Journal of Neuroscience, Vol 8, 3967-3977, Copyright © 1988 by Society for Neuroscience
Differential biosynthesis and posttranslational processing of vasopressin and oxytocin in rat brain during embryonic and postnatal development
M Altstein and H Gainer
Laboratory of Neurochemistry, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
The biosynthesis and posttranslational processing of arginine vasopressin
(AVP) and oxytocin (OT) peptides in the developing rat brain and pituitary
were studied using antibodies and complementary separation methods that
permitted a quantitative radioimmunoassay (RIA) analysis of precursor,
intermediate, and completely processed forms of the peptides. Precursor
forms of the peptides were first detected in rat brain as early as
embryonic day (E) 15 for AVP and E17 for OT. Proteolytic cleavage products
of the precursors were detected 1 d later for both peptides. AVP was
present in a fully processed (amidated) from immediately (E16) and
throughout fetal development. OT was cleaved from its precursor starting on
E18 but remained in an intermediate (C- terminal extended) form until E21,
when amidated OT was first detected in the pituitary. Hence, Pro-AVP
processing in the fetus was immediate and complete, whereas Pro-OT
processing in the fetus was much slower and incomplete, resulting in the
generation of partially processed, nonamidated stable forms of the peptide
(OT-Gly10, OT-Gly10-Lys11, and OT-Gly10-Lys11-Arg12). The presence of
OT-Gly10-Lys11-Arg12 as a major, stable intermediate form, indicated that
the in vivo pattern of endoproteolytic cleavage occurred principally at the
C-terminus of the pair of basic amino acids at the tripeptide spacer
sequence (Gly-Lys- Arg) in the precursor. Although both precursors were
first expressed nearly simultaneously in the brain, the steady-state levels
of the precursors were very different throughout fetal life. From E16-E21,
the quantities of AVP precursors and peptides were 5- to 10-fold greater
than those of OT, suggesting a much higher level of precursor biosynthesis
in the AVP neurons. In addition to these differences in the regulation of
biosynthesis and processing, AVP peptides were axonally transported to the
pituitary 3 d earlier than OT peptides, and in far greater (20-fold)
abundance. The early presence and abundance of amidated AVP in the brain
and pituitary suggests a trophic function for this peptide during
development.
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