, no evidence has been reported in primates. Therefore, we employed the baboon (Papio sp.), a well-characterized primate model for human pregnancy, to determine the presence and ontogeny of leptin receptor in fetal lung with advancing gestation. Lungs were collected from fetal baboons, early in gestation (days 58–62, n = 4), at mid gestation (days 98–102, n = 4), and late in gestation (days 158–165, n = 4) (term 184 days). mRNA transcripts for leptin (LEP) and both long and short intracellular domain isoforms of the leptin receptor (LEP-RL and LEP-RS) were assessed by RT-PCR. leptin receptor protein was evaluated by immunoblotting and cell types expressing leptin receptor were identified in late pregnancy by immunohistochemistry. Fetal serum leptin concentrations, determined by RIA, remained relatively unchanged at 5.7 ± 1.1 ng/ml (mean ± s.e.m.) in mid pregnancy and 8.4 ± 3.0 ng/ml in late pregnancy (P > 0.05). Although leptin were detectable in fetal lung, no changes in transcript abundance were apparent with advancing gestation. However, transcripts for both LEP-RL and LEP-RS receptor isoforms increased several-fold (P < 0.05) in fetal lung between mid and late gestation, while leptin receptor protein was detectable only in late pregnancy. leptin receptor was localized in distal pulmonary epithelial cells, including type II pneumocytes. In conclusion, leptin is present in the fetal baboon and its receptor is enhanced during late gestation in cells responsible for the synthesis of pulmonary surfactant. Collectively, these and past findings may suggest a modulatory role for the polypeptide in pulmonary development and/or may identify leptin receptor as a physiological marker of primate fetal lung maturity.

scholarly journals Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation

2021 ◽  
Author(s):  
Erin V. McGillick ◽  
Sandra Orgeig ◽  
Beth J. Allison ◽  
Kirsty L. Brain ◽  
Youguo Niu ◽  
...  
Keyword(s):  
Vitamin C ◽  
Lung Development ◽  
Fetal Lung ◽  
Late Gestation ◽  
Lung Maturation ◽  
Maternal Vitamin ◽  
Healthy Pregnancy ◽  
Daily Vitamin ◽  
Expression Of Genes ◽  
Fetal Lung Maturation

Abstract Background In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. Methods We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry. Results Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue. Conclusions Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy. Impact Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development. Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth. In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.

scholarly journals Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression

2004 ◽  
Vol 181 (2) ◽  
pp. 297-306 ◽  
Author(s):  
J Wilsey ◽  
PJ Scarpace
Keyword(s):  
Caloric Restriction ◽  
Leptin Receptor ◽  
Fold Increase ◽  
Receptor Expression ◽  
Male Rats ◽  
Receptor Protein ◽  
Leptin Signaling ◽  
Stat3 Phosphorylation ◽  
Long Form

The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in diet-induced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344xBN male rats, aged 6 months, were given an i.c.v. injection containing 2 micro g leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin induced a >6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptin-stimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptin-resistant DIO animals.

scholarly journals Leptin and Leptin Receptor Expression in Normal and Neoplastic Human Pituitary: Evidence of a Regulatory Role for Leptin on Pituitary Cell Proliferation1

1999 ◽  
Vol 84 (8) ◽  
pp. 2903-2911 ◽  
Author(s):  
Long Jin ◽  
Bartolome G. Burguera ◽  
Marta E. Couce ◽  
Bernd W. Scheithauer ◽  
Jesse Lamsan ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Leptin Receptor ◽  
Pituitary Cell ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Pituitary Cells ◽  
Double Labeling ◽  
Messenger Ribonucleic Acid ◽  
Anterior Pituitary Cell ◽  
Anterior Pituitary Cells

Leptin is a circulating hormone secreted by adipose and a few other tissues. The leptin receptor consists of a single transmembrane-spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms. Recent studies have suggested that the anterior pituitary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible functions of leptin in the pituitary were also analyzed. Leptin was present in 20–25% of anterior pituitary cells and was expressed in most normal anterior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was colocalized with very few PRL cells (3%), as detected by double labeling immunohistochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotroph (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries compared to adenomas. Treatment of an immortalized cultured anterior pituitary cell line, HP75, with leptin stimulated pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human HP75 and in the rat pituitary GH3 cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells. These findings show for the first time that leptin is expressed by most human anterior pituitary cell types and that there is decreased leptin protein immunoreactivity in pituitary adenomas compared to that in normal pituitary tissues. We also show that OB-Rb is widely expressed by normal and neoplastic anterior pituitary cells, implicating an autocrine/paracrine loop in the production and regulation of leptin in the pituitary.

Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus

2014 ◽  
Vol 307 (5) ◽  
pp. R538-R545 ◽  
Author(s):  
Erin V. McGillick ◽  
Janna L. Morrison ◽  
I. Caroline McMillen ◽  
Sandra Orgeig
Keyword(s):  
Mrna Expression ◽  
Fetal Lung ◽  
Glucose Transporters ◽  
Surfactant Protein ◽  
Glucose Infusion ◽  
Late Gestation ◽  
Lung Maturation ◽  
Increased Risk ◽  
Sheep Fetus ◽  
Diabetic Mothers

Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein ( SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.

scholarly journals Assessing the Association Between Fennel (Foeniculum vulgare) Extract and Serum Lipid Profile and Leptin Receptor Expression

2021 ◽  
Author(s):  
Forogh Zakernezhad ◽  
◽  
Mahmood Barati ◽  
Nima Sanadgol ◽  
Monireh Movahedi ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Profile ◽  
Serum Lipid ◽  
Leptin Receptor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Herbal Extracts ◽  
Foeniculum Vulgare ◽  
Serum Leptin ◽  
Significant Health

Introduction:Obesity is one of the most serious challenges of our era, with significant health consequences and high economic burden for health systems. Therefore, many countries have developed political agendas to cope with this ever-rising challenge. Along with chemical medications that are developed to manage obesity, researchers have focused on some natural ingredients and herbal extracts which are proved to be effective in reducing weight. The current study aimed to investigate the association between Foeniculum vulgar (fennel) extracts and body weight, lipid profile, and leptin. Methods: 35 adult male BALB/c mice were investigated, in sham, fennel 50 mg/kg, fennel 100 mg/kg, and fennel 200 mg/kg (n=7) groups. Mice were administered fennel extracts for fourteen days, while weighted at the beginning and the end of the intervention. Then, their weight, lipid profile, serum leptin, and expression of leptin protein in the hypothalamus were measured. Results: After providing the intervention, leptin receptor protein expression was increased in all groups, while serum leptin didn’t change significantly. Moreover, a significant decrease was observed in the cholesterol in the dose of 100 mg/kg/day, triglycerides in doses of 100 and 200 mg/kg/day, and LDL in doses of 50 and 100 mg/kg/day. Serum HDL was increased significantly in a dose of 100 mg/kg/day. Conclusion: Fennel extract can decrease the lipid profile by changing the expression of the leptin receptor.

Mineralocorticoid Receptor Expression in Late-Gestation Ovine Fetal Lung

2005 ◽  
Vol 12 (2) ◽  
pp. 84-91 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Charles E. Wood ◽  
Yi Hua ◽  
Daying Zhang
Keyword(s):  
Mineralocorticoid Receptor ◽  
Fetal Lung ◽  
Receptor Expression ◽  
Late Gestation ◽  
Ovine Fetal

Prepartum maturation of the lung in fetal sheep: relation to cortisol

1981 ◽  
Vol 51 (2) ◽  
pp. 384-390 ◽  
Author(s):  
J. A. Kitterman ◽  
G. C. Liggins ◽  
G. A. Campos ◽  
J. A. Clements ◽  
C. S. Forster ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Fetal Lung ◽  
Lavage Fluid ◽  
Late Gestation ◽  
Morphological Development ◽  
Lung Maturation ◽  
Physiological Factor ◽  
Fetal Sheep ◽  
Wide Range ◽  
Fetal Lung Maturation

