ACTH-Induced lipolysis in rat adipocytes: Structure-activity relationships

Abstract

The lipolytic action of natural porcine ACTH1(-39) and of a number of highly purified synthetic ACTH peptide fragments was studied using rat adipocytes. Of the analogues tested, only ACTH1(-24) exhibited full lipolytic activity with respect to intrinsic activity and affinity. Several shorter fragments appeared to be full agonists but had lower affinity. Fragments ACTH5(-10) and ACTH7(-10) were inactive. No antagonistic effects against the lipolytic action of ACTH could be demonstrated with substimulatory doses of ACTH1(-16), ACTH1(-10), ACTH7(-24) and ACTH11(-24). Based on the relative potency derived from dose-response curves, a more refined model with respect to the active centers being encoded in various sequences of the hormone, is proposed.

Reintoxication: the release of fat‐stored Δ9‐tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

“…This presumably occurred due to ACTH-induced lipolysis in vivo. Previous studies, as well as the current one, have shown that systemic administration of ACTH increases lipolysis, as gauged by increased plasma levels of glycerol ( Spirovski et al, 1975;Opmeer et al, 1978;Boston and Cone, 1996).…”

Molecular Identification of the Human Melanocortin-2 Receptor Responsible for Ligand Binding and Signaling

“…In early years, ACTH1-14, ACTH11-19 and ACTH11-24 were reported to increase corticosterone levels in the isolated adrenal cell system and ACTH11-24 plays an important role in adipocyte function (14,24,42,45). However, ACTH1-14 was also reported not able to bind MC2R (48).…”

“…Extensive studies have been performed to determine the molecular basis of the ACTH interaction with cognate melanocortin receptors (MCRs) in the last 2 decades, but inconsistent results have failed to produce a clear picture of mechanistic function. In early years, ACTH1-14, ACTH11-19, and ACTH11-24 were reported to increase corticosterone levels in the isolated adrenal cell system, with ACTH11-24 playing an important role in adipocyte function (14,24,42,45); however, ACTH1-14 was reportedly not able to bind MC2R (48). A potential explanation for these variations is that different methods of adrenal cell preparation were used and/or separate receptors may be involved in these peptide activities (53).…”

“…A potential explanation for these variations is that different methods of adrenal cell preparation were used and/or separate receptors may be involved in these peptide activities (53). Further studies using some ACTH peptide truncations indicated that ACTH1-17 is the minimal peptide required for ligand binding and signaling (14,24,42,45). However, detailed structure-function analysis of ACTH residues responsible for MC2R binding and signaling is still unclear.…”