Glucocorticoids are a class of systematically secreted hormones, vital for mammalian life, which are intensively investigated for more than 80 years. They regulate multiple body processes like metabolism, fluid homeostasis, immune and stress system responsivity, as well as brain function. Glucocorticoids have a complex rhythm by which they are released to circulation from the adrenal cortex. The hormone exhibits a circadian variation, with high hormonal levels being secreted just prior and during the active part of the day, and progressively lower and lower amounts being released during the inactive part of it. Underlying this diurnal variation there is a more dynamic, ultradian rhythm composed of frequent episodes of glucocorticoid secretion (hormonal pulses). Accumulating evidence from observational, in silico, in vitro and in vivo, preclinical and clinical studies suggest that both aspects of glucocorticoid rhythmicity are preserved among mammalian species and are important for brain function. The central nervous system is exposed to both aspects of the hormonal rhythm and has developed mechanisms able to perceive them and translate them to differential cellular events, genomic and non-genomic. Thus, glucocorticoid rhythmicity regulates various physiological neural and glial processes, under baseline and stressful conditions, and hormonal dysrhythmicity has been associated with cognitive and behavioural defects. This raises a number of clinical implications concerning (i) glucocorticoid involvement in neuropsychiatric disease and (ii) improving the therapeutic efficacy or expanding the role of glucocorticoid-based treatments in such conditions.
Konstantinos Kalafatakis, Georgina M Russell and Stafford L Lightman
Mark R. Johnson, Mark Bower, Jonathan R. Seck and Stafford L. Lightman
In animals, there is sexual dimorphism of both neurohypophysial peptide secretion in response to stressful stimuli and to the inhibitory effects of opioids. In men, endogenous opioids inhibit the release of oxytocin when AVP secretion is stimulated by insulin-induced hypoglycemia. We have now investigated the role of endogenous opioids in the AVP and oxytocin response to insulin-induced hypoglycemia in women. Twelve subjects, 6 in the follicular and 6 in the luteal phase of the menstrual cycle, were infused on 2 occasions with naloxone (4 mg bolus and 6 mg/h) or saline. Soluble insulin (Human Actrapid®, 0.15 μ/kg, iv) was given and serial blood samples taken. Blood sugar fell significantly (p<0.05) and similarly in all groups. In the follicular phase hypoglycemia led to a rise in plasma AVP from 1.3 ± 0.2 to 1.8 ± 0.2 pmol/l in the saline-infused subjects (NS), and from 1.0 ± 0.1 to 2.0 ± 0.2 pmol/l in the naloxone-infused (p<0.05). AVP rose similarly from 0.6 ± 0.1 to 1.6 ± 0.5 pmol/l (p<0.05) in the luteal phase controls and from 0.8 ± 0.1 to 1.5 ± 0.3 pmol/l (p<0.05) in naloxone-infused subjects in the luteal phase. There were no significant differences between any of these groups. There were no significant changes in plasma oxytocin in any group. We therefore conclude that in women, unlike men, endogenous opioids do not modulate oxytocin or vasopressin release during insulin-induced hypoglycemia.