Maturation of the hypothalamo‐neurohypophysial system

Heller, H.; Lederis, K.

doi:10.1113/jphysiol.1959.sp006244

Cited by 95 publications

(38 citation statements)

References 28 publications

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“…As pointed out in an earlier report (12), in newborn animals the secretion of ADH is small when compared to adults. Under our experimental conditions, the endogenous ADH levels might have been too small to stimulate the medullary cAMP formation at a sufficient rate.…”

Section: Discussionmentioning

confidence: 76%

Studies on the Immaturity of the ADH-Dependent cAMP System in Conscious Newborn Piglets—Possible Impairing Effects of Renal Prostaglandins

1981

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SummaryIn 24 conscious newborn piglets the effects of 20 &kg body weight IV 1-deamino-&~-arginine-vasopressin (DDAVP) in group 1, 5 mg/kg P O indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate. urinary osmolality, creatinine clearance, total urinary and nephrogenols cyclic-adknosine 3':s'-monophosphate (CAMP) excretion. medullary cAMP content. and renal prostaglandin (PG)E2 and PGF2,, excreiion. DDAVP alone had no-signifilcant effects on the above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly Recent in vivo studies provided evidence that the restricted urinary concentrating capacity of the neonatal kidney results from the inability of the medullary cyclic adenosine 3':5'-monophosphate (CAMP) system to accumulate cAMP sufficiently in the presence of antidiuretic hormone (ADH) (14) in addition to the reduced glomerular filtration rate (2). the structural immaturity of the loop of Henle (5), and the low excretion rate of urea (7). Some observations indicate that the unresponsiveness of the cAMP system to ADH may result not only from a functional immaturity of the medullary adenylate cyclase (20,22), but additionally from the interference of renal prostaglandins (PGs) of the E-series with the hydro-osmotic action of ADH. This view is based on the following observations: (1) in isolated collecting ducts, the effect of ADH on the water permeability was blunted when PGEl was applied (10); (2) conversely, in adult mammals when PG synthesis was inhibited the effect of ADH on water reabsorption was increased (1, 3. 8. 17).High concentrations of PGs were found in urine of fetal lambs (23). and high PGEl levels were inversely correlated with urinary cAMP excretion in premature infants (15). If a relatively high PGE? formation in the kidney of neonates is indeed a restrictive parameter for renal medullary cAMP accumulation, it should be possible to increase the effect of ADH on urinary concentration by inhibiting PG synthesis.Therefore. we measured urinary concentration in newborn piglets, both before and after the administration of either DDAVP or indomethacin alone and after administration of DDAVP plus indomethacin. The studies were performed in conscious animals because it has been shown that in the unanaesthetized animal indomethacin does not change renal blood flow (24), whereas administration of this drug in the anaesthetized dog is associated with a marked fall in renal blood flow (16). MATERIALS A N D METHODS EXPERIMENTALStudies were carried out on 24 male conscious piglets (strain. Deutsche Landrasse) within the first 24 hr after birth. The animals weighed between 1000 and 1700 g and had free access to suck. The following protocol was used.Control Period. In all animals used. first all urine in the bladder was removed by puncturing the bladder suprapubically. Then the urethra was closed by glue and plaster, and each ...

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Section: Discussionmentioning

confidence: 76%

Studies on the Immaturity of the ADH-Dependent cAMP System in Conscious Newborn Piglets—Possible Impairing Effects of Renal Prostaglandins

1981

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“…Pharmacological potencies were determined by rat uterus (Heller & Lederis, 1959) and rat pressor (Dekanski, 1952) (Gisin, 1973) and were subsequently acetylated (Stewart & Young, 1969 Deprotection and purification of peptides. After completion of the required cycle procedure, the dry peptide-resin was ammonolysed in 150ml of methanol saturated with NH3 (at 0°C) for 2 days in a sealed flask at room temperature (23°C).…”

Section: Methodsmentioning

confidence: 99%

Influence of the peptide-chain length on disulphide-bond formation in neurohypophysial hormones and analogues

