Biosynthesis of polypeptide hormones

The biosynthesis of numerous polypeptide hormones implicates two types of precursors: pre- and prohormones. The structure, characteristics, and role of these hormone precursors is discussed taking as examples parathyroid hormone and insulin. After this general introduction, the case of the common precursor for adrenocorticotropin and beta-lipotropin is then discussed. Its maturation proceeds through a serie of proteolytic steps which lead to the formation of various end products characterized each by a biological activity of its own.     

Cellular action of gastrointestinal polypeptide hormones.

The present state of chemistry, structure-activity relationship and cellular mode of action of gastrointestinal polypeptide hormones (gastrin, secretin, cholecystokinin-pancreozymin, caerulein and bombesin) are reviewed. Possible structure of polypeptide receptors and the mechanism of peptide--receptor interaction are described, and the role of acetylcholine and histamine in secretion discussed. The present data support the hormonal-receptor significance of cyclic nucleotides (cAMP, cGMP) in the cellular regulation of secretion.     

Binding studies of polypeptide hormones to bovine neurophysins.

Experimental binding isotherms of [9-glycinamide-1-(14)C]oxytocin and [9-glycinamide-1-(14)C]arginine vasopressin to purified neurophysins I and II at pH = 4.4, 5.4, 6.5, 7.4, and 8.5 and 6 degrees, 22 degrees, and 37 degrees in aqueous buffers are reported. For purposes of comparison, binding isotherms for [4-glycine-1-(14)C]oxytocin to neurophysin II and I in aqueous buffer, and [9-glycinamide-1-(14)C]oxytocin to neurophysin II in dimethylsulfoxide under selected conditions are also reported. A brief discussion of the interpretation of binding isotherms is entered into and apparent binding constants are derived. The results indicate that the interpretations presented in the literature up to now are much too simple. There are, in contrast, multiple binding sites of oxytocin and vasopressin to the neurophysins and large temperature dependences of the number of sites and their binding constants. We find, in fact, that at 37 degrees the binding of neurohypophysial hormones to the supposed storage proteins is rather weak even at the pH of maximum binding.     

Localization of four polypeptide hormones in the saurian pancreas.

Glucagon, insulin, somatostatin, and pancreatic polypeptide have been localized in the anolian pancreas using peroxidase-antiperoxidase immunocytochemistry. The most abundant endocrine cell type contains glucagon. Insulin-containing cells are the next most numerous. Somatostatin-immunoreactive cells tend to be localized at the periphery of the islet cords. Pancreatic polypeptide-containing cells are a minor endocrine component scattered throughout the exocrine pancreas and occasionally within the islet areas. No staining was observed after application of antigastrin serum.     

Protein and polypeptide hormones as inhibitors

It is becoming increasingly apparent that hormones regulate morphogenetic processes and metabolic reactions through inhibitory mechanisms as well as stimulatory effects. Inhibition by protein and polypeptide hormones and the numerous analogs that have been prepared, was discussed in a recent article (1). The present brief review is concerned with more recent developments in this field, including the role of protein and polypeptide hormones in the control of cell proliferation and differentiation.     

Interaction of polypeptide hormones with lipid momolayers

1. The interaction between lipid monolayers spread on the surface of water and oxytocin, [8-arginine]-vasotocin and [1-asparagine-5-valine]-angiotensin II in the subphase was investigated in a Langmuir surface trough by studying the changes in pressure produced on injection of various quantities of the polypeptide solution under the film. 2. The effect of 2m- and 4m-urea on the character of the adsorption is reported. 3. Structures for the adsorbed films formed in this way are suggested. 4. If the lipid monolayer is taken as a suitable model of cell membranes, then it may be supposed that the effect of such structures forming in cell membranes would be to provide effective ;pores' to facilitate the movement of water and other small molecules across the membrane.     

