The possibility has been mentioned that a change in the structure is responsible for the deviant behavioral activity of
gamma-endorphin in extracts of postmortem brain and pituitary gland samples of schizophrenic patients. This paper describes the investigation of this possibility by means of:
amino acid composition analysis of alpha- and
gamma-endorphin isolated from a pituitary gland of a schizophrenic patient; and nucleotide sequence analysis of the
gamma-endorphin coding region of
pro-opiomelanocortin (
POMC)
mRNA from two other pituitary glands, using the primer extension method. Both methods require no more than a single pituitary to obtain reliable results. alpha- and
gamma-endorphin were isolated from an
acid extract by gel filtration and two subsequent HPLC steps. In addition, the
gamma-endorphin region of
beta-endorphin was analyzed by enzymatic cleavage of
beta-endorphin and isolation of the resulting fragment. Single-stranded
gamma-endorphin cDNA was synthesized by
reverse transcriptase using total cellular pituitary
RNA and a 5' 32P-labeled
oligodeoxyribonucleotide primer (20-mer) hybridizing close to the
gamma-endorphin coding region of
POMC mRNA. Single-stranded
cDNA was digested with restriction
enzyme HaeIII which generated a 148
nucleotides long radioactive
cDNA fragment containing the
gamma-endorphin cDNA sequence. The sequence of the 148
nucleotides fragment was determined. Neither the
amino acid composition analysis nor the amino acid sequence derived from the
cDNA nucleotide sequence revealed differences between schizophrenics and controls. Thus, no evidence was found for changes in the amino acid sequence of pituitary
gamma-endorphin in these analyses, which include 3 cases of
schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)