The data presented with the isolated adrenal cells, in the present study, show that adrenocorticotropin in the physiological concentration range stimulates the synthesis of guanosine 3' : 5'-monophosphate (cyclic GMP), protein kinase activity, and steroidogenesis in a concentration-dependent manner without detectable rise in the levels of adenosine 3': 5'-monophosphate (cyclic AMP). Millimolar concentrations of cyclic AMP and cyclic GMP, which stimulate corticosterone synthesis, also activate kinase activity and steroidogenesis in a sigmoid concentration-response manner. The process of phosphorylation activated by corticotropin, cyclic AMP and cyclic GMP is not inhibited by cycloheximide or actinomyin D. It is therefore proposed that the hormonal responses mediated by cyclic GMP and cyclic AMP are via the protein kinase enzymatic steps, and the inhibitory effect of cycloheximide and actinomycin D in corticotropin-stimulated steroidogenesis follows this step. In conjunction with our previous observations that the biosynthetic steps from (20S)-20-hydroxycholesterol to corticosterone are neither inhibited by cycloheximide nor affected by cyclic GMP, it is inferred that the rate-limiting step of adrenal steroidogenesis is the transformation of cholesterol to (20S)-20-hydroxycholesterol and this very step is regulated by cyclic GMP and cyclic AMP.Of further significance are the findings that micromolar concentrations of cyclic AMP and cyclic GMP, which do not stimulate steroidogenesis, effectively stimulate protein kinase activity in a concentration-dependent manner. It is therefore concluded that all cyclic-nucleotide-dependent protein kinase activities of the cell are not necessarily related to steroidogenesis. Trivial Names. Pregnenolone, progesterone, deoxycorticosterone, corticosterone, 1 f /3, lated target tissue cell. The studies carried out with this model cell system have provided evidence strongly indicating that adrenocorticotropin-stimulated steroidogenesis is mediated by both cyclic GMP and cyclic CAMP ; the former nucleotide mediating the adrenocorticotropin control of corticosterone synthesis at physiological concentrations of the hormone (< 10 punits) and the latter at higher concentrations [9, 101. Additional evidence has been presented that the cyclic-GMP-regulated steroidogenic processes are unique and are not shared by cyclic AMP [9-111. The present study was designed to investigate the role of protein kinase in the stimulation of steroidogenesis by adrenocorticotropin, cyclic AMP, and cyclic GMP within the isolated adrenal cell and also to examine where the translation control of the hormone occurs in relation to this step.

Administering recombinant interleukin-1 beta (IL-1 beta) intratracheally caused lung neutrophil accumulation and lung injury in hamsters. The percentage of leukocytes that were neutrophils increased progressively in lavages from lungs of hamsters given 25, 50, or 100 ng IL-1 beta intratracheally 2 h before. Lung injury, reflected by increased lung lavage protein concentrations and lung lavage hemoglobin concentrations, increased 2 h after administering 100 ng IL-1 beta. Lung injury, reflected by lung wet weight/body weight ratios, followed similar patterns, with significant increases occurring 2 h after insufflating 50 or 100 ng IL-1. Our results indicate that increased concentrations of IL-1 beta in lung airways can cause neutrophil recruitment and lung injury in hamsters. This mechanism may contribute to the development of lung neutrophil accumulation and lung injury that characterizes ARDS patients who have increased airway levels of IL-1 beta.

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