Progesterone displays a strong potential for the treatment of neonatal hypoxic-ischemic encephalopathy since it has been shown to be beneficial in the treatment of the central nervous system injuries in adult animals. Here, we evaluated the effects of the administration of progesterone (10 mg/kg) in seven-days-old male Wistar rats submitted to neonatal hypoxia-ischemia (HI). Progesterone was administered immediately before ischemia and/or 6 and 24 h after the onset of hypoxia. The body weight of the animals, the volume of brain lesion and the expression of p-Akt and procaspase-3 in the hippocampus were evaluated. All animals submitted to HI showed a reduction in the body weight. However, this reduction was more remarkable in those animals which received progesterone before surgery. Administration of progesterone was unable to reduce the volume of brain damage caused by HI. Moreover, no significant differences were observed in the expression of p-Akt and procaspase-3 in animals submitted to HI and treated with either progesterone or vehicle. In summary, progesterone did not show a neuroprotective effect on the volume of brain lesion in neonatal rats submitted to hypoxia-ischemia. Furthermore, progesterone was unable to modulate p-Akt and procaspase-3 signaling pathways, which may explain the absence of neuroprotection. On the other hand, it seems that administration of progesterone before ischemia exerts some systemic effect, leading to a remarkable reduction in the body weight.
Stanniocalcin-1 and -2 belong to a family of molecules that exhibit both paracrine and autocrine effects in mammalian cells. Human stanniocalcin-1 (hSTC-1) is expressed in a wide range of tissues, including white adipose tissue. In fed rats, hSTC-1 increases carbon flux from glucose to lipids in retroperitoneal white adipose tissue. Human stanniocalcin-2 (hSTC-2) is expressed in almost all tissues and regulates various biological processes. The aim of this work was to study the action of hSTC-1 and hSTC-2 in the lipid and glucose metabolism of epididymal white adipose tissue (eWAT) in rats in different nutritional states. This study shows for the first time an opposite effect of hSTC-1 and hSTC-2 on glyceride-glycerol generation from glucose in eWAT of fed rats. hSTC-1 stimulated the storage of triacylglycerol in eWAT in the postprandial period, increasing glucose uptake and glyceride-glycerol generation from 14C-glucose. hSTC-2 decreased triacylglycerol synthesis, reducing glyceride-glycerol generation from 14C-glucose, direct phosphorylation of glycerol, and fatty acid synthesis from 14C-glucose in eWAT of fed rats. However, both hormones increased glucose uptake in fed and fasting states. These findings provide evidence for a direct role of hSTC-1 and hSTC-2 in the regulation of lipid and glucose metabolism in eWAT of rats.
Neonatal hypoxia-ischemia (HI) is the leading cause of mortality and morbidity in newborns, occurring in approximately 2% of live births. Neuroprotective actions of progesterone (PROG) have already been described in animal models of brain lesions. However, PROG actions on neonates are still controversial. Here, we treated male Wistar rats exposed to HI with PROG. Five experimental groups were defined (n = 6/group) according to the scheme of PROG administration (10 mg/kg): SHAM (animals submitted to a fictitious surgery, without ischemia induction, and maintained under normoxia), HI (animals undergoing HI), BEFORE (animals undergoing HI and receiving PROG immediately before HI), AFTER (animals undergoing HI and receiving PROG at 6 and 24 h after HI) and BEFORE/AFTER (animals undergoing HI and receiving PROG immediately before and 6 and 24 h after HI). At P14 (7 days following HI), the volumes of lesion of the cerebral hemisphere and the hippocampus ipsilateral to the cerebral ischemia were evaluated, along with p-Akt, cleaved caspase-3 and GFAP expression in the hippocampus. PROG reduces the loss of brain tissue caused by HI. Moreover, when administered after HI, PROG was able to increase p-Akt expression and reduce both cleaved caspase-3 and GFAP expression in the hippocampus. In summary, it was possible to observe a neuroprotective action of PROG on the brain of neonatal animals exposed to experimental HI. This is the first study suggesting PROG-dependent Akt activation is able to regulate negatively cleaved caspase-3 and GFAP expression protecting neonatal hypoxic-ischemic brain tissue from apoptosis and reactive gliosis.
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