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Table 2 The distribution of three forms α-MSH in brain tissues by Mass spectrometry analysis
Male
Female
des- mono-act di-act des- mono-act di-act
Hypothalamus + + — + + +
Anterior pituitary + + — — + +
Arcuate nucleus + — — + + —
Neurointermediate lobe + + + + + +
Median eminence + + — + + +
Cerebral cortex + + — + + +
Pre-optic area + + + + + +
Spinal cord — — — — — —
Brain stem — — — — — —
Cerebellum — — — — — —
Discussion
Some researches indicated that no authentic α-MSH was detected in extracts of rat brain regions
or human pituitary. In these tissues the only α-MSH variant detected was characterized as des-acetyl
α-MSH. Conversely, acetylated α-MSH was found to be the predominant form in rat pituitary(12). It is
the same result of female sheep in our research, Only acetylated forms(including mono-act and di-act)
were detected, but except acetylated α-MSH ,we can still find des-acetyl α-MSH in male sheep.
The role of the N-acetyl group has been extensively studied in conjunction with
melanocortinergic regulation of food intake. Peripheral injection of α-MSH in viable yellow obese
mice resulted in significantly lower food intake and body weight gain than in mice injected with the
same doses of desacetyl-α-MSH (17). Tsujii and Bray (16) injected acetyl-α-MSH and des-acetyl-α-
MSH intracerebroventricularly (i.c.v.) into food-deprived rats and found that acetyl-α-MSH produced
a highly significant reduction of food intake at doses of 100 and 250 pmol whereas des-acetyl-α-MSH
had no effect at any dose between 100 and 2500 pmol. Similarly, after i.c.v. administration to fasted
rats, doses of 1, 3, or 6 nmol acetyl-α-MSH resulted in decreased food intake (18). Des-acetyl-α-MSH
did not produce a significant effect at these doses but reduced food intake at a dose of 25 nmol. The
most recent demonstration of differential effects of MSH acetylation on the regulation of food intake
has been provided by Guo et al.2004(19), who again demonstrated that i.c.v. injection of 3 nmol
acetyl-α-MSH, but not des-acetyl-α-MSH, resulted in inhibition of food intake in rats.
Differential effects of acetylated and non-acetylated α-MSH have also been noted in the
adrenal cortex, adipose tissue, and bone. In addition to ACTH or melanocortin-2 receptors
(MC2R),MC3R and MC5R are expressed in the adrenal cortex (20,21).Both acetyl-α-MSH
and des-acetyl-a-MSH stimulate aldosterone, corticosterone, and cortisol secretion from
human adrenocortical cells in vitro (22). Des-acetyl-α-MSH is much more potent than acetylα-MSH,
but both are far less effective than ACTH (1–24). ACTH (1–24) elicited significant
secretion of all three steroids at doses of 1.0 pmol whereas the threshold dose was 1.0 nmol
for des-acetyl-α-MSH and 100 nmol for acetyl-α-MSH. The relative potencies of ACTH and
α-MSH agree with the 104-fold difference in potency between the two peptides in rat adrenal
(23). However, others have failed to find any evidence for steroidogenic activity or MC2R
binding of α-MSH in rat or mouse adrenal (24,25). Des-acetyl-, di-acetyl- and mono-acetyl-α-
MSH have been demonstrated to have lipolytic activity in rabbits both in vivo and in vitro,
but none of the forms is effective in rats (24). The threshold dose of des-acetyl-α-MSH to
increase plasma free fatty acid (FFA) concentration in rabbits was 1 mg/kg, but for the two
acetylated forms was 0.33 mg/kg. As determined by peak levels of FFA, the relative potencies
of diacetyl-/monoacetyl-/desacetyl-α-MSH were 8.3/5.3/1. The effects of the three peptides
on lipolytic activity in rabbit adipose tissue slices followed similar patterns except that the
threshold doses and potencies of acetyl-α-MSH and di-acetyl-α-MSH were equivalent. MC2R,
MC4R, and MC5R have now all been identified in adipose tissue by quantitative reverse
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