Effect of metabolic fuel availability on fertility varies with reproductive state.

A 48-h fast extends the estrous cycle of virgin rats and, when instituted on days 13 and 14 postpartum (pp), prolongs lactational infertility. We investigated the ability of 2-deoxy-D-glucose (2DG) alone or combined with mercaptoacetate (MA) to mimic these effects of fasting. In Experiment 1, we monitored estrous cyclicity in virgin rats receiving 800, 1200, or 1600 mg/kg/day of 2DG during metestrus and diestrus. In Experiment 2, we assessed the effects of 2DG (1600 mg/kg/day) given on days 13 and 14 pp, on the duration of lactational infertility. In Experiment 3, the combined effects of 2DG (1600, 2000, or 2400 mg/kg/day) and MA (180 mg/kg/day) on the length of lactational diestrus were evaluated. 2DG was sufficient to extend the estrous cycle of virgin rats, but neither 2DG alone nor given with MA prolonged the length of lactational diestrus. Results suggest that lactating rats are less sensitive than virgin rats to the effects of metabolic fuel inhibition on fertility. These data are discussed in relation to the hormonal state of the dam as well as in relation to the effects of these drugs on lactational performance.

Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus, and cerebellum of normal human and alzheimer disease brains.

Assimilated evidence indicates that the neurotoxic potential of amyloid beta (Abeta) peptide and an alteration in the level of growth factor(s) may possibly be involved in the loss of neurons observed in the brain of patients suffering from Alzheimer disease (AD), the prevalent cause of dementia in the elderly. In the present study, using receptor binding assays and immunocytochemistry, we evaluated the pharmacological profile of insulin-like growth factor-I (IGF-I) receptors and the distribution of IGF-I immunoreactivity in the frontal cortex, hippocampus, and cerebellum of AD and age-matched control brains. In control brains, [(125)I]IGF-I binding was inhibited more potently by IGF-I than by Des(1-3)IGF-I, IGF-II or insulin. The IC(50) values for IGF-I in the frontal cortex, hippocampus, and cerebellum of the normal brain did not differ significantly from the corresponding regions of the AD brain. Additionally, neither K(D) nor B(max) values were found to differ in the hippocampus of AD brains from the controls. At the regional levels, [(125)I]IGF-I binding sites in the AD brain also remained unaltered compared to the controls. As for the peptide itself, IGF-I immunoreactivity, in normal control brains, was evident primarily in a subpopulation of astrocytes in the frontal cortex and hippocampus, and in certain Purkinje cells of the cerebellum. In AD brains, a subset of Abeta-containing neuritic plaques, apart from astrocytes, exhibit IGF-I immunoreactivity. These results, taken together, suggest a role for IGF-I in compensatory plasticity and/or survival of the susceptible neurons in AD brains.

Effect of acute food deprivation on lactational infertility in rats is reduced by leptin administration.

The goals of these experiments were to determine whether lactational anestrus would be prolonged by a 48-h fast at days 13 and 14 postpartum (pp) and, if so, to determine whether this effect could be reversed by treatment with the Ob protein leptin. We found that food deprivation on days 13 and 14 pp prolonged lactational infertility by 7 days and that the nutritional experience of both the dam and her litter contributed to this effect. Leptin administration (2.5 mg . kg-1 . day-1) during food deprivation was sufficient to reduce the length of lactational infertility compared with vehicle-treated food-deprived rats (P < 0.05). Similar leptin treatment in ad libitum-fed animals reduced food intake (P < 0.05) and litter growth (P < 0.05) but had no statistically significant effect on maternal weight gain or length of lactational infertility. Food-deprived lactating animals had lower circulating leptin levels than ad libitum-fed lactating animals on day 15 pp (P < 0.05), as determined by RIA. Levels in nonlactating rats were higher than in either lactating group (P < 0.05).