Objectives: POMC derived ACTH and αMSH exert anorectic actions within the VMN of the hypothalamus
via MC4- und MC3-R. Downstream, BDNF/Trk-B signalling is involved. The role of endogenous
ACTH is not yet clear. In this study, behavioral parameters and the expression of
MC4-R and BDNF were examined.
Methods: Exp 1: Effects of i.c.v. ACTH (9.3µg/rat) on BDNF and MC4-R expression in VMN were
studied in male adrenalectomized (ADX) or sham-operated rats (n=6) after 24h food
deprivation; saline served as control. Exp 2: Effects of endogenous ACTH on BDNF and
MC4-R expression in VMN were studied in satiated (food deprived for 24h, re-fed at
9 a.m.) and ad-libitum fed rats (n=5). At 7 p.m., peptide antibodies (Ab) were applied
into the PVN (2µg/rat; IgG, ACTH-Ab, αMSH-Ab, ACTH-Ab+αMSH-Ab). In both experiments,
chow and water were measured hourly; in the end, animals were weighed and decapitated;
expression studies were by in-situ hybridization.
Results: Exp 1: BDNF mRNA expression was upregulated by ACTH i.c.v. (sham: p=0.029, ADX: n.s.)
and decreased by ADX (saline: p=0.016, ACTH: p=0.001). In contrast, MC4-R mRNA expression
was decreased by ACTH i.c.v. (sham: p=0.001, ADX: p=0.091), ADX was without effect.
Food intake was decreased by ACTH injection (sham: p=0.004, ADX: p=0.014), ADX was
without effect. Exp 2: In satiated rats, BDNF mRNA was decreased (ACTH-Ab: p=0.027,
αMSH-Ab: p=0.031, ACTH-Ab+αMSH-Ab p=0.023) and MC4-R mRNA increased (ACTH-Ab: p=0.008,
αMSH-Ab: p=0.015, ACTH-Ab+αMSH-Ab p=0.027) by all Ab. Food intake differed between
IgG and all Ab groups (ACTH-Ab: p=0.005, αMSH-Ab: p=0.001, ACTH-Ab+αMSH-Ab p=0.001).
In contrast, Ab application in ad-libitum fed rats was without effect on mRNA expression
and food intake.
Discussion: The effects of ACTH on BDNF and MC4-R expression are independent of peripheral ACTH
actions. In satiated rats, with presumably high endogenous levels of POMC derived
peptides, Abs effectively block the actions of ACTH and αMSH on BDNF and MC4-R mRNA.
In contrast, Abs were ineffective in the condition of presumably low POMC expression.
