Hypoxia and the hypoxia inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription.

Overactivation of the cAMP signal transduction pathway plays a central role in the pathogenesis of endocrine tumors. Genetic aberrations leading to increased intracellular cAMP or directly affecting PKA subunit expression have been identified in inherited and sporadic endocrine tumors, but are rare indicating the presence of nongenomic pathological PKA activation. In the present study, we examined the impact of hypoxia on PKA activation using human growth hormone (GH)-secreting pituitary tumors as a model of an endocrine disease displaying PKA-CREB overactivation.

GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours.

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease.

Recent advances in understanding corticotroph pituitary tumor initiation and progression.

Cushing's disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop sporadically and only a limited number of corticotroph adenomas have been found to be associated with different neuroendocrine syndromes or with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the presence of ubiquitin-specific protease 8 mutations on the other hand partially explained the causes of their development.

Physical Exercise and Spatial Training: A Longitudinal Study of Effects on Cognition, Growth Factors, and Hippocampal Plasticity.

Physical exercise has been suggested to improve cognitive performance through various neurobiological mechanisms, mediated by growth factors such as BDNF, IGF-I, and VEGF. Moreover, animal research has demonstrated that combined physical and cognitive stimulation leads to increased adult neurogenesis as compared to either experimental condition alone. In the present study, we therefore investigated whether a sequential combination of physical and spatial training in young, healthy adults elicits an additive effect on training and transfer gains.