Corticotropin-releasing hormone (CRH), the major regulator of hypothalamic-
pituitary-adrenal (HPA) axis, was first isolated due to its ability to stim
ulate the release of adrenocorticotropic hormone from the anterior pituitar
y. Later, it was also found to have also a wide spectrum of actions within
the central nervous system and the periphery. Studies with pharmacological
administration of this peptide and/or antagonists and antibody neutralizati
on techniques have yielded important information concerning the physiologic
al relevance of CRH. The development of CRH knockout mice (CRH KO) has been
an important tool for addressing the physiologic and pathologic roles of C
RH. This review describes the phenotype of CRH-deficient mice, as well as t
he use of this model to study the roles of CRH on fetal development and pos
tnatal life. The role of CRA in prenatal development and postnatal regulati
on of the HPA. axis, in activation of the reproductive system during stress
, and in modulation of the immune function will be discussed. The review co
ncludes with a comparison of CRH KO mice with other models of CRH deficienc
y. (C) 1999 Academic Press.