Post-translational processing of pro-opiomelanocortin (POMC)-derived peptides during fetal monkey pituitary development. I. Adrenocorticotropin (ACTH) and alpha-melanotropins (alpha-MSHs).
We have studied the post-translational processing of POMC-derived peptides during fetal monkey development using immunoassay and reverse-phase high-performance liquid chromatography (RP HPLC). Pituitary tissues obtained from fetal monkeys ranging from Gestational Day 50 to 155 were fractionated and analyzed for ACTH- and alpha-MSH-related peptides and compared to adult forms. Extracts of whole pituitary from Fetal Days 50 and 55 contained ACTH(1-39) and very small amounts of CLIP (corticotropin-like intermediate-lobe peptide; ACTH(18-39))-like immunoactivity. Acetylated alpha-MSHs were not detectable at Day 50. alpha-MSHs were barely detectable at Day 55. By Day 65, when pituitary lobes were separable, small amounts of des-, mono-, and diacetyl alpha-MSH were detectable in NIL extracts, but not in anterior lobe extracts. ACTH(1-39) levels were negligible when compared to increasing alpha-MSHs through Fetal Day 80 to 155 in the intermediate lobe. The CLIP immunoactivity was negligible in Day 80 and adult anterior lobe extracts. Thus, lobe-specific proteolytic processing of ACTH-related peptides was well established by midterm gestation. Marked increases of alpha-N- and alpha-N,O-acetylated forms of alpha-MSHs were detected during middle and late stage fetal development. Diacetyl alpha-MSH was the predominant form of alpha-MSH in adult NIL extracts. No acetylated alpha-MSHs were found in anterior lobe tissues, thus adult anterior lobe extracts contained almost exclusively ACTH(1-39). However adult NIL extracts contained two distinct forms of CLIP-related immunoactivity. Therefore changes in post-translational processing patterns of ACTH-related and alpha-MSH-related peptides continued to some extent, postnatally. These data indicate that marked changes in post-translational processing of POMC-derived ACTH-related products occur during the first half of monkey gestation.
Allen
R G
RG
Department of Biochemistry, Oregon Health Sciences University, Portland 97201.
Hatfield
J M
JM
Stack
J
J
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D053497:Corticotropin-Like Intermediate Lobe Peptide; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007118:Immunoassay; D008253:Macaca mulatta; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010902:Pituitary Gland / Q000196:embryology* / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000196:embryology / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D000521:alpha-MSH / Q000378:metabolism*
D010446:Peptide Fragments; D053497:Corticotropin-Like Intermediate Lobe Peptide; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone