Fetal Mouse Lung Ultrastructural Maturation Is Accelerated by Maternal Thyrotropin-Releasing Hormone Treatment

Devaskar, Uday; Govindrajan, R.; Heyman, Sarah; Sosenko, Ilene R.S.; deMello, Daphne E.

doi:10.1159/000244354

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…2, D and E). Incidental examples of LBs within the glycogen-rich zones have often been reported without major discussion (14,16,30,34,38,47). Clearly, the glycogen stores do not represent a barrier to LBs or at least some types of lipid-rich structures.…”

Section: Resultsmentioning

confidence: 99%

Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells

Ridsdale

Post

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary surfactant is a lipoprotein complex that functions to reduce surface tension at the air liquid interface in the alveolus of the mature lung. In late gestation glycogen-laden type II cells shift their metabolic program toward the synthesis of surfactant, of which phosphatidylcholine (PC) is by far the most abundant lipid. To investigate the cellular site of surfactant PC synthesis in these cells we determined the subcellular localization of two key enzymes for PC biosynthesis, fatty acid synthase (FAS) and CTP:phosphocholine cytidylyltransferase-␣ (CCT-␣), and compared their localization with that of surfactant storage organelles, the lamellar bodies (LBs), and surfactant proteins (SPs) in fetal mouse lung. Ultrastructural analysis showed that immature and mature LBs were present within the glycogen pools of fetal type II cells. Multivesicular bodies were noted only in the cytoplasm. Immunogold electron microscopy (EM) revealed that the glycogen pools were the prominent cellular sites for FAS and CCT-␣. Energy-filtering EM demonstrated that CCT-␣ bound to phosphorus-rich (phospholipid) structures in the glycogen. SP-B and SP-C, but not SP-A, localized predominantly to the glycogen stores. Collectively, these data suggest that the glycogen stores in fetal type II cells are a cellular site for surfactant PC synthesis and LB formation/maturation consistent with the idea that the glycogen is a unique substrate for surfactant lipids.CTP:phosphocholine cytidylyltransferase; pulmonary surfactant; immunogold; fatty acid synthase SHORTLY BEFORE BIRTH, alveolar type II cells must increase their surfactant lipid and protein synthesis to generate sufficient pulmonary surfactant. This material reduces the surface tension at the air/liquid interface and ample amounts are required to prepare the lung for extrauterine life (30). Surfactant production appears to be a carefully timed event because a preterm infant can experience respiratory distress and atelectasis as a direct result of pulmonary surfactant insufficiency.Pulmonary surfactant is composed of a mixture of lipids and proteins. The most abundant lipid species is phosphatidylcholine (PC) with dipalmitoyl-PC being the surface-active reagent (17). Whereas alveolar type II cells in the postpartum lung need to synthesize lipids and proteins for pulmonary surfactant maintenance, the fetal type II cells need to generate enough material to establish a functioning air-liquid barrier immediately at birth (10, 29). It is evident that the surge of production of surfactant at late fetal gestation is a daunting metabolic task for the type II cells. Morphologically, large amounts of glycogen accumulate in the distal undifferentiated epithelium before surfactant synthesis, and these glycogen stores are depleted as surfactant is synthesized (6, 32). Biochemically, temporal relationships between glycogen and phospholipids (5, 7) have suggested that glycogen is used as a carbon source to generate the glycerol backbone and acyl chains of the surfactant lipids, but a direct precu...

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Section: Resultsmentioning

confidence: 99%

Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells

Ridsdale

Post

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Thyrotropin-Releasing Hormone Accelerates Fetal Mouse Lung Ultrastructural Maturation via Stimulation of Extra Thyroidal Pathway

et al. 1997

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Maternal administration of TSH-releasing hormone (TRH) in the euthyroid mouse accelerates fetal lung ultrastructural maturation. However, the mechanism(s) of TRH in fetal lung development remains unclear; it could be due to its neuroendocrine and/or neurotransmitter effects. Although the neuroendocrine effect of TRH is mediated via stimulation of the fetal pituitary-thyroid axis, the neurotransmitter effect is mediated via stimulation of fetal autonomic nervous system activity. In the hyt/hyt mouse there is a point mutation in the beta subunit of the TSH receptor in the thyroid gland of the Balb-c mouse. In these mice TSH does not bind to its receptors, leading ultimately to the development of primary hypothyroidism, which is transmitted as an autosomal recessive trait. A maturational delay in the lung ultrastructure of the hyt/hyt mouse fetus has been observed. This investigation was undertaken to study the effect of maternal TRH treatment on lung ultrastructural maturation in the hyt/hyt mouse fetus. If the effect of TRH is mediated via stimulation of fetal pituitary-thyroid axis, TRH treatment should not enhance lung maturity in the hyt/hyt fetus and vice versa. Adult hyt/hyt mice made euthyroid by triiodothyronine supplementation were mated to carry hyt/hyt pups. Saline or TRH (0.4 or 0.6 mg/kg/dose) was administered to the mother (i.p.) on d 16 and 17 (b.i.d.) and on d 18 of pregnancy 1 h before killing (term, approximately 20 d). The fetal lung electron micrographs were subjected to ultrastructural morphometric analysis of the number of lamellar bodies and glycogen/nuclear ratio in type II cells, and the alveolar/parenchymal ratio by Chalkley point counting with an interactive computerized image analyzer (Optimas, Bioscan). Fetal lungs exposed to the lower dose of TRH (n = 7) showed no significant difference in their ultrastructural maturation when compared with saline-treated controls (n = 5). However, fetal lungs exposed to a higher dose of TRH (n = 6) showed increased numbers of lamellar bodies per type II cell, an increase in the alveolar/parenchymal ratio, larger air spaces, thinner alveolar septa, presence of tubular myelin, and increased numbers of air-blood barriers. We conclude that the effect of TRH in accelerating fetal mouse lung maturation is at least in part mediated via stimulation of extra thyroidal pathways.

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Fetal Mouse Lung Ultrastructural Maturation Is Accelerated by Maternal Thyrotropin-Releasing Hormone Treatment

Cited by 2 publications

References 14 publications

Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells

Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells

Thyrotropin-Releasing Hormone Accelerates Fetal Mouse Lung Ultrastructural Maturation via Stimulation of Extra Thyroidal Pathway

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