An indicator of cancer: downregulation of Monoamine Oxidase-A in multiple organs and species

<p>Abstract</p> <p>Background</p> <p>Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types.</p> <p>Results</p> <p>Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls.</p> <p>Conclusion</p> <p>These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.</p

Experimental brood enlargement differentially influences the magnitude of the corticosterone stress response in closely related, co-occurring songbirds

1. Rearing environments can shape offspring phenotype across taxa, yet little is known about how brood size influences hypothalamic-pituitary axis functioning, whether its expression trades off with growth, and the degree to which these -relationships vary between species. 2. We evaluated how brood size influenced nestling physiological (glucocorticoids) and somatic traits (growth), and the extent to which their relationship differed between two closely related, sympatric songbirds when experiencing identical rearing environments. Specifically, we used a cross-fostering approach to alter brood size and create an experimental gradient of nestmate competition, and then tested whether experimentally manipulated brood sizes resulted in nestlings with altered concentrations of corticosterone and whether corticosterone responses traded off with growth. 3. Nestlings of both species experienced elevated concentrations of baseline and stressor-induced corticosterone when raised in enlarged broods, relative to control and reduced broods, but neither measurement was found to trade off with growth or be linked to survival to fledging. 4. In contrast, we found divergence in the magnitude of the corticosterone stress response between species across all brood treatments, with greater stressor-induced corticosterone concentrations found in the Violet-green Swallow (Tachycineta thalassina) relative to the closely related Tree Swallow (T. bicolor). 5. Our study demonstrated that brood size can lead to changes in offspring corticosterone concentrations in swallows and that nestlings of sympatric species, even those that are closely related and ecologically similar, can diverge in their corticosterone stress response when experiencing identical rearing conditions. 6. We conclude that corticosterone appears to play a key role for balancing energetic demands that arise in the face of nestmate competition in Tachycineta swallows and that elevated concentrations of corticosterone may enhance offspring survival during challenging environmental conditions, such as when brood competition is strong

Non-invasive assessment of adrenocortical activity as a measure of stress in giraffe (Giraffa camelopardalis)

BACKGROUND : Numbers of giraffes are declining rapidly in their native habitat. As giraffe research and conservation efforts increase, the demand for more complete measures of the impact of conservation interventions and the effects of captive environments on animal health and welfare have risen. We compared the ability of six different enzyme immunoassays to quantify changes in fecal glucocorticoid metabolites (FGM) resulting from three sources: adrenocorticotropic hormone stimulation test, transport, and time of day that samples were collected. RESULTS : Two male giraffes underwent ACTH injections; all six assays detected FGM increases following injection for Giraffe 1, while only three assays detected FGM increases following injection for Giraffe 2. Consistent with other ruminant species, the two 11-oxoetiocholanolone assays (one for 11,17-dioxoandrostanes and the other for 3α,11-oxo metabolites) measured the most pronounced and prolonged elevation of FGM, while an assay for 3β,11β-diol detected peaks of smaller magnitude and duration. Both of the 11-oxoetiocholanolone assays detected significant FGM increases after transport in Giraffes 3–7, and preliminary data suggest FGM detected by the assay for 11,17-dioxoandrostanes may differ across time of day. CONCLUSIONS : We conclude the assay for 11,17-dioxoandrostanes is the most sensitive assay tested for FGM in giraffes and the assay for FGM with a 5β-3α-ol-11-one structure is also effective. 11-oxoetiocholanolone enzyme immunoassays have now been demonstrated to be successful in a wide variety of ruminant species, providing indirect evidence that 5β-reduction may be a common metabolic pathway for glucocorticoids in ruminants. As FGM peaks were detected in at least some giraffes using all assays tested, giraffes appear to excrete a wide variety of different FGM. The assays validated here will provide a valuable tool for research on the health, welfare, and conservation of giraffes.Additional file 1: Full dataset in Microsoft Excel workbook format.The Association of Friends and Supporters of Goethe University Frankfurt provided financial support for F. Sicks to travel to Vienna to analyze fecal samples and von Opel Hessische Zoostiftung supported a studentship for F. Sicks. One commercial funder [Tierpark Berlin] provided support in the form of salary for F. Sicks during data analysis and preparation of this manuscript. The specific role of this author is articulated in the ‘Author Contributions’ section.http://www.biomedcentral.com/bmcvetresam2016Anatomy and PhysiologyParaclinical Science

