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Endocrinology, Vol 136, 2594-2601, Copyright © 1995 by Endocrine Society
ARTICLES |
C Rauch, JY Li, G Croissandeau, M Berthet, F Peillon and P Pagesy
INSERM U-223, Faculte de Medecine Pitie-Salpetriere, Paris, France.
Arguments favor an in situ synthesis of GH-releasing hormone (GHRH) in the normal and tumoral human anterior pituitary. These tissues may express human (h) GHRH messenger RNA, contain hGHRH-(1-44)-NH2, and secrete in vitro an immunoreactive form (ir-form) of the peptide. Here, we characterize and localize the precursor of hGHRH in human anterior pituitary tissues using RIAs specific for the C-terminus or the midportion of hGHRH-(1-44)-NH2, size-exclusion chromatography, HPLC, Western blotting, and immunocytochemistry. The anterior pituitary ir- forms were compared to those found in hypothalamus, posterior pituitary, and GHRH-secreting endocrine pancreatic tumors. Three ir- forms of hGHRH with mol wt of 30-45, and 5 kilodaltons (kDa) were detected. The 30- to 45-kDa ir-form was very likely to consist of hGHRH bound to proteins. The 5-kDa ir-form represented mature forms of hGHRH. It was the major form in tissues actively synthesizing and/or secreting hGHRH. Nontumoral anterior pituitaries contained significant amounts of mature hGHRH. The 10-kDa form was identified as a hGHRH precursor ir- form. In addition to its expected presence in the hypothalamus and GHRH- secreting tumors, normal and tumoral human anterior pituitaries contained an identical ir-form of the hGHRH precursor. Cells immunoreactive for the hGHRH precursor were observed in pituitary adenomas. Evidence for precursor and mature ir-forms of hGHRH in anterior pituitary tissues provides conclusive arguments for the endogenous synthesis of the neuropeptide.
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