High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.

In the adult mammal the circadian system, which allows predictive adaptation to daily environmental changes, comprises peripheral oscillators in most tissues, commanded by the suprachiasmatic nucleus (SCN) of the hypothalamus. The external environment of the fetus is provided by its mother. In primates, maternal melatonin is a candidate to entrain fetal circadian rhythms, including the SCN rhythms of metabolic activity. We found in the 90% of gestation capuchin monkey fetus expression of the clock genes Bmal-1, Per-2, Cry-2, and Clock in the SCN, adrenal, pituitary, brown fat, and pineal. Bmal-1, Per-2, and the melatonin 1 receptor (MT1) showed a robust oscillatory expression in SCN and adrenal gland, whereas a circadian rhythm of dehydroepiandrosterone sulphate was found in plasma. Maternal melatonin suppression changed the expression of Bmal-1, Per-2, and MT1 in the fetal SCN. These effects were reversed by maternal melatonin replacement. In contrast, neither maternal melatonin suppression nor its replacement had effects on the expression of Per-2 and Bmal-1 or MT1 in the fetal adrenal gland or the circadian rhythm of fetal plasma dehydroepiandrosterone sulphate. Our data suggest that maternal melatonin is a Zeitgeber for the fetal SCN but probably not for the adrenal gland.

We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[125 I] iodomelatonin binding (K d , 75.7 ± 6.9 pM; B max , 2.6 ± 0.4 fmol (mg protein) −1 ), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)-and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTHinduced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4-to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light-dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.

To investigate the changes in maternal bone density and turnover associated with lactation we ran a longitudinal study in fully breastfeeding women (age 26.3 +/- 4.1 years, mean +/- SD) at the first (stage I, n = 30) and sixth (stage II, n = 25) months postpartum and 6 months after weaning (stage III, n = 20), and in a contemporary control group of non-nursing women. At each time point bone density, serum calcium, phosphorus, alkaline phosphatases, parathyroid hormone (PTH), osteocalcin, follicle stimulating hormone (FSH), estradiol (E2), prolactin (PRL) urinary hydroxyproline and creatinine (OH-P/Cr) were measured in both groups. The daily calcium intake of nursing women (1479 +/- 590 mg/day at stage I) was higher than in non-nursing women (536 +/- 231 mg/day at stage I). Biochemical markers of bone turnover were higher (p < 0.05) in nursing than in non-nursing women at stages I and II, while in stage III only OH-P/Cr was elevated. The lumbar spine (L2-4) bone mineral density was similar in the two groups at the beginning of the study (1.148 +/- 0.111 g/cm2 in nursing women vs 1.211 +/- 0.102 g/cm2 in non-nursing women; p = 0.06), but it was lower in nursing women at stage II (1.144 +/- 0.110 g/cm2 vs 1.216 +/- 0.095 g/cm2 respectively; p < 0.05). Right femoral neck bone density decreased by 3% between stages I and II in nursing women but did not differ from values in non-nursing women (0.947 +/- 0.110 vs 0.973 +/- 0.108 in stage I and 0.918 +/- 0.114 vs 0.975 +/- 0.098 in stage II respectively; p < 0.05, ANOVA). After weaning, lumbar spine and femoral neck bone density increased by 6% and 8% respectively (p < 0.05, ANOVA). No correlation was found between changes in bone turnover markers or bone density and parity, frequency and duration of nursing episodes, body weight, body mass index, and plasma PRL, E2 and PTH levels. We conclude that in nursing women with a daily calcium intake at the recommended dietary allowance ( > 1200 mg/day), full breastfeeding extending over 6 months is characterized by increased maternal bone turnover and a transient bone loss which normalizes after weaning.