Characterization and localization of an immunoreactive growth hormone-releasing hormone precursor form in normal and tumoral human anterior pituitaries.
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.
Rauch
C
C
INSERM U-223, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Li
J Y
JY
Croissandeau
G
G
Berthet
M
M
Peillon
F
F
Pagesy
P
P
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D011498:Protein Precursors; D012333:RNA, Messenger; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone