Initially the hypothalamic factor responsible for the release of corticotropin (CRF), was thought to be a simple peptide. More recent work has led to the conclusion that CRF is a multifactorial complex. In 1979 we proposed that vasopressin, much disputed as a CRF candidate, was a major constituent of the complex, interacting with a potentiating the CRF activity of the other component(s). The recent characterization of a 41 residue ovine hypothalamic peptide capable of releasing adrenocorticotropic hormone (ACTH) in a dose-related manner has allowed us to compare its CRF bioactivity with that of vasopressin and simple extracts of the hypothalamus, and to investigate any interaction it may have with vasopressin and other hypothalamic factors in the release of ACTH. We report here that the new CRF is more potent than vasopressin in releasing ACTH. When given simultaneously with vasopressin a fourfold potentiation of CRF activity with steep dose-response characteristics were observed. It also potentiated vasopressin-free hypothalamic extracts, suggesting that a new CRF does not account for all the nonvasopressin portion of the CRF complex.

Studies in mammalian skin have shown expression of the genes for corticotropin-releasing hormone (CRH) and the related urocortin peptide, with subsequent production of the respective peptides. Recent molecular and biochemical analyses have further revealed the presence of CRH receptors (CRH-Rs). These CRH-Rs are functional, responding to CRH and urocortin peptides (exogenous or produced locally) through activation of receptor(s)-mediated pathways to modify skin cell phenotype. Thus, when taken together with the previous findings of cutaneous expression of POMC and its receptors, these observations extend the range of regulatory elements of the hypothalamic-pituitary-adrenal axis expressed in mammalian skin. Overall, the cutaneous CRH/POMC expression is highly reactive to common stressors such as immune cytokines, ultraviolet radiation, cutaneous pathology, or even the physiological changes associated with the hair cycle phase. Therefore, similar to its central analog, the local expression and action of CRH/POMC elements appear to be highly organized and entrained, representing general mechanism of cutaneous response to stressful stimuli. In such a CRH/POMC system, the CRH-Rs may be a central element.

Objective To investigate whether syncytiotrophoblast microvilli (STBM) are shed into the maternal circulation in increased amounts in pre-eclamptic pregnancies as a possible cause of maternal vascular endothelial dysfunction.Design A time-resolved fluoroimmunoassay was developed to measure STBM levels in peripheral and uterine venous plasma from normal pregnant and pre-eclamptic women. Three colour flow cytometry was used to assess the microparticulate nature of the STBM in pregnancy plasma. The effects of these plasmas on endothelial cell proliferation was compared and a correlation with the levels of STBM detected was sought.Setting A laboratory investigation using clinical samples obtained from an obstetric practice in a teaching hospital.Samples Peripheral venous plasma from 20 women with established pre-eclampsia, 20 normal pregnant women matched for age, gestation and parity, and 10 nonpregnant women of reproductive age. Paired uterine and peripheral venous plasma taken at caesarean section from 10 women with pre-eclampsia and 10 unmatched normal pregnant women. Results STBM were detected in the plasma of pregnant women by both flow cytometry and timeresolved fluoroimmunoassay. Significantly higher levels of STBM were found in women with established pre-eclampsia (P = 0.01). STBM concentrations were higher in uterine venous plasma than in concurrently sampled peripheral venous plasma, confirming their placental origin. A significant correlation was found between the amount of STBM in the plasma and endothelial cell inhibitory activity.Conclusions STBM are shed into the maternal circulation (microvillous deportation) and are present in significantly increased amounts in pre-eclamptic women. They may contribute to the endothelial dysfunction underlying the maternal syndrome of pre-eclampsia.

In recent studies to clone and characterize genes coding for the corticotropin-releasing factor-binding protein (CRF-BP), analysis of the tissue distribution of the CRF-BP gene indicated a high level of expression in the rat brain. We have now characterized by immunohistochemical and hybridization histochemical means the cellular localization of CRF-BP protein and mRNA expression, respectively. Results from both approaches converged to indicate that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields. Other prominent sites of mRNA and protein expression include subcortical limbic system structures (amygdala, bed nucleus of the stria terminalis), sensory relays associated with the auditory, olfactory, vestibular, and trigeminal systems, several raphe nuclei, and a number of cell groups in the brainstem reticular core. Expression in the hypothalamus appears largely limited to the ventral premammillary and dorsomedial nuclei; only isolated CRF-BP-stained cells are apparent in neurosecretory cell groups. Dual immunstaining for CRF and CRF-BP revealed a partial colocalization in some of these regions. In addition, prominent CRF-BP-stained terminal fields have been identified in association with CRF-expressing cell groups in circumscribed hypothalamic and limbic structures. In the anterior pituitary, CRF-BP mRNA and immunoreactivity were colocalized with corticotropin-immunoreactivity in a majority of corticotropes. Thus, CRF-BP could serve to modify the actions of CRF by intra-and intercellular mechanisms, in CRF-related pathways in the central nervous system and pituitary.