Combined administration of human corticotropin-releasing factor and lysine vasopressin induces cortisol escape from dexamethasone suppression in healthy subjects

Inadequate suppression of plasma cortisol after 1-2 mg dexamethasone is frequently observed in depressive patients. To further investigate the pathophysiology underlying cortisol nonsuppression after dexamethasone we compared cortisol and corticotropin (ACTH) response to human corticotropin-releasing factor (h-CRF), lysine vasopressin (LVP), and a concurrent administration of both peptides after pretreatment with 1.5 mg dexamethasone in six male controls. Neither h-CRF nor LVP were able to produce a marked elevation of dexamethasone suppressed plasma cortisol and ACTH. If both peptides were administered in combination, a substantial escape of plasma cortisol from dexamethasone suppression was observed. ACTH responses changed in concordance with those of cortisol indicating that the LVP-CRF interaction takes place at the pituitary level. Our finding is consistent with a multihormonal control of pituitary-adrenal activity and bears several implications for interpretation of dexamethasone suppression test results in depressive illness.     

Use of spectral analysis to test hypotheses on the origin of pinnipeds

The evolutionary origin of the pinnipeds (seals, sea lions, and walruses) is still uncertain. Most authors support a hypothesis of a monophyletic origin of the pinnipeds from a caniform carnivore. A minority view suggests a diphyletic origin with true seals being related to the mustelids (otters and ferrets). The phylogenetic relationships of the walrus to other pinniped and carnivore families are also still particularly problematic. Here we examined the relative support for mono- and diphyletic hypotheses using DNA sequence data from the mitochondrial small subunit (12S) rRNA and cytochrome b genes. We first analyzed a small group of taxa representing the three pinniped families (Phocidae, Otariidae, and Odobenidae) and caniform carnivore families thought to be related to them. We inferred phylogenetic reconstructions from DNA sequence data using standard parsimony and neighbor-joining algorithms for phylogenetic inference as well as a new method called spectral analysis (Hendy and Penny) in which phylogenetic information is displayed independently of any selected tree. We identified and compensated for potential sources of error known to lead to selection of incorrect phylogenetic trees. These include sampling error, unequal evolutionary rates on lineages, unequal nucleotide composition among lineages, unequal rates of change at different sites, and inappropriate tree selection criteria. To correct for these errors, we performed additional transformations of the observed substitution patterns in the sequence data, applied more stringent structural constraints to the analyses, and included several additional taxa to help resolve long, unbranched lineages in the tree. We find that there is strong support for a monophyletic origin of the pinnipeds from within the caniform carnivores, close to the bear/raccoon/panda radiation. Evidence for a diphyletic origin was very weak and can be partially attributed to unequal nucleotide compositions among the taxa analyzed. Subsequently, there is slightly more evidence for grouping the walrus with the eared seals versus the true seals. A more conservative interpretation, however, is that the walrus is an early, but not the first, independent divergence from the common pinniped ancestor.      

Acute adrenocortical stimulation by recombinant gamma interferon in human controls

We examined the effect of 20 micrograms recombinant gamma-interferon (rec-gamma-IFN) upon corticotropin (ACTH) and cortisol secretion in 10 healthy male controls. We observed that rec-gamma-IFN enhances cortisol secretion with maxima around 3 hours after injection of the test dose. This effect was suppressible by a single dose of 1.5 mg dexamethasone and was not associated with increased ACTH secretion. Rec-gamma-IFN also failed to enhance ACTH secretion from a pituitary cell culture. From these data we conclude that rec-gamma-IFN acts on lymphoid cells which in turn release a yet unidentified substance that directly activates the adrenocortex in a feedback controlled manner.     

Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor I in adult men

ObjectiveLower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men.Methods and resultsFrom two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n = 330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06–1.78), p = 0.02] and two hormones [HR 2.88 (95% CI 1.32–6.29), p < 0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non-significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3–0.7%, p = 0.03).ConclusionsOur results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality.