Nutrition and ovarian physiology

Puberty, ovulatory process and reproductive functions are dependent of energy 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 maturation, menstrual cycle and fertility. In comparison with the extreme forms of nutritional disorders - ie anorexia or bulimia nervosa and obesity - more frequent and subtle pathologic eating behavior associated or not with weight changes have been recognized as associated factors possibly involved in numerous ovulatory disorders. Independently of the weight, the abdominal distribution of Fat seems to have a deleterious effect on female fecondity. The waist-to-hip ratio is positively correlated to the prevalence of oligomenorrhea. WHR is negatively correlated to the conception rate of women. There is evidence that weight, body composition, fat distribution and eating habits may modulate the clinical expression as well the biological intensity of androgen excess. While it is acknowledged that the appearance and the maintainance of reproductive function is highly dependent on nutrition and energetic balance, we don't know how the communication occurs at the cellular and molecular level. It is clear that the brain and hypothalamic structures receive an endocrine and/or metabolic signal providing information on the nutritional status and the degree of fat stores. Several candidates have been implicated as possible link between nutritional state and the function of the hypothalamic-pituitary-ovarian axis: (1) alterations in general energy availability testified by low T3 and changes in basal energy expenditure, (2) variations in more specific metabolic fuels as free fatty acids or glucose, (3) changes in peripheral hormonal signals as insuline, growth factors (IGFI, IGFII) and related binding proteins and, interestingly, in leptin. Among the humoral signals informing the reproductive axis about nutritional status, leptin is growingly emerging as a convincing hypothesis. Plasma levels of leptin are correlated with the degree of obesity and are regulated by feeding and fasting. In the leptin-deficient female ob/ob mice, treatment with leptin, increases serum levels of LH and ovarian and uterine weight compared to pair-fed controls, and restores fertility. Since rodents hypothalamus express the leptin receptor gene, the leptin-induced rise in gonadotropins probably proceeds from an effect on the reproductive neuroendocrine system. A direct ovarian action of leptin has also been demonstrated in rat ovarian granulosa cells, where leptin counteracts the synergistic effect of IGF-I on FSH-stimulated estradiol production. In human, the leptin receptor gene is expressed in hypothalamus and, ovary, and leptin reduce the production of estradiol by granulosa cultured cells. Finally, the recent development concerning the effect of leptin on reproductive function offers a new lighting on tigh interrelationships between nutrition and reproductive function and reinforces the importance to consider the nutritional mechanisms in numerous ovulatory disorders.