We studied the relationship of certain fetal and maternal hormones to indicators of lung maturation in 12 fetal lambs delivered at gestational ages (GA) of 123-149 days. Maternal estrogen, maternal progesterone, and fetal prolactin did not correlate with GA or the indicators of fetal lung maturation. Fetal cortisol (range 4-165 ng X ml-1) increased with advancing GA (r = 0.747, P less than 0.01). All of the following showed a wide range of late gestation and showed a significant positive correlation with fetal cortisol: lung volumes at 40 cmH2O and 10 cmH2O on the deflation during air pressure-volume studies; saturated phosphatidylcholine (SPC) in lung tissue and in lavage fluid expressed both as mg X g-1 of wet lung and as percent of total phospholipids (%PL); total SPC (lung tissue plus lavage fluid): and SPC in lavage fluid as percent of total SPC. Lung DNA correlated inversely with GA and cortisol. All variables (except lavage fluid SPC as %PL) correlated more closely with cortisol than GA. Morphological development of lung was also related more closely to cortisol than GA. These results suggest that functional lung maturity is attained late in gestation and that endogenous cortisol is an important physiological factor in control of fetal lung maturation.

Fetal and maternal estrogen concentrations throughout pregnancy in the sheep

1981 ◽  
Vol 59 (9) ◽  
pp. 970-978 ◽  
Author(s):  
John R. G. Challis ◽  
John E. Patrick
Keyword(s):  
Early Pregnancy ◽  
Time Course ◽  
Allantoic Fluid ◽  
Late Pregnancy ◽  
Fetal Lung ◽  
Lung Maturation ◽  
Similar Time ◽  
Fetal Plasma ◽  
Estrogen Production ◽  
Pregnant Sheep

Because of the possible importance of estrogens in events of early pregnancy, and in fetal lung maturation and parturition, we have measured unconjugated estrone (E1) and estradiol (E2) concentrations in amniotic fluid (AF) and allantoic fluid (ALF) from pregnant sheep, and have compared these values with estrogen concentrations in the fetal and maternal plasma. Samples were collected under acute conditions of general anaesthesia or from chronically catheterized animals during late pregnancy. E1 always exceeded E2 in AF and ALF. On days 100 to term, the concentrations of E1 sulphate in AF and ALF greatly exceeded those of E1 but decreased towards term. E1 was elevated in AF on day 50, decreased to day 100, and in chronic preparations increased significantly before birth, at the time of the prepartum rise in E1 in maternal and fetal plasma. E1 in ALF was higher than in AF on days 50 and 100, but no consistent pattern of E1 in ALF with gestation was established, due in part to substantial interanimal variation. Similar concentrations of E2 were found in AF and ALF. In AF, E2 rose significantly before birth, with a similar time course to the prepartum rise in E2 in maternal and fetal plasma. In early pregnancy, the ratio E1/E2 in umbilical cord blood was higher than in all other compartments. We conclude (1) there is evidence for estrogen production in early pregnancy (day 50), favouring E1; (2) E1 predominates over E2 in the fetal as well as maternal compartment, although its concentration in amniotic and allantoic fluid is substantially less than E1S; (3) parturition is preceeded by rising concentrations of E1 and E2 in AF as well as in maternal and fetal plasma; and (4) this increase probably reflects rising fetoplacental production and may indicate increasing estrogen availability to the fetal membranes, uterine and fetal tissues around the time of birth.

scholarly journals Transcript abundances of the prolactin receptor, the leptin receptor and their major suppressor in the sheep mammary gland during pregnancy and lactation

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Malgorzata Szczesna ◽  
Katarzyna Kirsz ◽  
Michal Nowakowski ◽  
Dorota A. Zieba
Keyword(s):  
Mammary Gland ◽  
Leptin Receptor ◽  
Prolactin Receptor ◽  
Signal Transduction Pathway ◽  
Late Pregnancy ◽  
Transcript Level ◽  
Transcript Abundance ◽  
Cytokine Signaling ◽  
Pregnancy And Lactation ◽  
Plasma Prl