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Non-invasive assessment of adrenocortical activity as a measure of stress in giraffe (Giraffa camelopardalis)

Additional file 1: Full dataset in Microsoft Excel workbook format.BACKGROUND : Numbers of giraffes are declining rapidly in their native habitat. As giraffe research and conservation efforts increase, the demand for more complete measures of the impact of conservation interventions and the effects of captive environments on animal health and welfare have risen. We compared the ability of six different enzyme immunoassays to quantify changes in fecal glucocorticoid metabolites (FGM) resulting from three sources: adrenocorticotropic hormone stimulation test, transport, and time of day that samples were collected. RESULTS : Two male giraffes underwent ACTH injections; all six assays detected FGM increases following injection for Giraffe 1, while only three assays detected FGM increases following injection for Giraffe 2. Consistent with other ruminant species, the two 11-oxoetiocholanolone assays (one for 11,17-dioxoandrostanes and the other for 3α,11-oxo metabolites) measured the most pronounced and prolonged elevation of FGM, while an assay for 3β,11β-diol detected peaks of smaller magnitude and duration. Both of the 11-oxoetiocholanolone assays detected significant FGM increases after transport in Giraffes 3–7, and preliminary data suggest FGM detected by the assay for 11,17-dioxoandrostanes may differ across time of day. CONCLUSIONS : We conclude the assay for 11,17-dioxoandrostanes is the most sensitive assay tested for FGM in giraffes and the assay for FGM with a 5β-3α-ol-11-one structure is also effective. 11-oxoetiocholanolone enzyme immunoassays have now been demonstrated to be successful in a wide variety of ruminant species, providing indirect evidence that 5β-reduction may be a common metabolic pathway for glucocorticoids in ruminants. As FGM peaks were detected in at least some giraffes using all assays tested, giraffes appear to excrete a wide variety of different FGM. The assays validated here will provide a valuable tool for research on the health, welfare, and conservation of giraffes.The Association of Friends and Supporters of Goethe University Frankfurt provided financial support for F. Sicks to travel to Vienna to analyze fecal samples and von Opel Hessische Zoostiftung supported a studentship for F. Sicks. One commercial funder [Tierpark Berlin] provided support in the form of salary for F. Sicks during data analysis and preparation of this manuscript. The specific role of this author is articulated in the ‘Author Contributions’ section.http://www.biomedcentral.com/bmcvetresam2016Anatomy and PhysiologyParaclinical Science

Social behavior and communication in a herd of captive giraffe

Ph.D.Committee Chair: Terry L. Mapl

Data from: Experimental brood enlargement differentially influences the magnitude of the corticosterone stress response in closely related, co‐occurring songbirds

1. Rearing environments can shape offspring phenotype across taxa, yet little is known about how brood size influences hypothalamic-pituitary axis functioning, whether its expression trades off with growth, and the degree to which these relationships vary between species. 2. We evaluated how brood size influenced nestling physiological (glucocorticoids) and somatic traits (growth), and the extent to which these relationships differed between two closely related, sympatric songbirds when experiencing identical rearing environments. Specifically, we used a cross-fostering approach to alter brood size and create an experimental gradient of nestmate competition, and then tested whether experimentally manipulated brood sizes resulted in nestlings with altered concentrations of corticosterone and if corticosterone responses traded off with growth. 3. Nestlings of both species experienced elevated concentrations of baseline and stressor-induced corticosterone when raised in enlarged broods, relative to control and reduced broods, but neither measurement was found to trade off with growth or be linked to survival to fledging. 4. In contrast, we found divergence in the magnitude of the corticosterone stress response between species across all brood treatments, with greater stressor-induced corticosterone concentrations found in the Violet-green Swallow (Tachycineta thalassina) relative to the closely related Tree Swallow (T. bicolor). 5. Our study demonstrated that brood size can lead to changes in offspring corticosterone concentrations in swallows, and that nestlings of sympatric species, even those that are closely related and ecologically similar, can diverge in their corticosterone stress response when experiencing identical rearing conditions. 6. We conclude that corticosterone appears to play a key role for balancing energetic demands that arise in the face of nestmate competition in Tachycineta swallows, and that elevated concentrations of corticosterone may enhance offspring survival during challenging environmental conditions, such as when brood competition is strong

Dryad archive data_3_sample units data

Dryad archive data_3_sample units dat

Dryad archive data_1_metadata

Dryad archive data_1_metadat

Dryad archive data_2_individuals data

Dryad archive data_2_individuals dat