ACTH (18-39) (human)

An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

Objectives:Adrenal insufficiency is often diagnosed by short synacthen test using intravenous Injection Synacthene, which is not marketed in India officially. To overcome this problem this study was planned to validate and use Acton Prolongatum (Ferring pharmaceuticals) as intramuscular ACTH stimulation test for evaluation of adrenal function.Methods:This study was planned in two groups. First group called validation group, was studied for validation of intramuscular ACTH test and second group called study group, was evaluated for efficacy of intramuscular ACTH test to detect adrenal insufficiency. Twenty five units of ACTH (Acton Prolongatum) was injected intramuscularly and blood sample was collected after 60 minutes for estimation of cortisol. All subjects with one hour post ACTH cortisol < 18.0 microg/dl were diagnosed as having adrenal insufficiency.Results:This study was carried out in 61 subjects in validation group and 89 patients in study group. Basal and post ACTH serum cortisol were within normal range in healthy adults, patients with diabetes mellitus and primary hypothyroidism in validation group. Basal cortisol ranged from 4.67-18.39 microg/dl and post ACTH serum cortisol ranged from 20.01-44.95 microg/dl in these groups. Patients with known adrenal insufficiency had significantly low basal cortisol level than controls (2.86 +/- 2.66 vs. 10.35 +/- 4.37 microg/dl, p < 0.001), and post ACTH serum cortisol was < 18.0 microg/dl in all. Among study group 37 patients (41.6%) were diagnosed as adrenal insufficiency using post ACTH cortisol levels. Basal cortisol (< 3.0 microg/dl) could detect only 60% of these patients. Basal cortisol level has sensitivity of 60% and specificity of 100% to detect AI when compared to ACTH stimulated cortisol levels.Conclusion:Intramuscular ACTH test using Acton Prolongatum is effective in evaluation of adrenal function in all suspected cases of primary or secondary adrenal insufficiency. Basal cortisol has poor sensitivity to diagnose AI.

Serotonin (5-HT) is involved in sleep in two different ways. First, when released during waking by the axonal nerve endings, it influences the synthesis of hypnogenic substances in specific brain targets. Such a synthesis might be in keeping with the waking qualitative aspects. As an example, the hypnogenic CLIP peptide (ACTH18-39) is synthesized when stressful events occur during wakefulness. Second, when released during sleep within the nucleus raphe dorsalis (nRD) by dendrites of 5-HT neurons, it contributes to 5-HT perikarya silencing through an auto-inhibitory process. Nitric oxide, co-synthesized with 5-HT, may act in synergy with this amine at both mentioned levels. Regarding the triggered hypnogenic substances, they induce sleep through acting on two components within the nRD: (1) the 5-HT component; its silencing is necessary to remove the gating effect exerted on phasic sleep events (ponto-geniculo-occipital, PGO, waves); (2) a substance P component; its silencing is necessary, at least, to alleviate the tonic influence exerted on somatic muscles. These two components may constitute the brain "sleep switch-on" mechanism allowing wake/sleep alternation. Pharmacological procedures influencing this switch may be determinant for treating insomniac patients. Serotonin appears thus to be involved in sleep preparation, triggering and maintenance.