Biosynthesis of the C-terminal amide in peptide hormones

Recent developments in the study of peptide amidation are reviewed. The main areas covered are assay procedures, purification of amidating enzymes, co-fact0rs and regulation; mechanism and specificity of the amidating reaction, and multiple forms of the amidating enzyme and glycosylation. Discussion is presented on aspects that are poorly understood and new areas open to investigation are indicated.     

Biosynthesis of precocenes-I and -II,anti-juvenile hormones

Administration of [2-¹⁴C]-sodium acetate and [2-¹⁴C]-mevalonic acid to Ageratum conyzoides plants has shown that the aromatic moiety of the precocenes is derived from acetate and the other five carbon atoms are of terpenoid origin.     

Biosynthesis of islet amyloid polypeptide. Elevated expression in mouse beta TC3 cells

Islet amyloid polypeptide (IAPP) messenger RNA levels, biosynthesis, processing, and secretion were studied in cultured mouse beta TC3 insulinoma cells. Northern blot analysis revealed that the size of IAPP mRNA (0.9 kb) in beta TC3 cells was the same as that in normal mouse islets; IAPP mRNA was approximately 60% of the level of insulin mRNA in beta TC3 cells. However, the ratio of synthesis of insulin to IAPP was approximately 6:1, suggesting that IAPP mRNA is not translated efficiently in these cells. Metabolic labeling of beta TC3 cells with [3H]leucine revealed the synthesis of both a precursor form of IAPP (pro-IAPP) of apparent Mr 7400 and a mature form (IAPP) of apparent Mr 3900. In pulse-chase experiments, pro-IAPP could be shown to be processed to IAPP in a manner similar to proinsulin. The t1/2 for conversion of pro-IAPP to IAPP was about 25 min, faster than the t1/2 for proinsulin to insulin of 70 min. A significant proportion of newly synthesized IAPP and insulin precursors were secreted via a constitutive pathway from beta TC3 cells. Possible effects of dexamethasone and forskolin on IAPP mRNA levels and biosynthesis were examined but no effects were observed. In conclusion, the IAPP gene is strongly expressed in beta TC3 cells leading to the biosynthesis, proteolytic processing, and secretion of IAPP, a putative islet hormone.     

Biosynthesis of human sialophorins and analysis of the polypeptide core

Biosynthesis was examined of sialophorin (formerly called gpL115) which is altered in the inherited immunodeficiency Wiskott-Aldrich syndrome. Sialophorin is greater than 50% carbohydrate, primarily O-linked units of sialic acid, galactose, and galactosamine. Pulse-labeling with [35S]methionine and chase incubation established that sialophorin is synthesized in CEM lymphoblastoid cells as an Mr 62,000 precursor which is converted within 45 min to mature glycosylated sialophorin, a long-lived molecule. Experiments with tunicamycin and endoglycosidase H demonstrated that sialophorin contains N-linked carbohydrate (approximately two units per molecule) and is therefore an N,O-glycoprotein. Pulse-labeling of tunicamycin-treated CEM cells together with immunoprecipitation provided the means to isolate the [35S]-methionine-labeled polypeptide core of sialophorin and determine its molecular weight (58,000). This datum allowed us to express the previously established composition on a "per molecule" basis and determine that sialophorin molecules contain approximately 520 amino acid residues and greater than or equal to 100 O-linked carbohydrate units. A recent study showed that various blood cells express sialophorin and that there are two molecular forms: lymphocyte/monocyte sialophorin and platelet/neutrophil sialophorin. Biosynthesis of the two forms was compared by using sialophorin of CEM cells and sialophorin of MOLT-4 cells (another lymphoblastoid line) as models for lymphocyte/monocyte sialophorin and platelet/neutrophil sialophorin, respectively. The time course of biosynthesis and the content of N units were found to be identical for the two sialophorin species. [35S]Methionine-labeled polypeptide cores of CEM sialophorin and MOLT sialophorin were isolated and compared by electrophoresis, isoelectrofocusing, and a newly developed peptide mapping technique.(ABSTRACT TRUNCATED AT 250 WORDS)