Corticotropin-releasing hormone in health and disease: an update

Abstract

Corticotropin-releasing hormone (CRH) was initially sequenced and identified in 1981, and has since become established as the principal organizer of the stress response. It causes activation of the pituitary-adrenal axis, behavioural arousal, sympathetic stimulation and a decrease in appetite. In vitro studies have shown regulation of hypothalamic CRH by a variety of neuro-transmitters, including the cytokines interleukin-1 and interleukin-6. However, circulating CRH is mainly derived from extra-hypothalamic sites, and levels may be elevated in patients with tumours secreting ectopic CRH. The placenta is a further source of CRH, which may be specifically raised in patients with pre-eclampsia, and could be a factor in the initiation of parturition. The recently identified CRH binding protein may play a vital role in this process. Clinically, CRH testing has become extremely useful in the diagnosis and differential diagnosis of Cushing's syndrome, and particularly for the localization of ACTH following inferior petrosal sinus catheterization. There is considerable evidence that many patients with depressive illness may have a disturbance of the central control of CRH, and this may be become of increasing importance in the therapy of this common condition. There are also intriguing new data suggesting that abnormalities in CRH regulation may be involved in the pathogenesis of inflammatory arthritis.