The hypothalamic-pituitary-adrenal (HPA) axis is the major stress response system. Several components of the HPA axis, such as corticotropin-releasing hormone (CRH) and POMC peptides and their receptors are also present in the skin. In earlier studies, we showed that CRH inhibits cellular proliferation of immortalized human keratinocytes. We now examine further the functional activity of the HPA axis in the skin, by characterizing the actions of CRH on normal foreskin keratinocytes. The CRH receptor was detected as CRH-R1 antigen at 47 kDa in the cultured keratinocytes by Western blotting, and immunohistochemistry demonstrated its presence in the epidermal and follicular keratinocytes. CRH is also biologically active in cultured keratinocytes, where it inhibits proliferation and enhances the interferon-gamma-stimulated expression of the hCAM and ICAM-1 adhesion molecules and of the HLA-DR antigen. These effects were concentration-dependent, with maximal activity at CRH 10(-7) M. Thus, in the keratinocyte, the most important cellular component of the epidermis, CRH appears to induce a shift in energy metabolism away from proliferation activity, and toward the enhancement of immunoactivity. Therefore, similar to its central actions, cutaneous CRH may also he involved in the stress response, but at a highly localized level.
We evaluated the TSH secretory pattern and free T4 in 10 prepubertal children with short stature, normal response to GH provocative tests, and reduced GH integrated concentration (IC-GH) (GH neurosecretory dysfunction). Although their nadir TSH, peak TSH, TSH surge, and free T4 were lower than those of 12 children with short stature and normal IC-GH, none of the differences reached statistical significance. Thus, our results suggest that children with low IC-GH (GH neurosecretory dysfunction) exhibit a TSH secretory pattern and thyroid function similar to those with normal IC-GH.
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