Induction of melanocortin receptor (MC2-R & MC5-R) expression during adipocyte differentiation in the 3T3-L1 cell line and distribution of expression in mature adipose tissues

B. A. Boston, R. D. Cone

Research output: Contribution to journalArticle

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Abstract

It has been known for many years that adipocytes express high affinity ACTH and α-MSH binding sites, and that ACTH, α-MSH and β-LPH are potent lipolytic hormones. We show here that the adipocyte response to the melanocortin peptides results from the expression of both the ACTH (MC2) receptor as well as the newly discovered MC5 receptor. Using RTPCR and northern blot hybridization, high levels of ACTH receptor mRNA were found in all adipose tissues examined in the mouse, while MC5-R mRNA was found in a subset of these. Both receptor mRNAs were also found in the 3T3-L1 cell line, but only after the cells had been induced to differentiate into adipocytes. This cell line was then used to characterize the pharmacological properties of the MC2 and MC5 receptor sites in situ. The MC2 (ACTH) receptor exhibits properties similar to the ACTH receptor characterized in adrenocortical cells, coupling to activation of adenylyl cyclase with an EC50 of approximately 1nM. An MSH binding site characterized in these cells is presumably the MC5-R, due to the observation that this is the only other melanocortin receptor mRNA detected in these cells. Interestingly, this site displays a novel pharmacological property. The cloned MC5-R activates adenylyl cyclase equally well in response to ACTH, α-MSH and the synthetic α-MSH analogue NDP-α-MSH when transfected into heterologous cell systems. The synthetic analogue NDP-α-MSH, however, appears to be apotent antagonist of the MC5-R in 3T3-L1 adipocytes.

Original languageEnglish (US)
Pages (from-to)103A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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