Evidence for hypothalamic control of fetal leptin secretion during late gestation

Abstract

Objective: In the adult sheep, leptin synthesis and secretion in adipose tissue is regulated by a range of factors including the external photoperiod, hypothalamic neuropeptides and peripheral nutrient and hormonal signals. While it has been established that leptin is synthesised in adipose tissue and is present in the circulation before birth, it is not known whether the external photoperiod or fetal hypothalamus plays a role in the regulation of leptin synthesis or secretion in late gestation. We have utilised a model of hypothalamo-pituitary disconnection (HPD) in which the neural tissues of the median eminence and surrounding arcuate nucleus are removed, and a physical barrier is inserted above the pars tuberalis to separate the hypothalamus and pituitary to investigate the role of the hypothalamus in the tonic regulation of fetal leptin in ewes held under long light (LL:1 6h L:8h D) or short light (8hL:l6hD) conditions. Methods: Twenty three ewes were housed in a I2hL:12D regime until surgery between 106 and 120d gestation.HPD was performed in the fetuses of 10 ewes and a sham procedure carried out in 13 fetuses. Six ewes (HPD group) and 6 ewes (intact group) were moved into a LL regime, whereas 4 ewes (HPD group) and 7 ewes (intact group) were moved into a SL regime. Maternal and fetal blood samples were collected throughout late gestation until 142d gestation. The completeness of the HPD procedure was confirmed using the lack of a proalctin response to a chlorpromazine challenge as previously described. Plasma leptin concentrations were measured using an ELISA and the effects of photoperiod and HPD on leptin concentrations were determined using a multifactorial Analysis of Variance and repeated measures. Results: In the ewes, there was no effect of varying the length of the photoperiod or of carrying an HPD fetus on maternal plasma concentrations of leptin. There was also no effect of external photoperiod on fetal plasma leptin concentrations. Fetal plasma leptin concentrations were significantly higher, however, in the HPD fetal sheep (LL, 5.9 ± 1.3 ng/ml: SL, 7.9 ± 2.6 ng/ml) than in the intact group (LL, 4.7 ± 0.8 ng/ml: SL, 4.0 ± 1.4 ng/ml) throughout late gestation Conclusion: We have demonstrated that surgical disconnection of the fetal hypothalamus and the pituitary results in an increase in circulating leptin throughout late gestation. This suggests that either the mediobasal region of the fetal hypothalamus or the fetal pituitary act to inhibit leptin synthesis or secretion throughout late gestation.