Melanocortin receptors (MCs: MC1–MC5) are GPCRs, activated with different affinities by the melanocortin peptides (α-, β-, γ-MSH and ACTH). They are widely distributed throughout the body and have a multitude of actions. MC3 signalling has been reported to be involved in lactotroph development and prolactin release, however its functions, direct or indirect, in the other pituitary cells are not well understood. Previously, we have shown that there is a significant reduction in total pituitary hormone content in MC3 null mice (MC3-/-) and that this effect is more profound in males. The aim of this study was to characterise MCs expression in the hypothalamo-pituitary-gonadal systems of wild type (WT) and MC3-/- mice. MC expression patterns were determined in mRNAs from hypothalami, pituitaries and the gonads of 8 and 14 week old WT and MC3-/- male mice as well as WT females in different reproductive states by two-step reverse transcriptase (RT)-quantitative (q) PCR and analysed using qBaseplus. Comparisons between tissues showed that MC3, MC4 and MC5 are highly expressed in the hypothalami of 8 week old WT C57BL/6 mice compared with testes, with the pituitary having intermediate levels of MC3 and MC5 but low MC4 expression. MC2 mRNA expression is higher in testes than hypothalami but undetectable in the pituitary at this age. Surprisingly, in the absence of MC3, there was reduction in the relative mRNA expression of the other four MC in hypothalami and pituitaries but not in the testes. Preliminary data suggests that the pattern of MC expression in the hypothalamus and pituitary changes in older (14 week old) male animals and in females at different stages of pregnancy and lactation. This study demonstrates that a complex interaction between the different MCs may exist and that physiological status as well as age alters the pattern of specific receptor expression.