Moore¹

1978

Biochemical Journal

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[8-Arginine]vasopressin, [8-arginine]vasotocin, oxytocin and oxypressin, the 'ring' derivatives pressinamide and tocinamide, and the extended-chain analogues Pro-Arg-Val- [8-arginine]vasopressin and [8-arginine]vasopressinoyl-Ala-Met-Ala-NH2, were synthesized by the solid-phase method and purified by sequential gel filtration on Sephadex G-15 in 50% acetic acid and 0.2M-acetic acid. Controlled oxidation of the thiol groups of the reduced peptides obtained after deprotection with sodium in liquid ammonia gave rise to products that depended on the length of the peptide chain: (i) nonapeptides gave monomer and dimer species, (ii) hexapeptides produced mixtures containing higher polymers, and (iii) dodecapeptides gave predominantly monomer with some dimerized material. The evidence suggests that the presence of the acyclic tail tripeptide in the nonapeptide hormones induces a conformation in the preceding hexapeptide that favours the formation of an intramolecular disulphide bond. For [8-argininelvasopressin, intramolecular disulphide-bond formation is enhanced by extension of the peptide chain from either the N-or the C-terminus. The possible significance of these studies to neurohypophysial hormone-prohormone relationships is discussed.The formation of an intramolecular disulphide bond occurs at some stage during the biosynthesis of the neurohypophysial hormones, and presumably takes place in an environment that ensures intramolecular alignment of the thiol groups so that intermolecular disulphide bonds are not formed. During the chemical synthesis of neurohypophysial hormones, both intra-and inter-molecular disulphidebond formation are observed after oxidation of the reduced peptides, suggesting that the hormones Abbreviations used: abbreviations for amino acids and protecting groups are those recommended by the IUPAC-ILJB Commission on Biochemical Nomenclature (1972); Boc, t-butyloxycarbonyl. Synthetic analogues of neurohypophysial hormones: themselves do not represent an 'efficient' environment for intramolecular disulphide-bond formation. The possibility exists that these hormones are biosynthesized in the form of prohormones, which, when released from the ribosomes, are conformationally predisposed to spontaneous and efficient intramolecular disulphide-bond formation.An index of the precyclic conformation of a given neurohypophysial-hormone analogue may be obtained by determining the degree of difficulty with which its intramolecular disulphide bond is formed, as reflected in the ratio of monomer to polymer(s) obtained after controlled.oxidation of the reduced peptide. By using the appropriate analogues, this approach can give information on the relative [Arg8]vasopressinoyl-Ala-Met-Ala-NH2, Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-Ala-Met-Ala-NH2-Vol. 173

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“…This homology would have been clear to Lederis, given his doctoral work on the ultrastructure of the mammalian neurohypophysis (Heller and Lederis, 1959;Lederis, 1963) and his work on the isolation of the neurohypophyseal hormone storage granules (Barer et al, 1963). In view of the expected parallels between the mammalian and teleost neurosecretory systems under discussion at the time, there is no doubt that Karl Lederis's insight during his Bristol Pub discussions with Howard Bern led to his sabbatical in the Bern laboratory in Berkeley, working with the collected Gillichthys mirabilis urophyseal tissues that were available there.…”

Section: Overviewmentioning

confidence: 99%

“…All of these approaches were ongoing in the Heller laboratory in terms of the study of the storage and secretion of oxytocin and vasopressin from the posterior pituitary (Heller and Lederis, 1959;Barer et al, 1963). Thus, the paradigm for hormone discovery to be used for the Urotensins had already been clearly established for the identification of the vasoactive-hypertensive, galactogogic, oxytocic and antidiuretic principles present in extracts of the posterior pituitary gland, as begun by Oliver and Schäfer (1895).…”

Section: Principles For the Isolation Of Neuropeptides: Oxytocin And mentioning

confidence: 99%

Urotensin I–CRF–Urocortins: A mermaid’s tail

Pittman¹,

Hollenberg²

2009

General and Comparative Endocrinology

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From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I-CRF-Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI-CRF-Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a 'classical' pharmacological approach to generate new insights about the UI-CRF-Urocortin hormone family.

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Maturation of the hypothalamo‐neurohypophysial system

Cited by 95 publications

References 28 publications

Studies on the Immaturity of the ADH-Dependent cAMP System in Conscious Newborn Piglets—Possible Impairing Effects of Renal Prostaglandins

Studies on the Immaturity of the ADH-Dependent cAMP System in Conscious Newborn Piglets—Possible Impairing Effects of Renal Prostaglandins

Influence of the peptide-chain length on disulphide-bond formation in neurohypophysial hormones and analogues

Urotensin I–CRF–Urocortins: A mermaid’s tail

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