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The pituitary neurointermediate lobe of genetically obese (ob/ob) mice contains a hormone which stimulates insulin release and which cross-reacts with a -COOH-terminal ACTH antiserum, suggesting that it is related to corticotropin-like intermediate lobe peptide (CLIP), the 18-39 fragment of ACTH. The hormone, which we have called beta-cell-tropin, has been shown to be present in the plasma of the ob/ob mouse and to potentiate glucose induced insulin secretion. We have now shown that ACTH22-39 prepared by tryptic digestion of human synthetic CLIP behaves similarly on Biogel chromatography and on reverse-phase HPLC to the naturally occurring beta-cell-tropin. Furthermore, beta-cell-tropin and ACTH22-39 have indistinguishable antigenic and insulin releasing properties.

Adipokinetic hormone, isolated from locust corpora cardiaca, has been identified as a blocked peptide: PCA-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2. The detailed structure is based on mass spectrometric data, substantiated in part by dansyl-Edman and carboxypeptidase data on thermolytic fragments. This is the first peptide hormone from an insect neuroendocrine organ to be fully characterised.

The rat calcitonin gene has recently been shown to encode a novel peptide (rat calcitonin gene-related peptide, rCGRP) thought to be produced in nervous tissue after tissue-specific RNA processing. This peptide has so far been identified only in rat tissue, by immunocytochemistry and immunoassay. We now report the isolation of a related (89% homology) peptide from human tissue (hCGRP) which we have sequenced using a novel mass spectrometric approach, fast atom bombardment (FAB) mapping. The human peptide differs significantly from the predicted rCGRP structure in four positions in the amino acid sequence (three effecting charge changes), and the presence of a disulphide bridge and an amide, surmised in the rat work, is proven in the hCGRP molecule. hCGRP was present in plasma from 10 patients with medullary thyroid carcinoma (MTC) and in 6 MTC tumours removed at surgery, suggesting the tissue distribution may differ from that in the rat where the peptide is reported to be absent from thyroid tissue. hCGRP is shown to have biological activity and it is possible that its presence in MTC plasma may be responsible for some of the symptoms in this disease.

Mass spectometry, conventionally used with smallish molecules (less than 1,000 daltons), has suprisingly emerged as a powerful technique for the determination of the amino acid sequences of proteins and the structure of glycopeptides as well as for the characterization of biologically active materials of unusual structure such as the peptidolipids. Further applications to biomedical problems are foreseen.

The secretion of aldosterone from the zona glomerulosa of the mammalian adrenal cortex is stimulated by ACTH, potassium, angiotensin II and III, growth hormone, serotonin and E series prostaglandins. Some experimental and clinical studies suggest that additional stimulants of the zona glomerulosa must exist, possibly including pituitary factors other than ACTH. The possibility that posterior pituitary extracts may contain a zona glomerulosa stimulant was first suggested 20 years ago, but has since received little attention. We describe here the purification from posterior pituitary extracts of activities that stimulate rat glomerulosa cells and whole tissue in vitro. One of the active compounds has been identified as alpha-MSH (melanocyte stimulating hormone).

Morphogens are signal molecules presumed to exist in embryos and to be involved in establishing the spatial pattern of cells during development. Differentiation inducing factor (DIF) has the properties of a morphogen required for producing the prestalk/prespore pattern in the aggregate formed by cells of the slime mould Dictyostelium in response to starvation. DIF-1, the major bioactive species after purification, has now been identified using a combined microchemical, spectroscopic and synthetic approach. The structure is defined as 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone, and represents a new class of effector molecule. The availability of relatively large quantities of synthetic and isotopically labelled materials should now allow progress towards a detailed understanding of the pattern-forming processes in Dictyostelium development.