Journal
ENDOCRINOLOGY
Volume 153, Issue 5, Pages 2408-2419Publisher
ENDOCRINE SOC
DOI: 10.1210/en.2011-1822
Keywords
-
Categories
Funding
- American Diabetes Association A.D.A.
- [U54HD058155]
- [5T32DK007513-24]
- [R01DK057621]
- [P30DK02668]
- [R01HD053529]
Ask authors/readers for more resources
Leptin and melanocortin signaling control ingestive behavior, energy balance, and substrate utilization, but only leptin signaling defects cause hypothalamic hypogonadism and infertility. Although GnRH neurons do not express leptin receptors, leptin influences GnRH neuron activity via regulation of immediate downstream mediators including the neuropeptides neuropeptide Y and the melanocortin agonist and antagonist, alpha-MSH, agouti-related peptide, respectively. Here we show that modulation of melanocortin signaling in female db/db mice through ablation of agouti-related peptide, or heterozygosity of melanocortin 4 receptor, restores the timing of pubertal onset, fertility, and lactation. Additionally, melanocortin 4 receptor activation increases action potential firing and induces c-Fos expression in GnRH neurons, providing further evidence that melanocortin signaling influences GnRH neuron activity. These studies thus establish melanocortin signaling as an important component in the leptin-mediated regulation of GnRH neuron activity, initiation of puberty and fertility. (Endocrinology 153: 2408-2419, 2012)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available