Concomitant synthesis of beta-endorphin and alpha-melanotropin from two forms of pro-opiomelanocortin in the rat pars intermedia.

Abstract

In the pars intermedia of rat pituitary glands, two forms of a common precursor for corticotropin (ACTH) and fl-lipotropin with apparent molecular weights of 34,000 and 36,000 were resolved by sodium dodecyI sulfate/acrylamide gradient slab gel electrophoresis. Hi -prformance liquid chromatographic analysis of [asS~methionine-labeled tryptic fragments of the two forms of the precursor revealed that both contained copies of ACTH-1-8) and fl-lipotropin4(61-69) sequences. When biosynthetic studies were performed in the presence of tunicamycin, the 34,000-and 36,000-dalton forms were replaced by a peptide with an apparent molecular weight of 32,000. It was therefore concluded that the 34,000-and 36,000-dalton forms of the precursor represent two glycoprotein variants of similar polypeptides, differing in the number of asparagine-linked carbohydrate moieties. During pulse-chase incubations with , the precursor forms were cleaved into two major groups of labeled products: (i) ,-endorphin and (ii) a mixture of ACTH fragments closely related to a-melanotropin. No ACTH-(1-39) was found at the end of a 2-hr chase period, suggesting that ACTH is not a significant hormone product of the rat pars intermedia.

Immunocytochemical Localization and Biochemical Characterization of α‐Melanocyte‐Stimulating Hormon in the Brain of the Rainbow Trout, Salmo gairdneri

“…Post-translational processing of POMC in pituitary cells has the potential to yield a number of biologically active peptides including ACTH, melanocyte-stimulating hormone (MSH) and fi-endorphin (4)(5)(6). Proteolytic cleavage of POMC is a tissue specific process which largely depends on the profile of enzymes present within the secretory granules.…”

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

“…Several investigators have shown that more than one form of pro-opiomelanocortin may occur in the same species, and even in the same tissue [3,5,. From studies with mouse pituitary tumor cells [lo] and rat pars intermedia [3], it was concluded that these multiple forms differ mainly in the extent of glycosylation. More recently, two observations were published which suggest that proopiomelanocortins with different primary structures may be synthesized.…”

“…In the pars intermedia this prohormone is processed to peptides related to a-melanotropin, corticotropin and endorphin [3 -61. Several investigators have shown that more than one form of pro-opiomelanocortin may occur in the same species, and even in the same tissue [3,5,. From studies with mouse pituitary tumor cells [lo] and rat pars intermedia [3], it was concluded that these multiple forms differ mainly in the extent of glycosylation.…”

Action of proteolytic enzymes on lipotropins and endorphins: Biosynthesis, biotransformation and fate

“…However, in the intermediate lobe of the pituitary, in brain and presumably also in placenta and pancreas, main products are fl-endorphin and v-lipotropin, c~-melanotropin, corticotropin-like intermediate lobe peptide (CLIP) and several shorter NH 2 terminal pro-opiomelanocortin fragments ( Fig. 1) Eipper, 1978a,b, 1979;Roberts et aL, 1978;Crine et al, 1978Crine et al, , 1979Eipper and Mains, 1981;Liotta et al, 1981;. These peptides all arise during a discrete proteolytic cleavage mechanism which is directed by paired basic amino acids.…”