Physiological perspectives on leptin as a regulator of reproduction: role in timing puberty.

How nutrition regulates reproductive activity remains a major unsolved question of reproductive biology. Reducing the level of nutrition during adulthood can lead to infertility, primarily through reduction of GnRH secretion. Inquiry about such a mechanism has its roots in the search for cues timing the onset of fertility, because the tempo of sexual maturation is much more closely associated with body growth than with chronological age. Growth depends on the quantity and quality of food intake. When food availability is low, small, short-lived species with high metabolism and reduced growth may not even attain puberty before they die. In longer-lived species, puberty is delayed for months or even years until more food becomes available. To appreciate fully how the pubertal progression is timed will require understanding how peripheral signals relating information about energy metabolism are sensed by the brain and how such information is routed through pathways controlling GnRH secretion. Here, we provide some background and physiologic perspective on the question of whether the fat-derived hormone leptin is the unique peripheral signal, is an important signal, is but one of a constellation of signals, or is not a signal timing puberty.