A peptide has been isolated from ovine hypothalamus which, at 1 x 10(-9)M, inhibits secretion in vitro of immunoreactive rat or human growth hormones and is similarly active in vivo in rats. Its structure is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH The synthetic replicate is biologically active.

https://science.sciencemag.org/content/sci/179/4068/77.full.pdf

Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone

SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was first isolated from ovine hypothalamic extracts on the basis of its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-glucagon-growth hormone releasing factor-secretin superfamily. The sequence of PACAP has been remarkably well conserved during the evolution from protochordate to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide whose activity remains unknown. Two types of PACAP binding sites have been characterized. Type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes, the PACAP-specific PAC1 receptor, which is coupled to several transduction systems, and the two PACAP/VIP-indifferent VPAC1 and VPAC2 receptors, which are primarily coupled to adenylyl cyclase. PAC1 receptors are particularly abundant in the brain and pituitary and adrenal glands whereas VPAC receptors are expressed mainly in the lung, liver, and testis. The wide distribution of PACAP and PACAP receptors has led to an explosion of studies aimed at determining the pharmacological effects and biological functions of the peptide. This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions

It is a privilege to be able to contribute to this volume in which Professor Zervas’ friends, students, and colleagues have joined together to honor him and his remarkable contributions to peptide chemistry. Although I did not know him until after his days in the Bergmann Laboratory at the Rockefeller Institute, I can claim the distinction of now working in those very same rooms that they occupied back in the mid-1930s. Like all peptide chemists, I am greatly indebted to Professor Zervas, having depended so heavily on the carbobenzoxy group and on the various modified urethan protecting groups which have been direct extensions of the revolutionary advance that Bergmann and Zervas made.

Solid-phase peptide synthesis.

The molecular structures of several polypeptides isolated from hypothalamic tissue have been established and the synthesis of these compounds has been achieved. These polypeptides selectively stimulate or inhibit the release of anterior pituitary hormones and melanocyte-stimulating hormone. Various studies indicate their important physiological role and support the concept that some of these polypeptides are hormones. Some synthetic hypothalamic hormones and their derivatives may find important clinical and veterinary applications.

http://science.sciencemag.org/content/sci/179/4071/341.full.pdf

Hypothalamic Regulatory Hormones

[Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence].

Synthetic luteinizing hormone-releasing factor analogs. Series of short-chain amide LRF homologs converging to the amino terminus.

Four analogs of ovine somatostatin (SRIF, PSOMATOTROPIN RELEASE INhibiting factor), the sequence of which is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-trp-Lys-Thr-Phe-Thr-Ser-Cys-OH, have been synthesized by the solid-phase methodology. The compounds were assayed and were found to possess the following somatotropin release inhibiting potencies relative to pure synthetic somatostatin in vitro and in vivo, respectively: [Ala3,14]somatostatin, 0.6 and 2.0%; [SMe-Cys3,14]somatostatin, 4 and 0.6%; [NAc-Cys3]somatostatin, 39 and 105%; [des-Ala1-Gly2]somatostatin, 65 and 71%. The dihydrosomatostatin analogs [NAc-Cys3-H2]somatostatin and [des-Ala1Gly2-H2]somatostatin after two purifications by gel filtration were assessed to be at least 80% homogeneous and had respectively 99 and 89% of somatostatin potencied in vivo. Structure-activity relationships are discussed.

Guillemin R

Papers

[Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence].

Synthetic luteinizing hormone-releasing factor analogs. Series of short-chain amide LRF homologs converging to the amino terminus.

Somatostatin analogs. Relative importance of the disulfide bridge and of the Ala-Gly side chain for biological activity.

Molecular structure of the hypothalamic factor (LRF) of ovine origin monitoring the secretion of pituitary gonadotropic hormone of luteinization (LH)

Control of Anterior Pituitary Hormone Secretion