Immunohistochemical evidence that growth hormone-releasing factor (GRF) neurons contain an amidated peptide derived from cleavage of the carboxyl-terminal end of the GRF precursor.
Antisera were raised against synthetic replicates of the carboxyl-terminal (C-terminal) fragment of the precursor to human GH-releasing factor (GRF) (pre-proGRF) whose structure was predicted from the complementary DNA cloned from a pancreatic tumor. These antisera were used along with antisera to human GRF itself to search for the presence of related molecules in the human hypothalamus, with an immunohistochemical approach. The antisera to pre-proGRF that recognize specifically the C-terminal amidated form of pre-proGRF stain GRF neurons in their cell bodies, fibers, and nerve endings that are in contact with portal capillaries of the median eminence. Antisera against the nonamidated form of the molecule did not give any staining in the hypothalamus. These results strongly suggest that human hypothalamic GRF derives from a precursor immunologically related (and probably identical) to the tumorous one and that this precursor is cleaved inside GRF cell bodies to give, in addition to the GRF-44-NH2 a second amidated peptide, the C-terminal pre-proGRF that is transported distally to nerve endings and most probably coreleased with GRF into portal capillaries.
Bloch
B
B
Baird
A
A
Ling
N
N
Guillemin
R
R
D000328:Adult; D000577:Amides; D005455:Fluorescent Antibody Technique; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007031:Hypothalamus / Q000032:analysis* / Q000196:embryology; D007124:Immunoenzyme Techniques; D009474:Neurons / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis* / Q000378:metabolism
D000577:Amides; D010446:Peptide Fragments; D011498:Protein Precursors; C047524:pre-pro-growth hormone releasing factor; D013007:Growth Hormone-Releasing Hormone