Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

Leptin, a potent anorexigenic hormone secreted primarily by adipocytes, is known to be expressed in the anterior pituitary. Studies in our laboratory found leptin proteins and mRNA predominantly in somatotropes in normal male and cycling female rats. In contrast, leptin expression predominated in gonadotropes during pregnancy and lactation. Leptin expression varied with the cycle and was enhanced, in vitro by gonadotropin releasing hormone and Neuropeptide Y. In contrast, ghrelin inhibited pituitary leptin expression. Pituitary leptin in somatotropes or gonadotropes was reduced by nutritional deprivation for 24 h. However, growth hormone (GH), luteinizing hormone (LH) and pituitary leptin recovered if fasted animals were given glucose water. The glucose-mediated recovery suggests that the system is sensitive to changes in serum glucose. Somatotropes and gonadotropes also recovered if pituitary cells from fasted rats were stimulated in vitro with 1-100 pg/ml leptin. This in vitro leptin-mediated recovery suggests that leptin is important in the maintenance of somaotropes and gonadotropes. Collectively, the data suggest that pituitary leptin might serve as a “glucostat”, sensing levels of serum glucose and reporting this nutritional state to somaotropes and gonadotropes in a paracrine manner. A decrease in pituitary leptin might signal nutritional deprivation to somatotropes and gonadotropes, lowering LH and GH production and allowing for conservation of resources. Lower GH would help conserve fat stores and lower LH would promote survival over reproduction.