Effects of the Antiglucocorticoid RU 486 on the Maturation of Fetal Rat Lung Surfactant

Guettari, N.; Marin, L.; Bourbon, Jacques R.; Dufour, Marie Noëlle; Rieutort, Michel; Tordet, C.

doi:10.3109/01902148909087850

Cited by 10 publications

(6 citation statements)

References 33 publications

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“…In a previous study [3], we have shown that RU 486 treatment of pregnant rats, starting on day 16 of gestation, resulted in a slowing down of surfactant phospholipid ac cumulation in fetal lungs. However, type-II pneumocytes appeared on day 19, as in the course of normal development.…”

Section: Discussionmentioning

confidence: 99%

“…The RU 486 treatment of pregnant rats from day 16 of gestation enabled us to dem onstrate unequivocally that endogenous glu cocorticosteroids (GCSs) are involved in the control of fetal lung maturation by specifi cally enhancing surfactant phospholipid bio synthesis at late stages of intrauterine devel opment [3]. However, this treatment did not prevent the appearance of type-II cells [3], responsible for surfactant biosynthesis [4], Moreover, these were first found on day 19 of gestation, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…However, this treatment did not prevent the appearance of type-II cells [3], responsible for surfactant biosynthesis [4], Moreover, these were first found on day 19 of gestation, i.e. at a normal stage [5],…”

Section: Introductionmentioning

confidence: 99%

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Effects of the Antiglucocorticoid RU 486 on the Initiation of Ultrastructural Type-II Cell Differentiation in Fetal Rat Lung

Guettari¹,

Dufour²,

Marin³

1990

Neonatology

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The possible early role of endogenous glucocorticosteroids on the further ultrastructural development of the fetal rat lung epithelium was investigated in vitro using a potent antiglucocorticoid drug, RU 486. Lung primordia were explanted on day 13 of gestation and cultured for 4–6 days in the presence of fetal calf serum, with or without RU 486 in excess. The results obtained show that osmiophilic lamellar bodies specific for morphologically differentiated type-II cells did appear in a number of epithelial cells, even though the glucocorticosteroids possibly present in the culture medium, or transferred at explantation were antagonized by RU 486. The number of lamellar bodies stored in these pneumocytes was not different from that in controls. In contrast, their total surface area per cell profile was transiently decreased. Taken together the reported data strongly suggest that endogenous glucocorticosteroids are not necessary for the initiation of type-II cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of the Antiglucocorticoid RU 486 on the Initiation of Ultrastructural Type-II Cell Differentiation in Fetal Rat Lung

Guettari¹,

Dufour²,

Marin³

1990

Neonatology

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“…Glucocorticoids increase phospholipid production [27] and transcription of SP-B and SP-C [28] during ontogeny. Their effects on SP-A transcription during fetal develop ment are much more complex [29], In cul tured type II cell carcinoma lines, glucocorti coids increase transcription of SP-B [30].…”

Section: Discussionmentioning

confidence: 99%

Applications of Anti-Curosurf Antibodies to Understanding the Biology of Alveolar Surfactant

Strayer¹

1992

Neonatology

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The structure of surfactant-binding proteins from alveolar cell membranes was investigated using monoclonal anti-idiotypic antibodies directed against surfactant-binding regions of anti-surfactant monoclonal antibodies. Two different series of monoclonal anti-surfactant antibodies were used. One series included antibodies against rabbit surfactant, and the other antibodies against porcine surfactant. In addition, two monoclonal anti-idiotype antibodies were made. These anti-idiotype antibodies, called A2R and A2C, bind both anti-Curosurf and anti-rabbit surfactant antibodies comparably. They recognize a 30-kDa cell membrane protein on alveolar and bronchial epithelial cells. In addition, A2C and A2R block the binding of radiolabeled surfactant to these cells. Using a combination of A2C and A2R cDNA expression libraries from both human and porcine lungs were screened. One independent clone was identified in each library that produced protein that bound these monoclonal antibodies. The protein encoded by the cDNA in each clone bound radiolabeled recombinant surfactant protein-A. It is concluded that human and porcine alveolar cell SP-A binding proteins have been identified and its cDNA cloned. The potential implications of this finding for the understanding and treatment of surfactant deficiency states are considerable.

