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M J Odom

Publications and source records attributed to M J Odom.

7 recordsLinked to original sources
PubMed1991

Developmental and hormonal regulation of surfactant protein A (SP-A) gene expression in fetal lung.

Pulmonary surfactant is a developmentally-regulated lipoprotein synthesized and secreted by the type II cells of the pulmonary alveolus where surfactant glycerophospholipids and proteins act to reduce surface tension at the alveolar air-liquid interface. Surfactant protein A (SP-A), the major surfactant-associated protein, appears to serve an important role in surfactant function and reutilization by type II cells. SP-A synthesis and gene expression are initiated in fetal lung tissue in concert with the developmental induction of surfactant glycerophospholipid synthesis. In studies using midtrimester human fetal lung explants maintained in organ culture, we have observed that cyclic AMP and glucocorticoids have pronounced effects on morphologic development and on the levels of SP-A gene expression. Cyclic AMP analogues act primarily to induce SP-A gene transcription; whereas, glucocorticoids have complex effects at both the transcriptional and posttranscriptional levels. We also have found that human fetal lung in vitro secretes into the culture medium relatively large amounts of prostaglandins (PG) PGE2 and PGF2 alpha and the PGI2 and thromboxane A2 metabolites, 6-keto-PGF1 alpha and TxB2, respectively. The prostaglandin synthesis inhibitor, indomethacin, markedly inhibits SP-A gene expression and cyclic AMP formation by human fetal lung in culture; the inhibitory effect of indomethacin on SP-A gene expression can be prevented by simultaneous incubation with either Bt2cAMP or PGE2. These findings are suggestive that prostaglandins acting through cyclic AMP also may serve an important role in the regulation of SP-A gene expression in human fetal lung tissue.

Cell Differentiation↗
PubMed1990

The effect of gonadotropin-releasing hormone agonists on growth hormone secretion in adult premenopausal women.

Suppression of the pituitary-gonadal axis by the administration of gonadotropin-releasing hormone agonists (GnRH-a) has been used for a variety of endocrinological and gynecological disorders. The suppressive effect of GnRH-a on luteinizing hormone, follicle-stimulating hormone, and sex steroid production is well documented. However, little is known regarding the effect of GnRH-a on other aspects of pituitary function. The purpose of the present study was to determine the effect of GnRH-a treatment on growth hormone-releasing hormone (GH-RH)-stimulated GH release in premenopausal women. Eight control women and seven women, who were receiving a GnRH-a, were recruited. Before and after a bolus infusion of human GH-RH, blood samples were obtained over 3 hours and analyzed for GH by immunoassay. Basal GH and insulin-like growth factor levels were not statistically different between the two groups. However, basal levels of estradiol and the integrated GH response after GH-RH were significantly lower in the GnRH-a treated women. The reduction in GH-RH-stimulated GH release in GnRH-a treated women may be attributed to diminished endogenous estrogen secretion, or to direct pituitary suppression by GnRH-a, or both.

Adult↗
PubMed1989

Effect of oral contraceptives on adrenocorticotropin and growth hormone secretion following CRH and GHRH administration.

Previous investigations have demonstrated that basal ACTH plasma levels are reduced and that GH levels are either increased or unchanged in women taking oral contraceptives. The purpose of the present investigation was to determine the secretion of ACTH and GH following an intravenous infusion of human corticotropin releasing hormone (CRH) and human growth hormone releasing hormone (GHRH) in control women (N = 8) and in women taking a triphasic oral contraceptive (N = 9). The studies were initiated between 7:00 and 9:00 a.m. and all women were fasting. An intravenous catheter attached to a 3-way stopcock was used for blood sampling and to inject a bolus of CRH and GHRH (1 microgram/kg). Plasma samples were frozen immediately and stored at -70 degrees C until assayed for content of ACTH and GH by radioimmunoassay. The plasma levels of ACTH and GH increased following infusion of CRH and GHRH in all women. The mean plasma levels of growth hormone were not statistically different in oral contraceptive users compared to normal women. In contrast, ACTH plasma levels in oral contraceptive users were reduced approximately 25% overall, and significantly lower (p less than 0.04) at 120 minutes following the CRH infusion compared to controls. In conclusion, the GHRH-stimulated GH release was similar in normal women and oral contraceptive users. CRH-stimulated ACTH release was modestly reduced in oral contraceptive users compared to normal women suggesting that estrogens and progestogens may have a suppressive effect on the release of ACTH by the pituitary.

Adrenocorticotropic Hormone↗
PubMed1988

The concentration of the 35-kDa surfactant apoprotein in amniotic fluid from normal and diabetic pregnancies.

