Exp Clin Endocrinol Diabetes 2007; 115 - P01_137
DOI: 10.1055/s-2007-972393

Role of hypothalamic ACTH and α-MSH in appetite regulation – an in situ hybridization study of BDNF and MC4-receptor mRNA expression

K Paulus 1, C Schulz 1, H Lehnert 2
  • 1Klinik für Endokrinologie, Magdeburg, Germany
  • 2Medical School, Coventry University Hospital, Warwick, United Kingdom

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.