The “homeostasis hormone” and its CRF1 receptor. From structure to function

Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

“…This question has become critical in the context of the study of inflammatory processes related with the metabolic syndrome. Obesity is widely accepted to be directly related to increased glucocorticoid activity [10], but direct measurement of cortisol or corticosterone (or those of their main excretion products) do not show definite increases in their circulating levels [36]. Since we have observed the existence of an additional steroid hormone reservoir pool in blood, i.e.…”

“…Glucocorticoids also hamper the inflammatory immune response [2], induce insulin resistance [3], [4], enhance overall lipogenesis and fat deposition [5], and increase the liver glucose output [6], usually at the expense of amino acids [7]. Glucocorticoids waste body protein [8] and minerals [9], and there is a generalized consensus that their activity is increased in the metabolic syndrome [10]. Nevertheless, glucocorticoid excretion is more related to stress and stress-related conditions [11] than to obesity and diabetes, which usually show normal circulating serum levels [12].…”

“…Since the case of glucocorticoids is more complex we decided to determine whether sex and/or diet, affect the compartmentation/transport of blood glucocorticoids. The objective was to find whether the known increased glucocorticoid effects observed in the metabolic syndrome [30] are a consequence of modified CBG levels [30], [31], CBG affinity [32] or compartmentation, since the changes observed in serum circulating levels or cortisol excretion could not fully explain the effects observed [10]. We used a rat model because the variables of diet, sex, age and stress could be more easily controlled, and we had access to fresh liver tissue, despite the main glucocorticoid in rodents being corticosterone and not cortisol as in humans.…”

Non-peptide ligands in the characterization of peptide receptors at the interface between neuroendocrine and mental diseases

“…Furthermore, effort is directed to potential therapeutics, prevention and diagnostics of obesity-related disorders. Many of feeding-related receptor agonists act not only in the hypothalamus but also in extrahypothalamic, telencephalic, mesencephalic and metencephalic areas thereby contributing to the regulation of behavior, as has been confirmed by numerous studies [5,[7][8][9][10][11][12][13][14][15][16][17]. Consequently, rising attention is paid to ligands of feeding-related GPCRs as potential tools for the investigation of their role in behavioral disturbances.…”

Διαλεύκανση Της Δομής Της Τρίτης Διαμεμβρανικής Περιοχής Του Τύπου 1 Υποδοχέα Του CRF, Καθώς Και Των Αλληλεπιδράσεών Του Με Τον CRF Και Των Αναλόγων Του

“…Από τότε ακολούθησαν πολυάριθμες μελέτες που σχεδίασαν και συνέθεσαν μικρομοριακούς ανταγωνιστές των υποδοχέων του CRF όπως ανάλογα κινολινών και ισοκινολινών, πυριμιδινών, πυριδινών, πυράζολο-πυριμιδινών και πουρινών (195)(196)(197)(198)(199)(200)(201)(202). Κοινό δομικό χαρακτηριστικό των μη πεπτιδικών CRF ανταγωνιστών είναι ένας κεντρικός, επίπεδος, ετεροκυκλικός δακτύλιος (Εικόνα 1.6) (39,203).…”