A specific, enzyme-linked immunoabsorbent assay was used to determine the concentration of the 35,000 mol wt surfactant apoprotein (SP-A) in samples of amniotic fluid obtained from nondiabetic (n = 358) and diabetic (n = 29) women. The enzyme-linked immunoabsorbent assay was performed with rabbit antibodies directed against SP-A present in lavage fluid from a patient with alveolar proteinosis. Amniotic fluid SP-A concentrations increased as a function of gestational age, from less than 3 micrograms/ml at 30-31 wk to 24 micrograms/ml at 40-41 wk, and were positively correlated with the lecithin to sphingomyelin ratio (p less than 0.01). SP-A concentrations also increased as a function of gestational age in shake test positive samples (p less than 0.05), but were unchanged in shake test-negative samples. There was no difference in the surfactant apoprotein concentration of male compared with female fetuses at any gestational age. In amniotic fluid obtained from 20 diabetic women, SP-A levels were significantly less than in nondiabetic pregnancies that were matched for gestational age and sex of the fetus (p less than 0.05). The SP-A concentrations in amniotic fluids obtained from nine women who were diabetic and hypertensive and from 10 hypertensive women were not different from matched controls. The relationships described above were valid whether the SP-A concentration was expressed per mg protein or per ml amniotic fluid. These data are suggestive that the concentration of amniotic fluid SP-A is decreased in diabetic pregnancies.

Amniotic Fluid↗
PubMed1988

Glucocorticoid regulation of the major surfactant associated protein (SP-A) and its messenger ribonucleic acid and of morphological development of human fetal lung in vitro.

In the present study we investigated the effects of dexamethasone (DEX) on the accumulation of the major pulmonary surfactant-associated protein (SP-A), a glycoprotein of about 35,000 mol wt, and on the levels of mRNA encoding this protein in human fetal lung in organ culture. In addition, the effects of DEX on the structural development of the fetal lung tissue was investigated using morphometric techniques. We observed that DEX had a biphasic effect on the accumulation of SP-A and its mRNA; at concentrations of 10(-10) and 10(-9) M, a stimulatory effect was observed, while at concentrations of 10(-8) M or greater, the glucocorticoid was markedly inhibitory. The inhibitory effect of DEX (10(-7) M) was evident at all time points of incubation and was apparent within 24 h of its addition to the medium at any time during the culture period. In addition, DEX (10(-7) M) antagonized the stimulatory effects of (Bu)2cAMP on the accumulation of SP-A and its mRNA. DEX also had pronounced effects on the morphological development of human fetal lung tissue. At a concentration of 10(-7) M or greater, DEX caused a marked reduction of alveolar lumen size compared to that of fetal lung explants maintained in control medium. A biphasic effect of DEX on the volume density of type II cells in fetal lung explants was observed; at a concentration of 10(-10) M, DEX significantly increased the volume density of type II cells, whereas at a concentration of 10(-7) M or more, the glucocorticoid significantly reduced the volume density of type II cells compared to that of control explants. These findings suggest that synthetic glucocorticoids at concentrations of 10(-10) and 10(-9) M are stimulatory whereas elevated levels are inhibitory of SP-A synthesis and morphological development of the human fetal lung.

Bucladesine↗
PubMed1987

Adenosine 3',5'-monophosphate analogs and beta-adrenergic agonists induce the synthesis of the major surfactant apoprotein in human fetal lung in vitro.

The use of beta-adrenergic agonists in the treatment of preterm labor has been found to be associated with a decreased incidence of respiratory distress syndrome (RDS) in premature newborns. beta-Sympathomimetic agents, which activate adenylate cyclase and increase tissue cAMP levels, as well as cAMP analogs stimulate surfactant glycerophospholipid synthesis and secretion by fetal lung tissue. In the present study, we used antibodies directed against the major human pulmonary surfactant apoprotein, a 35,000-dalton glycoprotein, to evaluate the effects of the cAMP analog dibutyryl cAMP (Bt2cAMP) and the beta-adrenergic agonist terbutaline on surfactant apoprotein synthesis in human fetal lung explants in organ culture. By use of immunoblot analysis, we found that Bt2cAMP (1 mM) markedly stimulated accumulation of the major surfactant apoprotein in human fetal lung explants, as did terbutaline. Bt2cAMP treatment also increased the relative rate of incorporation of [35S]methionine into the major surfactant apoprotein. The Bt2cAMP-induced increase in surfactant apoprotein synthesis and accumulation was associated with an increase in the levels of translatable surfactant apoprotein mRNA. Morphometric analysis at both the light and electron microscopic levels was used to evaluate the effects of Bt2cAMP on the morphology of the human fetal lung in vitro. After 48-h incubation with Bt2cAMP, the prealveolar ducts of the fetal lung explants were enlarged greatly, and the relative amount of interalveolar connective tissue was reduced compared to those in control tissues. The volume density of type II cells in the Bt2cAMP-treated explants was significantly greater than that in control explants at this time point; however, after 4 and 6 days of incubation, the volume density of type II cells in control and Bt2cAMP-treated tissues was similar, and the lumina of the prealveolar ducts of control tissues had a volume density similar to that of Bt2cAMP-treated explants. Bt2cAMP also had pronounced effects on the ultrastructural morphology of the human fetal lung explants. Large quantities of secreted lamellar bodies and tubular myelin were observed in the lumina of the prealveolar ducts of the Bt2cAMP-treated tissue. Few lamellar bodies and no tubular myelin were observed in the lumina of the prealveolar ducts of control tissues. These findings suggest that cAMP may serve an important regulatory role in the synthesis and secretion of the major surfactant apoprotein by human fetal lung.

1-Methyl-3-isobutylxanthine↗