AbstractThis study aimed to expand the knowledge of the interactions between prolactin (PRL) and leptin in the ovine mammary gland during pregnancy and lactation; we examined the mRNA expression of prolactin receptor (PRLR), the long form of the leptin receptor (LRb) and suppressor of cytokine signaling (SOCS)-3 in mammary gland biopsies collected on days 60, 90 and 120 of pregnancy and on days 30, 60 and 90 of lactation (n = 6 for each time point), along with the plasma PRL and leptin concentrations. The PRL concentrations were stable throughout pregnancy and increased during lactation. The plasma leptin concentrations were comparable among nonpregnant, early-pregnant, late-pregnant and lactating ewes, but this metric peaked during mid-pregnancy. Expression of PRLR and SOCS-3 in the mammary gland fluctuated during the transition from pregnancy to lactation, and differences in LRb expression occurred during the late stages of lactation. The LRb transcript abundance was approximately 31 times higher in ewes on day 60 of lactation than in early-lactating ewes. Expression of SOCS-3 mRNA in biopsies gradually decreased over the course of pregnancy and reached a minimum value during late pregnancy. After lambing, the transcript level of SOCS-3 increased and peaked on day 60 of lactation. During pregnancy, the plasma PRL concentration positively correlated with the abundances of PRLR (r = 0.971, P < 0.01) and SOCS-3 (r = 0.818, P < 0.05). Positive correlations were also observed between the transcript abundances of SOCS-3 and LRb (r = 0.854, P < 0.05). The variations observed in the plasma PRL and leptin concentrations and the changes in expression of key leptin and PRL signal transduction pathway components, such as PRLR, LRb and SOCS-3, indicate that the efficacies of both hormone actions are modulated in a multilevel manner throughout pregnancy and lactation. These interactions may regulate the ability of the mammary gland to respond to current energy requirements and challenges, thus affecting milk yield and lactation duration.

Changes in human placental 5α-reductase isoenzyme expression with advancing gestation: effects of fetal sex and glucocorticoid exposure

2009 ◽  
Vol 21 (4) ◽  
pp. 599 ◽  
Author(s):  
Thi T. Vu ◽  
Jonathan J. Hirst ◽  
Michael Stark ◽  
Ian M. R. Wright ◽  
Hannah K. Palliser ◽  
...  
Keyword(s):  
Sex Differences ◽  
Preterm Neonate ◽  
Fetal Lung ◽  
Late Gestation ◽  
Healthy Controls ◽  
Lung Maturation ◽  
Neuroprotective Effects ◽  
Fetal Sex ◽  
Developmental Exposure ◽  
Fetal Lung Maturation

5α-Reduced steroids, including allopregnanolone, suppress neuronal activity and can have neuroprotective effects in the fetus. 5α-Reductases in the placenta may contribute precursors to brain allopregnanolone synthesis. Preterm birth and glucocorticoids, administered for fetal lung maturation or for maternal asthma, may influence reductase expression. The aims of the present study were to evaluate placental 5α-reductase isoform expression during late gestation and to examine fetal sex differences and the effects of glucocorticoid therapies on the expression of these enzymes. Expression of the two 5α-reductase isoenzymes was measured in placental samples, whereas cortisol concentrations were measured in cord blood, from two cohorts. The first cohort consisted of women who delivered preterm and received betamethasone treatment (n = 41); the second cohort consisted of women who delivered at term and were either healthy controls (n = 30) or asthmatics who had used glucocorticoids (n = 24). Placental expression of both isoenzymes increased with advancing gestation and there were marked sex differences in levels of 5α-reductase I (P < 0.05), but not of 5α-reductase II. The expression of both enzymes was positively correlated with cortisol levels (P < 0.05), but there was no effect of recent glucocorticoid exposure. These findings suggest that the preterm neonate may have lower developmental exposure to 5α-reduced steroids and may lack steroid-mediated neuroprotection depending on fetal sex.

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