The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and -MSH/cocaine and amphetamine-regulated transcript. Be- cause the central administration of leptin is capable of pre- venting the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous ad- ministration of 30 mU/d insulin or 648 g/d glucose into the cerebrospinal fluid by osmotic minipump might also have sim- ilar effects on the hypothalamic-pituitary-thyroid axis. As an- ticipated, the intracerebroventricular infusion of leptin re- duced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphet- amine-regulated transcript mRNA in the arcuate nucleus. In addition, leptin prevented fasting-induced reduction in pro- TRH mRNA levels in the paraventricular nucleus and in cir- culating thyroid hormone levels. In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, nei- ther prevented the fasting-induced suppression in hypophy- siotropic TRH mRNA or circulating thyroid hormone levels. We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential compo- nents of the hypothalamic-pituitary-thyroid regulatory sys- tem during fasting.
Differential Effects of Central Leptin, Insulin, or Glucose Administration during Fasting on the Hypothalamic- Pituitary-Thyroid Axis and Feeding-Related Neurons in the Arcuate Nucleus.
Csaba Fekete, Praful S. Singru, Edith Sanchez, Sumit Sarkar, Marcelo A. Christoffolete, Rogerio S. Riberio, William M. Rand, Charles H. Emerson, Antonio C. Bianco, and Ronald M. Lechan. Endocrinology. January 24, 2006. doi: 10.1210/en.2005-0956