Nutrition and ovarian physiology

Puberty, ovulatory process and reproductive functions are dependent of ener gy resources. The role of weight body composition, fat distribution and the effect of diet and exercice have largely been investigated in women where their alterations may induce overt abnormalities in timing of sexual matura tion, menstrual cycle and fertility. In comparison with the extreme forms o f nutritional disorders - ie anorexia or bulimia nervosa and obesity - more frequent and subtle pathologic eating behavior associated or not with weig ht changes have been recognized as associated factors possibly involved in numerous ovulatory disorders. Independently of the weight, the abdominal di stribution of Fat seems to have a deleterious effect on female fecondity. T he waist-to-hip ratio is positively correlated to the prevalence of oligome norrhea. WHR is negatively correlated to the conception rate of women. Ther e is evidence that weight, body composition, fat distribution and eating ha bits may modulate the clinical expression as well the biological intensity of androgen excess. While it is acknowledged that the appearance and the ma intainance of reproductive function is highly dependent on nutrition and en ergetic balance, we don't know how the communication occurs at the cellular and molecular level. It is clear that the brain and hypothalamic structure s receive an endocrine and/or metabolic signal providing information on the nutritional status and the degree of fat stores. Several candidates have b een implicated as possible link between nutritional state and the function of the hypothalamic-pituitary-ovarian axis: (1) alterations in general ener gy availability testified by low T3 and changes in basal energy expenditure , (2) variations in more specific metabolic fuels as free fatty acids or gl ucose, (3) changes in peripheral hormonal signals as insuline, growth facto rs (IGFI, IGFII) and related binding proteins and, interestingly, in leptin . Among the humoral signals informing the reproductive axis about nutrition al status, leptin is growingly emerging as a convincing hypothesis. Plasma levels of leptin are correlated with the degree of obesity and are regulate d by feeding and fasting. In the leptin-deficient female ob/ob mice, treatm ent with leptin, increases serum levels of LH and ovarian and uterine weigh t compared to pair-fed controls, and restores fertility. Since rodents hypo thalamus express the leptin receptor gene, the leptin-induced rise in gonad otropins probably proceeds from an effect on the reproductive neuroendocrin e system. A direct ovarian action of leptin has also been demonstrated in r at ovarian granulosa cells, where leptin counteracts the synergistic effect of IGF-I on FSH-stimulated estradiol production. In human, the leptin rece ptor gene is expressed in hypothalamus and, ovary, and leptin reduce the pr oduction of estradiol by granulosa cultured cells. Finally, the recent deve lopment concerning the effect of leptin on reproductive function offers a n ew lighting on tigh interrelationships between nutrition and reproductive f unction and reinforces the importance to consider the nutritional mechanism s in numerous ovulatory disorders.