Ciba Foundation Symposium 172 - Corticotropin-Releasing

Engaged on Corticotropin-Releasing think about numerous platforms, specialists current a coherent depiction of this peptide's function within the regulate and coordination of the reaction to stress-inducing events.


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Wittert Division of Endocrinology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA Abstract. An understanding of how second messengers and their ligands are coupled to CRF gene activation is necessary if we are to understand the regulation of the CRF gene in physiological and pathological states. The protein kinase A, protein kinase C and glucocorticoid second messenger systems mediate most of the regulation of the CRF gene. In in vifrosystems, CRF gene expression is stimulated 20-30-fold by activation of either the protein kinase A or the protein kinase C system.

Vaughan, 70th Annual Meeting Endocrine Society 1988, abstr) had first demonstrated CRF expression in this line. Treatment with TPA increases CRF mRNA content in NPLC cells more than 30-fold, and is associated with an increase of about 100 nucleotides in the length of the polyadenylate tail of CRF mRNA (Rosen et a1 1992, Adler et al 1992). The peak effect of TPA on CRF mRNA levels, which occurred 24 h after drug exposure, is later than that observed for most TPA-responsive genes. This, together with the fact that the effect of TPA on CRF mRNA content requires on-going protein synthesis (Rosen et a1 1992), suggests that the continued synthesis of a labile protein is required, and possibly that activation of CRF gene expression by components of the PKC pathway occurs via initial activation of another gene.

TATA and CAAT sequences are located 30 and 32 Majzoub et al FIG. 1. Regulation of expression of the CRF (CRH) gene by forskolin (FSK) in cultured human trophoblasts. Trophoblasts from term placenta were prepared and cultured for 16-88 h in the presence (+) or absence (-) of FSK and harvested for extraction of total RNA at the indicated times (hours). An equal amount of a sense strand CRF complementary (c) RNA (std) was added to each sample before extraction of RNA, to serve as a recovery standard.

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