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WO1996029002A1 - Methode de diagnostic de carences en hormone de croissance hypophysaire - Google Patents

Methode de diagnostic de carences en hormone de croissance hypophysaire Download PDF

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Publication number
WO1996029002A1
WO1996029002A1 PCT/US1996/003607 US9603607W WO9629002A1 WO 1996029002 A1 WO1996029002 A1 WO 1996029002A1 US 9603607 W US9603607 W US 9603607W WO 9629002 A1 WO9629002 A1 WO 9629002A1
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WO
WIPO (PCT)
Prior art keywords
trp
growth hormone
ghrp
phe
ghrh
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1996/003607
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English (en)
Inventor
Barry B. Bercu
Richard F. Walker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of South Florida
University of South Florida St Petersburg
Original Assignee
University of South Florida
University of South Florida St Petersburg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of South Florida, University of South Florida St Petersburg filed Critical University of South Florida
Priority to EP96908837A priority Critical patent/EP0871392A4/fr
Publication of WO1996029002A1 publication Critical patent/WO1996029002A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/575—Hormones
    • G01N2333/61—Growth hormones [GH] (Somatotropin)

Definitions

  • GH growth hormone
  • a diagnostic protocol and kit for evaluating pituitary growth hormone (GH) secretory capability as a means to identify the etiology of GH deficiency in children and adults includes measuring GH secretion, as determined by changes in serum, plasma, or whole blood GH concentrations following administration of the xenobiotic GH releasing hexapeptide (GHRP-6) or any of its peptidyl or non-peptidyl synthetic analogues that release GH by the same cellular mechanism as GHRP-6 (the group/family of compounds are referred to as GHRX) .
  • GHRP-6 xenobiotic GH releasing hexapeptide
  • GHRX group/family of compounds
  • FIGURE 1 is a diagram of the three step provocative testing of the present invention.
  • FIGURE 2 is a dose response curve for GHRP-6 in rats pretreated with vehicle (triangles) , ⁇ r-methyl-p- tyrosine (circles) , or GHRH antiserum (squares) . Values represent means ⁇ SEM (8 rats per dose and treatment) in plasma collected 15 minutes after administration of GHRP- 6.
  • GHRH has been identified as a naturally occurring GH secretagogue, an endogenous analogue of a group referred to as GH releasing compound (GHRC) .
  • GHRP-6 represents a synthetic analogue of another, yet unidentified, endogenous GH secretagogue.
  • the relationship between GHRP-6 and its endogenous counterpart is presumably analogous to that of morphine and the endorphins.
  • GHRP-6 and analogues thereof means GHRP-6 and any peptide or nonpeptide compound that releases GH by the same cellular mechanism.
  • analogue Dorland ' s Illustra ted Medical Dictionary, 25th Edition, W.B. Saunders, Philadelphia, PA., p. 78
  • analogue in the present invention is used to refer to functional and metabolic analogues that are peptides or nonpeptides that cause the release of GH by the same cellular mechanism as GHRP-6, i.e., they are compounds of similar activity.
  • a nonpeptide functional or metabolic analogue of GHRP-6 has been disclosed by Smith et al . (1993) that acts through the same site as GHRP-6.
  • the compound, L-692,429 is antagonized by the same agents as is GHRP-6 and interacted with GRF.
  • This and related compounds activate the same cellular receptors and second messengers as GHRP- 6 in the course of initiating its relevant action (e.g. growth hormone release) . All of these analogues and compounds of similar activity are useful in practicing the present invention as described herein; however, these peptides and nonpeptides should not be considered as being exhaustive of the GHRP-6 analogue-compounds useful in practicing the present invention.
  • GHRH-efficacy has been reported to be reduced 50 to 75% in old rats (Sonntag et al . , 1983) ; therefore, applicants tested the effect of GHRP-6 alone and in combination with GHRH on GH release in old rats. Peak plasma GH concentrations resulting from GHRP-6 administration in old rats were approximately 60% less than in young rats. In contrast, peak plasma GH concentrations were greater in old rats than in young rats administered GHRP-6 and GHRH. Since target organs sometimes become hyperresponsive when tonic and/or phasic stimulation decreases, than one would expect exaggerated responses to provocative exogenous stimuli under experimental conditions.
  • GHRP-6 activity was significantly attenuated in young female rats administered GHRH antiserum or ⁇ -methyl-p-tyrosine to reduce endogenous GHRH concentrations.
  • GHRH antiserum or ⁇ -methyl-p-tyrosine was significantly attenuated in young female rats administered GHRH antiserum or ⁇ -methyl-p-tyrosine to reduce endogenous GHRH concentrations.
  • naturally occurring decrements in endogenous GHRH during aging contributed to the blunted response to GHRP-6 that applicants observed (Walker et al . , 1991) .
  • GHRH activity is also dependent upon a yet unidentified endogenous co-secretagogue whose concentrations decline during aging, then applicants' data support the hypothesis that extrinsic pituitary deficits contribute, at least in part, to attenuated GH secretory responses to administered GHRH.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Endocrinology (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Genetics & Genomics (AREA)
  • Physiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention porte sur un protocole de diagnostic et un matériel d'évaluation des capacités sécrétoires de l'hormone de croissance hypophysaire (GH) en tant que moyen d'identification de l'étiologie des carences en GH chez l'enfant et chez l'adulte. Ledit protocole consiste à mesurer la sécrétion de GH par mesure des variations de la concentration en GH du sérum, du plasma ou du sang entier suite à l'administration de GHPRP-6 (hexapeptide de libération de GH) xénobiotique, ou de l'un de ses analogues de synthèse, du genre peptidyle ou non peptidyle, libérant la GH par le même mécanisme cellulaire que le GHPRP-6. Le composé de libération (GHRC) du GH naturel ou ses analogues sont également administrés à des enfants ou des adultes atteints de troubles liés à une carence en GH, puis la sécrétion de GH est mesurée. Après avoir évalué les effets d'une administration indépendante de secrétagogues du GH sur les variations de la concentration sanguine de GH, on peut mesurer les effets d'une administration conjointe de différents secrétagogues de GH sur la concentration sanguine de GH chez l'enfant et chez l'adulte.
PCT/US1996/003607 1995-03-17 1996-03-14 Methode de diagnostic de carences en hormone de croissance hypophysaire Ceased WO1996029002A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP96908837A EP0871392A4 (fr) 1995-03-17 1996-03-14 Methode de diagnostic de carences en hormone de croissance hypophysaire

