Effect of food restriction on reproductive-related genes and reproductive hormones in adult female rats.

OBJECTIVES: A number of factors involved in the control of energy balance and metabolism act as modulators of gonadal axis. Ghrelin, a peptide secreted from the stomach and hypothalamus, has emerged as an orexigenic food intake controlling signal acting upon hypothalamus. Recently, the potential reproductive role of ghrelin has received great attention. This study was designed to investigate the influence of food restriction and consequent metabolic hormone (ghrelin) on the level and gene expression of female reproductive hormones in adult rats. MATERIALS AND METHODS: To study the effect of chronic food restriction on ghrelin level in adult female rats and its relation to female reproductive hormones, 32 adult female Sprague Dawley rats divided into 4 groups: Group I (control group) comprised 8 rats fed ad libitum for 30 days, Group II, III and IV (food-restricted groups for 10, 20 and 30 days respectively) each consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food consumed by the control group. RESULTS: Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced significant increase of serum ghrelin with significant decrease of both gastric and hypothalamic ghrelin accompanied with significant increase in its gene expression in stomach and hypothalamus. Estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed significant decrease correlated with down-regulation of gonadotropins, cyclin-dependent kinase (cdc2), cyclin B and kisspeptin (Kiss1) genes in food restricted rats compared with control group. CONCLUSIONS: Ghrelin could be one of the hormones responsible for the suppression of female reproductive axis in case of negative energy balance. Thus, ghrelin may operate as an autocrine/paracrine regulator of ovarian function. Overall, ghrelin may represent an additional link between body weight homeostasis and reproductive function.