Disturbance of the reproductive axis induced by negative energy balance

Abstract

Animal reproduction is impaired when intake of energy is so restricted thatactivities essential to life are threatened; this is seen as a homeostaticadjustment that restricts wasteful energy expenditure. Fasting or exercisingto a degree requiring considerable energy expenditure has major effects on thehypothalamus, including activation of corticotrophin-releasing factor (CRF)neurons, suppression of thyrotrophin-releasing hormone synthesis, andincreased growth hormone secretion; these are associated with increasedconcentrations of hypothalamic neuropeptide Y mRNA and are corrected byadministration of leptin, an adipose-tissue protein with a tertiary structuresimilar to the cytokine interleukin-2.This response to fasting results from a disordered pattern of activity in thegonadotrophin-releasing hormone (GnRH) pacemaker, characterized by reducedluteinizing hormone pulsatility, particularly during daytime. Animal studieshave suggested that the response depends on an intact afferent vagal systemfrom the stomach and the presence of oestrogen. Noradrenergic neurons formingthe A2 group increase the activity of CRF neurons that, in turn, inhibit GnRHpulsatility. Reproductive impairment due to fasting is reversed by leptin, andabnormalities of leptin are described in individuals who fast or who developexercise-induced amenorrhoea. This paper discusses these changes induced bynegative energy balance and speculates on the involvement of leptin as acontributor to these abnormalities.