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“…In the context of substantial increases in circulating glucocorticoid concentrations during late gestation, these findings may be of physiologic importance to the biochemical maturation of the antenatal lung. (Pediatr Res 38: 506-512, 1995) Abbreviations GR, glucocorticoid receptor FBS, fetal bovine serum FPF, fibroblast-pneumocyte factor MEM, minimal essential medium SP-A, surfactant protein-A Glucocorticoids accelerate the onset of mature levels of surfactant synthesis by fetal mammalian lung (1-3) via the classic GR mechanism (1, 2, [4][5][6][7][8][9]. However, in many tissues, glucocorticoids decrease GR expression, thereby decreasing tissue responsiveness to glucocorticoid stimulation.…”

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Differential Regulation of Glucocorticoid Receptor Expression by Ligand in Fetal Rat Lung Cells

et al. 1995

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The glucocorticoid receptor (GR) mediates glucocorticoid stimulation of surfactant production by fetal mammalian lung. In many other tissues, glucocorticoids decrease expression of GR, thereby reducing responsiveness to these hormones. We therefore determined whether there is a similar effect of exogenous glucocorticoids on GR in fetal rat whole lung, and in the principal cell types involved in the stimulation of surfactant, the fibroblasts and the epithelial cells. The ontogeny of GR in late gestation lung differed between the two cell types, with maximal levels occurring in fibroblasts on gestational d 19, and on d 20 in epithelial cells. Administration of dexamethasone (1 mg/kg) to the mother on gestational d 18 or 19 (term = 22 d) increased specific GR binding activity in whole lung 24 h later. Furthermore, in vitro, incubation of cultured fibroblasts of gestational d 20 with 10K7 M cortisol increased GR immunoreactive protein and binding activity in a dose-and time-dependent manner, without affecting cellular levels of GR mRNA. However, identical treatment of d 20 distal airway epithelial cells was followed by decreased GR protein without significant change in cellular GR mRNA. Surfactant protein-A protein levels, taken as assessments of lung maturation, were increased in response to the same treatment. Our findings suggest that hormonal regulation of GR in fetal lung cells occurs at a posttranscriptional level, and is cell-specific. In the context of substantial increases in circulating glucocorticoid concentrations during late gestation, these findings may be of physiologic importance to the biochemical maturation of the antenatal lung. (Pediatr Res 38: [506][507][508][509][510][511][512] 1995) Abbreviations GR, glucocorticoid receptor FBS, fetal bovine serum FPF, fibroblast-pneumocyte factor MEM, minimal essential medium SP-A, surfactant protein-A Glucocorticoids accelerate the onset of mature levels of surfactant synthesis by fetal mammalian lung (1-3) via the classic GR mechanism (1, 2, 4-9). However, in many tissues, glucocorticoids decrease GR expression, thereby decreasing tissue responsiveness to glucocorticoid stimulation. The effect of glucocorticoids on GR in late gestation fetal lung around the time of the onset of augmented surfactant production is incompletely understood.Administration of glucocorticoids decreases GR mRNA (10) and GR protein (1 1) in several adult rat organs, including lung. In various cell lines, glucocorticoids lower GR number by decreasing GR transcription rates without altering affinity for ligand (12,13). However, it is recognized that the response of GR mRNA steady-state levels to glucocorticoid treatment can

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Effects of the Antiglucocorticoid RU 486 on the Maturation of Fetal Rat Lung Surfactant

Cited by 10 publications

References 33 publications

Effects of the Antiglucocorticoid RU 486 on the Initiation of Ultrastructural Type-II Cell Differentiation in Fetal Rat Lung

Effects of the Antiglucocorticoid RU 486 on the Initiation of Ultrastructural Type-II Cell Differentiation in Fetal Rat Lung

Applications of Anti-Curosurf Antibodies to Understanding the Biology of Alveolar Surfactant

Differential Regulation of Glucocorticoid Receptor Expression by Ligand in Fetal Rat Lung Cells

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