Corticotropin-Releasing Hormone

Hormones are the body's chemical messengers that travel through the blood stream to various tissues, working slowly over time to affect a variety of processes. Corticotropin releasing hormone (CRH) is [Page 167]a 41-amino acid peptide hormone that is made and released by the hypothalamus gland. After its release, CRH travels to the anterior lobe of the pituitary gland where it stimulates the release of corticotropin. Corticotropin increases the production of CRH-related peptides from the adrenal cortex, which interact with CRH1 and CRH2 G-protein coupled receptors throughout the body during the stress response. It is believed that this hormone system may play an important role in energy balance.

Studies have shown that CRH administration prevents weight gain in obese (but not lean) rats. This observation suggests that CRH may be reduced in obesity. CRH also lowers the body weight at which food-deprived animals begin to store food. CRH-related peptides are anorectic agents that decrease food intake. Some of these peptides are also thermogenic, increasing energy expenditure through activity of the sympathetic nervous system. The mechanisms of these anorectic and thermogenic effects are the focus of many studies.

Selectively inhibiting the CRH2 receptor has been shown to block the anorectic effect of CRH, demonstrating that it plays a part in anorexia. The role of the CRH1 receptor is unclear; however, studies suggest that it may also contribute to the anorectic effect of the CRH system. Additionally, the CRH1 receptor may play a role in CRH-related thermogenesis. Other studies have shown that CRH antagonists can block the anorectic effect of leptin, a hormone that promotes the feeling of fullness after a meal. This observation suggests that there may be a relationship between the CRH system and leptin.

Since these hormones may be involved in energy balance, the CRH system is being viewed as a potential target for antiobesity drugs. Nonspecific activation of this system may lead to other undesirable effects; however, recent studies on the CRH1 and CRH2 ligands may allow for the development of drugs that are specific to energy balance in the future.