γ‐MSH Peptides in the Pituitary

Abstract

The melanocortin (MC) gamma3-MSH is believed to signal through the MC3 receptor. We showed that it induces a sustained increase in intracellular free calcium levels ([Ca(2+)](i)) in a subpopulation of pituitary cells. Most of the cells responding to gamma3-MSH express more than one pituitary hormone mRNA. The effect of gamma3-MSH is blocked by SHU9119, a MC3R and MC4R antagonist, in only 50% of the responsive cells, suggesting that in half of these cells the mediating receptor is not the MC3R. Low picomolar doses of gamma3-MSH increase [Ca(2+)](i) in the growth hormone (GH)- and prolactin (PRL)-secreting GH3 cell line. gamma2-MSH and alpha-MSH display a similar effect. SHU9119 does not affect the gamma3-MSH-induced [Ca(2+)](i) response. MTII, a potent synthetic agonist of the MC3R, MC4R, and MC5R, also shows no or low potency in increasing [Ca(2+)](i). By means of RT-PCR, the mRNA of the MC2R, MC3R, and MC4R receptors is undetectable. Experiments testing gamma2-MSH analogues with single alanine replacements show that, unlike the classic MCRs, the His(5)-Phe(6)-Arg(7)-Trp(8) sequence in gamma2-MSH is not a core sequence for activating the gamma-MSH receptor in GH3 cells, whereas Met(3) is essential. Low nanomolar doses of gamma-MSH increase intracellular cAMP levels. Blockade of protein kinase A abolishes the [Ca(2+)](i) responses to gamma3-MSH. gamma2-MSH increases binding of [S(35)]GTPgammaS to membrane preparations of GH3 cells. The pharmacological characteristics of gamma-MSH peptides and analogues on [Ca(2+)](i) and the signal-transduction pathways present strong evidence for the expression of a hitherto uncharacterized gamma-MSH receptor in GH3 cells, belonging to the G protein-coupled receptor family.

Characterization of two Pro-opiomelanocortin gene variants and their effects on carcass traits in beef cattle

“…In mammals the 5' end of the γ-MSH sequence is highly conserved but the 3' end is not. This lack of conservation is thought to be why the short forms of γ-MSH are still active in mice and rats [10,11]. While the 3' location of the deletion in γ-MSH likely does not affect its bioactivity, there may be a gene processing failure based on its proximity to the dibasic amino acids KR (Figure 1).…”

Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin

“…An alanine scanning of γ 2 -MSH indicated the importance of Met 3 , His 5 , Phe 6 , Arg 7 , and Trp 8 for functional activity at the human MC3-5R, similar to residues in α-MSH that are important for activity [ 59 ]. γ-MSH is expressed in the pituitary and arcuate nucleus, as well as adrenal medulla [ 72 , 73 , 74 , 75 ]. Differences in receptor selectivity have been observed between species, where γ 2 -MSH is selective for the human MC3R over MC4R and MC5R, whereas there is no selectivity between the mouse MC3R and MC5R [ 59 , 76 , 77 ].…”

Role of α-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation

“…The earliest known function of a-MSH was its ability to stimulate melanogenesis in melanocytes in the skin and therefore to increase pigmentation [69]. Later on, the cloning of five different melanocortin receptors allowed new research on the effects of a-MSH revealing its influence on energy homeostasis [17,54], stimulation of exocrine gland secretion [19], stimulation of erection [83], regulation of sexual behavior [118] and endocrine glands [27,66], and regulation of the cardiovascular system [53].…”