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US40584295A 1995-03-17 1995-03-17
US08/405,842 1995-03-17

Publications (1)

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WO1996029002A1 true WO1996029002A1 (fr) 1996-09-26

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PCT/US1996/003607 Ceased WO1996029002A1 (fr) 1995-03-17 1996-03-14 Methode de diagnostic de carences en hormone de croissance hypophysaire

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EP (1) EP0871392A4 (fr)
WO (1) WO1996029002A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007093820A1 (fr) 2006-02-18 2007-08-23 Ardana Bioscience Limited Méthodes et kits permettant de diagnostiquer une carence en hormone de croissance

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5246920A (en) * 1992-06-15 1993-09-21 University Of South Florida Treatment of hyperprolactinemia
WO1994000759A1 (fr) * 1992-06-29 1994-01-06 University Of South Florida Procedure de diagnostic permettant d'evaluer l'etiologie de l'insuffisance staturale

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5246920A (en) * 1992-06-15 1993-09-21 University Of South Florida Treatment of hyperprolactinemia
WO1994000759A1 (fr) * 1992-06-29 1994-01-06 University Of South Florida Procedure de diagnostic permettant d'evaluer l'etiologie de l'insuffisance staturale

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
BOWERS C Y, ALSTER D K, FRENTZ J M: "THE GROWTH HORMONE-RELEASING ACTIVITY OF A SYNTHETIC HEXAPEPTIDE INNORMAL MEN AND SHORT STATURED CHILDREN AFTER ORAL ADMINISTRATION", JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, THE ENDOCRINE SOCIETY, US, vol. 74, no. 02, 1 January 1992 (1992-01-01), US, pages 292 - 298, XP001052748, ISSN: 0021-972X, DOI: 10.1210/jc.74.2.292 *
BOWERS C Y, ET AL.: "GROWTH HORMONE (GH)-RELEASING PEPTIDE STIMULATES GH RELEASE IN NORMAL MEN AND ACTS SYNERGISTICALLY WITH GH-RELEASING HORMONE", JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, THE ENDOCRINE SOCIETY, US, vol. 70, no. 04, 1 January 1990 (1990-01-01), US, pages 975 - 982, XP001052749, ISSN: 0021-972X *
BOWERS C. Y., ET AL.: "STRUCTURE-ACTIVITY RELATIONSHIPS OF A SYNTHETIC PENTAPEPTIDE THAT SPECIFICALLY RELEASES GROWTH HORMONE IN VITRO.", ENDOCRINOLOGY, THE ENDOCRINE SOCIETY, US, vol. 106., no. 03., 1 March 1980 (1980-03-01), US, pages 663 - 667., XP000607438, ISSN: 0013-7227 *
BUTENANDT O: "DIAGNOSTIC VALUE OF GROWTH HORMONE-RELEASING HORMONE TESTS IN SHORTCHILDREN", ACTA PAEDIATRICA SCANDINAVICA, WILEY, ALMQVIST OCH WIKSELL, STOCKHOLM, SE, vol. 349, 1 January 1989 (1989-01-01), ALMQVIST OCH WIKSELL, STOCKHOLM, SE, pages 93 - 99, XP001052743, ISSN: 0001-656X *
