Characterization of MC3 and the other melancortin receptors (MC) in the hypothalamo-pituitary-gonadal system of the mouse
Melanocortin receptors (MC, MC1–MC5) are GPCRs, activated with different affinities by the melanocortin peptides (α-, β-, γ-MSH and ACTH). MC3 has well characterised roles in both the central regulation of energy metabolism and peripheral inflammatory responses. The functions and distribution of MC3 and the other MC in tissues of the reproductive system are unclear. Compared to wild type mice (WT), an apparent decrease in fertility of MC3 null mice (MC3-/-) has been observed and hence it was the aim of this series of studies to characterize MC3 and the other MC in tissues of the mouse hypothalamo-pituitary-gonadal (HPG) system. The relative mRNA expressions of the MC have been identified at each level of the HPG axes in both male and female mice. It appeared that the MC mRNA expression may be regulated by the reproductive state of an animal and may change with age. Two different forms of POMC mRNA have been confirmed in the reproductive axes of both genders implicating local melanocortin production. Localization of MC3 protein was unsuccessful due to a lack of specificity of all the antibodies applied. Ablation of MC3 led to a decrease in the total pituitary hormone content in both male and female mice. The histology of testes of MC3-/- mice at different ages were abnormal compared to WT. In vitro incubation of hemi-sected testes of Balb/c or C57BL/6 mice in varying concentrations of selective MC3 agonist had modulatory, although non-significant, effects on testosterone production. However, MC3 activation during an inflammatory-like state in the testis, inhibited nitrite production but had no effects on the release of cytokines. The inhibitory action of MC3 agonist on nitrite release was also apparent in the K9 Leydig cell line, which expresses all five isoforms of MC. MC3 may be both directly and/or indirectly implicated in the control of the mouse HPG system. The anti-inflammatory action of testicular MC3 activation could lead to possible clinical applications of MC3 agonists in the treatment of inflammatory situations associated with the loss of fertility.
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