The hypothalamic melanocortin 4 receptor, its endogenous agonist, alpha melanocyte stimulating hormone and the endogenous antagonist, Agouti related peptide (Agrp) regulate energy homeostasis. However, the physiological role of the hypothalamic melanocortin receptor, MC3-R and its agonist, gamma MSH are currently unknown. We have previously shown that the MC3/4 agonist, a-MSH has no effect on GnRH release from hypothalamic explants and does not influence plasma gonadotrophins following third ventricle injection. In this study we demonstrate that activation of MC3-R modulates the hypothalamo-pituitary gonadal axis.
Gamma MSH stimulated intracellular cAMP accumulation and GnRH secretion in a dose-dependent manner, in the immortalised GnRH clonal cell lines, GT1-7 and NLT. Agrp blocked this action. RT-PCR demonstrated the presence of MC3-R mRNA in GT1-7 cells. Gamma MSH stimulated GnRH release from medial basal hypothalamic explants in a dose dependent manner. Injection of the MC3/4 agonist, a-MSH, into the medial preoptic area significantly increased 1 hour food intake but was without significant effect on plasma gonadotrophins. However, following injection of g-MSH into the medial preoptic area, at a dose that did not influence food intake, there was a significant increase in plasma gonadotrophins.
We have demonstrated MC3-R activation to significantly increase GnRH release from clonal cell lines and hypothalamic explants and to stimulate plasma LH in vivo. This suggests that MC3-R may play a role in the control of the hypothalamo-pituitary gonadal axis
08 - 11 Apr 2002
British Endocrine Societies