Endocrine Abstracts

Melanocortin receptors (MC_S, 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 displaying a multitude of actions however their role in reproductive physiology is unclear. Previously, we have shown a reduction of pituitary hormone content and abnormalities in testes morphology in male MC₃ null mice. The aim of this study was to characterise MC_S expression in the male mouse reproductive axis and to investigate the effects of MC_S agonists/antagonists on in vitro testicular testosterone production (TP).

MC_S expression patterns were determined in mRNAs from hypothalami, pituitaries and testes of Balb/c and C57BL/6 male mice by two-step reverse transcriptase (RT) - quantitative (q) PCR and analysed using qBase^plus. To examine the functions of MC_S in gonads, testes of Balb/c and C57BL/6 mice were hemi-sected and incubated with the potent MC₃ and, to a lesser extent, MC₄ agonist ([D-TRP⁸]-γ₂-MSH; 0.3–10 μg/ml) in the presence or absence of hCG (50 mIU/ml) and/or a MC₃/MC₄ antagonist and MC₁/MC₅ agonist (SHU9119; 10 μg/ml) for 5 h at 35 °C in air.

There were no significant differences in the pattern of MC_S expression between C57BL/6 and Balb/c. The most abundant MC in the hypothalamus and pituitary appears to be MC₃ whilst in the testis it was MC₂. TP in C57BL/6 mice is 50% less than in Balb/c: confirming published data that the former mice are hypoandrogenic. Activation of MC₃ and MC₄ using [D-TRP⁸]-γ₂-MSH had no or inhibitory effects on basal TP in Balb/c and C57BL/6, respectively. The same ligand decreased TP in both strains in the presence of hCG. In contrast, SHU9119±hCG increased TP threefold compared to basal levels independently of ligand dose in Balb/c. This study suggests that activation of specific MC_S can alter TP however further work is required.