From β-lipotropin to β-endorphin and 'pro-opio-melanocortin'

Abstract

Studies on the biosynthesis of beta-LPH on the one hand, and of ACTH on the other, have produced a new concept, that of a single precursor form which contains three active molecules. Thus, it is proper to name such a precursor 'pro-opio-melanocortin.' The concept that beta-LPH was a precursor molecule was first put forward in 1967 and was based on both structural forms and biological activities. The discovery that morphine-like substances are part of the C-terminal fragment of beta-LPH brought an additional important biological side product. That, together with the recent demonstration of ACTH as part of a still larger precursor, constitutes an exciting model for the study of peptide hormone biosynthesis. We have shown unambiguously that beta-endorphin is the result of a maturation process from the large precursor, while beta-LPH is an important and transient intermediary. Since it is also present in the brain, our recent results using pars intermedia cells can be applied to study the fabrication and degradation of these molecules in the brain. We expect to see it established that all other neuropeptides are also biosynthesized as larger precursor molecules whose structure at the site of cleavage could well be constituted of two basic amino acids like in the pro-opio-melanocortin.

In vitro biosynthesis and processing of composite common precursors containing amino acid sequences identified immunologically as neurophysin I/oxytocin and as neurophysin II/arginine vassopressin

“…These composite precursors bear a close resemblance to viral polyproteins [7] which also comprise several distinct functional products. To date, direct evidence for such cellular polyproteins [8], in the form of amino acid sequence, is only available for pro-opiocortin [ 1,9] which consists of corticotropin, /3-lipotropin, endorphins and melanotropins. However, indirect evidence points to the existence of similar composite precursors in the hypothalamus, namely the common precursors to arginine vasopressin/neurophysin II and oxytocin/ neurophysin I.…”

Biosynthesis of Two Structurally Different Pro‐opiomelanocortins in the Pars Intermedia of the Amphibian Pituitary Gland

“…The maps showed that the primary structures of the two forms of pro-opiomelanocortin differ in at least two parts of the molecules, one part concerning the endorphin region Extensive biosynthetic investigations with a mouse adrenocorticotropic tumor cell line have provided evidence for the existence of a common precursor to corticotropin and /3-lipotropin [l]. Studies concerning the pars intermedia of the pituitary gland revealed the occurrence in this tissue of a similar prohormone, which was named pro-opiomelanocortin [2]. In the pars intermedia this prohormone is processed to peptides related to a-melanotropin, corticotropin and endorphin [3 -61.…”

“…Studies concerning the pars intermedia of the pituitary gland revealed the occurrence in this tissue of a similar prohormone, which was named pro-opiomelanocortin [2]. In the pars intermedia this prohormone is processed to peptides related to a-melanotropin, corticotropin and endorphin [3 -61.…”

Biosynthesis of a γ3‐Melanotropin‐like Peptide in the Pars Intermedia of the Amphibian Pituitary Gland

“…In the pars intermedia the same prohormone functions as the precursor for a-melanotropin, corticotropinlike intermediate lobe peptide [corticotropin-(I 8 -39)], and /I-endorphin ; it was, therefore, named pro-opiomelanocortin [2]. Nakanishi et al [3] revealed the nucleotide sequence of the cloned cDNA, which is complementary to the mRNA that codes for pro-opiomelanocortin in bovine pituitary glands.…”