DISTURBANCE OF THE REPRODUCTIVE AXIS INDUCED BY NEGATIVE-ENERGY BALANCE

Animal reproduction is impaired when intake of energy is so restricted that activities essential to life are threatened; this is seen as a h omeostatic adjustment that restricts wasteful energy expenditure. Fast ing or exercising to a degree requiring considerable energy expenditur e has major effects on the hypothalamus, including activation of corti cotrophin-releasing factor (CRF) neurons, suppression of thyrotrophin- releasing hormone synthesis, and increased growth hormone secretion; t hese are associated with increased concentrations of hypothalamic neur opeptide Y mRNA and are corrected by administration of leptin, an adip ose-tissue protein with a tertiary structure similar to the cytokine i nterleukin-2. This response to fasting results from a disordered patte rn of activity in the gonadotrophin-releasing hormone (GnRH) pacemaker , characterized by reduced luteinizing hormone pulsatility, particular ly during daytime. Animal studies have suggested that the response dep ends on an intact afferent vagal system from the stomach and the prese nce of oestrogen. Noradrenergic neurons forming the A(2) group increas e the activity of CRF neurons that, in turn, inhibit GnRH pulsatility. Reproductive impairment due to fasting is reversed by leptin, and abn ormalities of leptin are described in individuals who fast or who deve lop exercise-induced amenorrhoea. This paper discusses these changes i nduced by negative energy balance and speculates on the involvement of leptin as a contributor to these abnormalities.