Clayton Foundation Laboratories for Peptide Biology
Catherine Rivier, a professor in The Clayton Foundation Laboratories for Peptide Biology, studies hormones that shuttle messages between the periphery and the brain. Specifically, she investigates how the brain perceives and responds to external stressors, such as infection, exposure to psychological threats, or alcohol. Her laboratory has identified some of the mechanisms through which the occurrence of stressors is conveyed to specialized areas of the brain.
For example, Rivier's team has shown that rodents exposed to alcohol during embryonic development release excessive levels of corticotropin-releasing factor, a brain hormone associated with stress, as well as elevated adrenal responses to stressors, when they reach adulthood. If similar changes take place in humans, they could trigger pathologies related to fetal alcohol syndrome, including anxiety, attention deficit disorder and increased infections. Furthermore, Rivier and her colleagues have shown that exposure to alcohol during adolescence also causes permanent changes in the brain areas connected to responses to stressors, which may participate in the development of drug abuse in adulthood. Finally, Rivier's team has identified a new pathway through which the brain controls the activity of the testes. This discovery, which changes the way we understand the control of male reproductive functions, may offer insights into some puzzling cases of low testosterone secretion connected to stressors or diseases.
The health of mammals depends on their ability to maintain the internal environment of their bodies within narrow and clearly defined limits in the face of physiological or psychological threats. Challenges to the body's homeostasis—whether perceived or real—are handled by the hypothalamicpituitary- adrenal (HPA) axis, which involves the interaction of the brain structure known as the hypothalamus, the pituitary gland (just below the hypothalamus) and the adrenal glands (at the top of the kidneys). Together, these three organs control reactions to stress and regulate many body processes, including digestion, the immune system, mood and emotions, sexuality, as well as energy storage and expenditure.
Alcohol is one of the stimuli that activate the HPA axis in rodents, but the mechanisms responsible for it are not yet fully understood. Rivier's laboratory had shown earlier that the peptide corticotropin-releasing factor (CRF), which is produced in the hypothalamus, was essential for an appropriate HPA axis response to acute alcohol. While the ultimate effect of alcohol is the binding of CRF to specific receptors on pituitary cells, and the ensuing release of ACTH and adrenal steroids, recent experiments by Rivier and her team revealed a more complex picture of alcohol's action on the brain. They found that alcohol increases the activity of dopamine b-hydroxylase, the enzyme directly responsible for the synthesis of norepinephrine. The latter contributes to the HPA axis's response to alcohol, and this knowledge may help the development of specific therapies that counteract some of the deleterious effects of this drug.
Stress is thought to play a role in the ability of addicted individuals to maintain abstinence. Thus, a better understanding of the function of the HPA axis during the development of alcohol dependence, and how the activity of this axis differs between dependent and non-dependent animals, will be helpful in pursuing novel therapies for the treatment of alcohol addiction.