Zusammenfassung
Versuche mit natürlichem, aus Schweinehypophysen gewonnenem und synthetischem, aus 23 bzw. 24 Aminosäuren bestehendem adrenocorticotropen Hormon (ACTH) führten zu folgenden Ergebnissen:
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1.
An Ratten verursachte natürliches und synthetisches ACTH einen dosisabhängigen Anstieg der unveresterten Fettsäuren (UFS) im Plasma. Bei subcutaner Injektion waren 1,5 I E/kg natürliches ACTH etwa so wirksam wie 0,1–0,2mg/kg Noradrenalin. Adrenalektomie hatte keinen Einfluß auf diese Wirkung. Am isolierten, epididymalen Fettgewebe von Ratten war synthetisches ACTH 2–3 mal schwächer lipolytisch wirksam als natürliches ACTH. Bruchstücke des synthetischen ACTH, die keine corticotrope Wirkung hatten, waren auch lipolytisch unwirksam. Das Nonapeptid Bradykinin und das Decapeptid Kallidin hatten ebenfalls keine lipolytische Wirkung.
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2.
Änderungen des Noradrenalingehaltes im Fettgewebe durch Vorbehandlung der Tiere mit Monoaminoxydase-Hemmstoffen bzw. mit Reserpin und Analogen hatte keinen Einfluß auf die lipolytische Wirkung des ACTH; Vorbehandlung mit Trijodthyronin verstärkte die lipolytische ACTH-Wirkung in vivo und in vitro.
Auf molarer Basis ist die lipolytische Wirkung des ACTH stärker als diejenige des Noradrenalins, wird aber nicht durch Noradrenalin vermittelt und ist auch unabhängig von der corticotropen Wirkung des Hormons; sie ist eine direkte Wirkung des Polypeptides auf das Fettgewebe.
Summary
The lipolytic activities of natural porcine adrenocorticotropic hormone (ACTH) and of synthetic peptides containing the N-terminal 23 and 24 amino acids of ACTH resp. were studied in rats.
In vivo, both procine and synthetic ACTH elicited a dose dependent increase of plasma free fatty acids (FFA), reaching peak values within 10–20 min after subcutaneous injection, whereas the plasma corticosteronelevelincreased more slowly and reached maximal values 30–60 min after the s. c. injection. The lipolytic response to 1,5 IU/kg of porcine ACTH was comparable to that of 0,1–0,2mg/kg of norepinephrine. The molar ratio in the lipolytic potency of ACTH and norepinephrine obtained in vivo was approximately 200. On a molar base, synthetic ACTH (24 amino acids) was approximately 5 times less potent than porcine ACTH in increasing plasma FFA. The lipolytic response to ACTH was unchanged in acutely adrenalectomized rats.
Experiments in vitro confirm those in vivo: upon incubation with epididymal adipose tissue of rats synthetic ACTH (23 amino acids) was 2–3 times less potent in promoting lipolysis than porcine ACTH, while norepinephrine was only 10 times less potent than the latter. Synthetic peptides corresponding to the amino acid sequences 1–5, 5–10 and 11–24 of natural ACTH with had no adrenocorticotropic actions were also without effect on lipolysis in vitro. Similarly, the polypeptides bradykinin and kallidin had no FFA-mobilizing actions.
In view of previous reports that the lipolytic action of ACTH is mediated by norepinephrine, the lipolytic action of ACTH was studied after alteration of the norepinephrine content of adipose tissue: pretreatment of rats with reserpine or syrosingopine which almost completely depleted adipose tissue norepinephrine failed to alter the lipolytic response to ACTH in vivo and in vitro. On the other hand, tyramine which acts through the liberation of endogenous norepinephrine was inffective in these animals. Pretreatment with monoamine oxidase inhibitors which raised the norepinephrine content of adipose tissue by more than 50% had also no influence on the lipolytic effect of ACTH but potentiated that of metaraminol which predominantly acts like tyramine. It is concluded that the lipolytic action of ACTH is not mediated by adipose tissue norepinephrine.
This is not in contrast with the finding that pretreatment with triiodothyronine potentiates the lipolytic effects of both ACTH and norepinephrine in vito and in vitro since these hormones may stimulate the lipolytic system through the same mechanism.
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Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft (We 272). Über einen Teil der Ergebnisse wurde auf der 5. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft berichtet (Stock u. Westermann 1964).
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Stock, K., Westermann, E. Über die lipolytische Wirkung von natürlichem und synthetischem adrenocorticotropem Hormon (ACTH). Naunyn - Schmiedebergs Arch 251, 488–502 (1965). https://doi.org/10.1007/BF00246135
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DOI: https://doi.org/10.1007/BF00246135