CHENG K, ET AL.: "THE SYNERGISTIC EFFECTS OF HIS-D-TRP-ALA-TRP-D-PHE-LYS-NH2 ON GROWTH HORMONE (GH)-RELEASING FACTOR-STIMULATED GH RELEASE AND INTRACELLULAR ADENOSINE 3',5'-MONOPHOSPHATE ACCUMULATION IN RAT PRIMARY PITUITARY CELL CULTURE", ENDOCRINOLOGY, THE ENDOCRINE SOCIETY, US, vol. 124, no. 06, 1 January 1989 (1989-01-01), US, pages 2791 - 2798, XP001052744, ISSN: 0013-7227 *
CORDIDO F, ET AL.: "MASSIVE GROWTH HORMONE (GH) DISCHARGE IN OBESE SUBJECTS AFTER THE COMBINED ADMINISTRATION OF GH-RELEASING HORMONE AND GHRP-6: EVIDENCE FOR A MARKED SOMATOTROPH SECRETORY CAPABILITY IN OBESITY", JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, THE ENDOCRINE SOCIETY, US, vol. 76, no. 04, 1 January 1993 (1993-01-01), US, pages 819 - 823, XP001052747, ISSN: 0021-972X, DOI: 10.1210/jc.76.4.819 *
GERTZ B J, ET AL.: "GROWTH HORMONE RESPONSE IN MAN TO L-692,429, A NOVEL NONPEPTIDE MIMIC OF GROWTH HORMONE-RELEASING PEPTIDE-6", JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, THE ENDOCRINE SOCIETY, US, vol. 77, no. 05, 1 January 1993 (1993-01-01), US, pages 1393 - 1397, XP001052751, ISSN: 0021-972X, DOI: 10.1210/jc.77.5.1393 *
MOMANY F A, ET AL.: "CONFORMATIONAL ENERGY STUDIES AND IN VITRO AND IN VIVO ACTIVITY DATA ON GROWTH HORMONE-RELEASING PEPTIDES", ENDOCRINOLOGY, THE ENDOCRINE SOCIETY, US, vol. 114, no. 05, 1 January 1984 (1984-01-01), US, pages 1531 - 1536, XP001052745, ISSN: 0013-7227 *
MOMANY F A, ET AL.: "DESIGN, SYNTHESIS, AND BIOLOGICAL ACTIVITY OF PEPTIDES WHICH RELEASE GROWTH HORMONE IN VITRO", ENDOCRINOLOGY, THE ENDOCRINE SOCIETY, US, vol. 108, no. 01, 1 January 1981 (1981-01-01), US, pages 31 - 39, XP001052746, ISSN: 0013-7227 *
ROBINSON B M, ET AL.: "ACUTE GROWTH HORMONE (GH) RESPONSE TO GH-RELEASING HEXAPEPTIDE IN HUMANS IS INDEPENDENT OF ENDOGENOUS GH-RELEASING HORMONE", JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, THE ENDOCRINE SOCIETY, US, vol. 75, no. 04, 1 January 1992 (1992-01-01), US, pages 1121 - 1124, XP001052750, ISSN: 0021-972X, DOI: 10.1210/jc.75.4.1121 *
See also references of EP0871392A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007093820A1 (fr) 2006-02-18 2007-08-23 Ardana Bioscience Limited Méthodes et kits permettant de diagnostiquer une carence en hormone de croissance
JP2009526989A (ja) * 2006-02-18 2009-07-23 アーダナ バイオサイエンス リミテッド 方法及びキット
JP4852728B2 (ja) * 2006-02-18 2012-01-11 エテルナ ツェンタリス ゲーエムベーハー 方法及びキット
US8192719B2 (en) 2006-02-18 2012-06-05 Aeterna Zentaris Gmbh Methods and kits to diagnose growth hormone deficiency by oral administration of EP 1572 or EP 1573 compounds

Also Published As

Publication number Publication date
EP0871392A4 (fr) 2001-08-29
EP0871392A1 (fr) 1998-10-21

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