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This paper has integrated new and past data to elucidate how lipid, protein and glycogen metabolism contribute to generating the ATP required by the southern hemisphere lamprey Geotria australis during its ~ 13-15 months, non-trophic upstream spawning migration. Energy is required for maintenance, swimming, the development of gonads and secondary sexual characters and spawning and post-spawning activities. Plasma and muscle metabolites were measured in animals subjected to an exercise-recovery regime at the commencement and completion of the spawning run. The present study demonstrated the following. At all stages of the migration, plasma glucose and glycerol concentrations increased during exercise and then declined, whereas plasma FFAs exhibited the reverse trend. During exercise and recovery, alanine declined and ammonia increased in the plasma of early migrants, while the opposite occurred in mature males. Following exercise, muscle alanine rose and then declined in early migrants, but declined and then rose in mature males. The composite data emphasise that, while the same catabolic processes are employed by both sexes early in the migration, when animals are immature, they differ markedly between the sexes as they mature and then spawn, reflecting their different demands. Energy is supplied predominantly via anaerobic metabolism in early migrants, but by anaerobic and aerobic metabolism in prespawning females and by aerobic metabolism in mature males and spent females. Although proteolysis is limited early in the migration, it is employed extensively during maturation and particularly by females, which undergo a substantial reduction in length in the lead-up to spawning.

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Glucocorticoid induction of pulmonary surfactant involves a mesenchyme-derived protein first characterized in 1978 by Smith and termed fibroblast-pneumocyte factor (FPF). Despite a number of agents having been postulated as being FPF, its identity has remained obscure. In the past decade, three strong candidates for FPF have arisen. This review examines the evidence that keratinocyte growth factor (KGF), leptin or neuregulin-1ß (NRG-1ß) act as FPF or components of it. As with FPF production, glucocorticoids enhance the concentration of each of these agents in fibroblast-conditioned media. Moreover, each stimulates the synthesis of surfactant-associated phospholipids and proteins in type II pneumocytes. Further, some have unique activities, for example, KGF also minimizes lung injury through enhanced epithelial cell proliferation and NRG-1ß enhances surfactant phospholipid secretion and ß-adrenergic receptor activity in type II cells. However, even though these agents have attributes in common with FPF, it is inappropriate to specify any one of these agents as FPF. Rather, it appears that each contributes to separate mesenchymal-epithelial signaling mechanisms involved in different aspects of lung development. Given that the production of pulmonary surfactant is essential for postnatal survival, it is reasonable to suggest that several mechanisms independently regulate surfactant synthesis.

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It is well established that glucocorticoids elevate the production of fibroblast-pneumocyte factor (FPF), which induces type II cells to synthesize surfactant phospholipids. FPF, however, has not been identified and it is not clear whether it is a single factor or a complex mixture of factors. In this study it has been shown that, when lung fibroblasts are exposed to dexamethasone, the concentration of neuregulin-1ß (NRG1ß) in conditioned medium is elevated 2-fold (P<0.05), even though NRG1ß gene expression is unaffected. This, together with the finding that exposure of type II cells to NRG1ß directly stimulates by 3-fold the rate of phospholipid synthesis (P<0.05), suggests that NRG1ß is a component of FPF that promotes lung development.

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Glucocorticoids induce lung fibroblasts to produce fibroblast-pneumocyte factor, a peptide that stimulates type II cells to synthesize pulmonary surfactant. This effect is known to be more apparent in cells derived from female fetuses, a characteristic that has been attributed to sex-linked differences in the fibroblasts. In the current study, it has been shown that dexamethasone enhances both ß-adrenergic receptor (ß-AR) activity (1.3- to 1.6-fold increase) and (-)-isoproterenol-induced secretion of surfactant (1.8- to 1.9-fold increase) in type II cells. However, fibroblast-conditioned media (FCM), prepared in the presence of dexamethasone, generates a much greater response to (-)-isoproterenol (3.1- to 3.8-fold increase). Furthermore, each of these effects is more pronounced if both cell types are female-derived. It is hypothesized that the enhanced response to glucocorticoids is the result of a synergistic effect between the steroid and a component of FCM. Neuregulin-1ß (NRG1ß), which is elevated in FCM generated in the presence of dexamethasone, influences not only the rate of surfactant secretion and the ß-AR activity in type II cells, but also enhances in both sexes the cellular response to (-)-isoproterenol. These results suggest that NRG1ß might be more effective than glucocorticoids in treating prematurely born male infants, which are known to respond poorly to glucocorticoids. Given that glucocorticoids are known to induce higher levels of ß-AR mRNA, the effect of NRG1ß, alone and in combination with dexamethasone, on ß-AR gene expression was measured using qRT-PCR. Whereas NRG1ß had no effect alone, in combination with dexamethasone it produced up to a 4.2-fold elevation in the level of ß-AR mRNA.

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Type II pneumocytes are responsible for the synthesis and secretion of pulmonary surfactant, which reduces surface tension in lung alveoli, thus decreasing their tendency to collapse during expiration. For this effect to be sustained, the integrity of the surface-active components of surfactant must be maintained. This study has shown that, when cultured type II pneumocytes are exposed to lipoprotein-free serum (LFS), the level of lyso-phosphatidylcholine (lyso-PC) in the secreted surfactant phospholipids is markedly elevated with a concomitant decline in the level of phosphatidylcholine (PC). This effect is the result of hydrolysis of surfactant PC by a phospholipase A(2) (PLA(2))-like activity present within serum. Anion-exchange chromatography, gel filtration chromatography and preparative electrophoresis of human LFS have shown that this PLA(2)-like activity coelutes with albumin and is biochemically distinct from the secretory form of PLA(2). Furthermore, specific inhibitors of PLA(2) such as p-bromophenacyl bromide, aristolochic acid, and palmitoyl trifluoromethyl ketone do not inhibit this activity of serum. Commercially purified human serum albumin fraction V and recombinant human serum albumin (rHSA) are almost as effective as LFS in enhancing the level of lyso-PC in the media. The latter finding implies that rHSA directly generates lyso-PC from secreted PC and suggests that this PLA(2)-like activity may be an intrinsic attribute of albumin.

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