Downregulation of LRb in VMH/DMH during the second half of gestation and upregulation of SOCS-3 in ARC in late-pregnant ewes - Implications for leptin resistance.

To investigate factors involved in pregnancy-induced regulation of tissue sensitivity to leptin, we determined leptin concentrations and expression levels of the long form of the leptin receptor (LRb) and suppressor of cytokine signalling (SOCS)-3 in the ventro- and dorsomedial nuclei (VMH/DMH), arcuate nucleus (ARC), median eminence (ME) and anterior pituitary (AP) in 15 Polish Longwool ewes euthanized at 30, 60, 90 and 120 days of pregnancy and before gestation (n = 3 per group). Leptin concentrations increased during the first half of pregnancy, peaked on day 60, and then declined. In the VMH/DMH, LRb mRNA levels decreased from day 60 of pregnancy; in the ARC, LRb mRNA levels remained stable before and throughout pregnancy. LRb expression in the ME was lower in the first two months of pregnancy than before pregnancy (P < 0.01) and peaked at day 90. In the AP, LRb mRNA levels were higher during mid-pregnancy (P < 0.05) than before pregnancy. SOCS-3 expression in the VMH/DMH was higher throughout gestation (P < 0.05) than before pregnancy but was undetectable at day 120. SOCS-3 transcript levels were higher in the ARC (P < 0.05) in late-pregnancy (at day 120) than in non-pregnant ewes. SOCS-3 mRNA levels in the ME were lower at days 30 and 60 (P < 0.05) than at day 120 or before pregnancy. In the AP, SOCS-3 transcription was stable throughout gestation except at day 120, when it increased (P < 0.05). The changes in plasma leptin concentrations during pregnancy, hypothalamic LRb downregulation in the VMH/DMH during the second half of gestation and SOCS-3 upregulation in the ARC in late-pregnant ewes identified here may be essential components of the mechanisms driving ovine leptin insensitivity.

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