1. Interactions of adrenocorticotropic hormone with its adrenal receptors. Degradation of ACTH-1-24 and ACTH-11-24
J M Saez, A Dazord, P Bataille, A M Morera J Biol Chem . 1975 Mar 10;250(5):1683-9.
Crude membranes (20,000 times g pellet) prepared from human, rat, and ovine adrenals bind 125-I-corticotropin-(1-24)-tetracosapeptide (125-I-ACTH-1-24) and degrade unbound hormone. The degradation is dependent on temperature and the concentration of membrane proteins. The degradation of 125-I-[9-tryptophan(o-nitrophenylsulfenyl)]-corticotropin-(1-24)-tetracosapeptide (125-I-NPS-ACTH-1-24) is similar to 125-I-ACTH-1-24, but that of 125-I-corticotropin-(11-24)-tetradecapeptide (125-I-ACTH-1-24 is inhibited by ACTH-1-24 and corticotropin-(1-10)-decapeptide (ACTH-1-10), but ACTH-11-24 at the same molar concentration has no effect. On the other hand, the degradation of 125-I-ACTH-11-24 is protected by ACTH-11-24 and ACTH-1-24, but not by ACTH-1-10. This suggests two systems of degradation, one will have the NH-2-terminal sequence of ACTH-1-24 as substrate, and the other the 11-24 COOH-terminal sequence. The main label product from the degradation of the 125-I-ACTH-1-24 and 125-I-ACTH-11-24 behaves as [125-I]monoiodotyrosine on Sephadex G-50 and paper chromatography. The independence of ACTH binding to its receptor and degradation is demonstrated by the following facts. (a) Calcium and pancreatic trypsin inhibitor completely inhibit the binding at concentrations when the degradation is not altered; (b) the sequences of peptides of ACTH which inhibit the binding and degradation of 125-I-ACTH-1-24 are different.
2. Effects of ACTH-(11-24) on the corticosteroid production of isolated adrenocortical cells
K S Szalay, D De Wied, E Stark J Steroid Biochem . 1989 Feb;32(2):259-62. doi: 10.1016/0022-4731(89)90261-6.
The steroidogenic action of ACTH-(11-24) was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(11-24) stimulated the corticosterone production of zona fasciculata cells and the aldosterone production of zona glomerulosa cells; in addition, it potentiated the effects of ACTH-(1-39) on both cell systems. It is suggested that the ACTH molecule contains more active sites for steroidogenesis than usually acknowledged, as has been found for lipolysis and behavior.
3. [Structural and functional organization of ACTH: synthesis and properties of analogs of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexa-amino acids instead of a natural sequence of ACTH 19-24 amino acids]
I A Vosekalna, P Ia Romanovskiĭ, A A Skuin'sh, M P Ratkevich, I V Syskov Bioorg Khim . 1984 May;10(5):618-25.
To assess the role of amino acid sequence ACTH 19-24 in the corticotropin structure and steroidogenic activity, the analogues of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexaglycine, hexaphenylalanine, hexaglutamic acid or hexalysine instead of the natural 19-24 sequence have been synthesized by conventional methods. All these compounds in water have the CD curves characteristic of random coil, CD spectra of analogue ACTH-(1-24)-tetracosapeptide and hexalysine-containing analogue ACTH-(11-24)-tetradecapeptide in trifluoroethanol indicate the presence of alpha-helices. The latter compound manifested higher steroidogenic activity than ACTH-(11-24)-tetradecapeptide. All the other analogues were either less active than ACTH-(1-24)-tetracosapeptide or inactive over the concentration range 10(-5)-10(2) mg/ml, thereby testifying to functional importance of the 19-24 sequence for manifesting full steroidogenic activity.
