In vitro and in vivo regulation of hepatic erythropoiesis by erythropoietin and glucocorticoids in the rat fetus.

Glucocorticoids affect evolution of rat fetal liver erythropoietic tissue, where their receptors have been characterized. This paper describes erythropoietin (Ep) and dexamethasone (Dex) effects on the number of CFUE and BFUE grown from erythroid cells isolated from 14 day fetal livers. CFUE number showed a linear log dose-response towards Ep. In absence of exogenous Ep, it was increased by 10(-10) - 10(-9) mol/L Dex. At Ep concentrations less than or equal to 0.025 U/ml, it was increased by Dex concentrations less than or equal to 10(-9) mol/L, higher Dex concentrations being inhibitory. At Ep concentrations greater than 0.025 U/ml, only a linear log dose inhibitory effect of Dex was observed, related to receptor occupancy. BFUE number was not affected by Dex. Ep activity of fetal serum, measured by CFUE induction, was high at 15-16 days of gestation and much lower thereafter. Proliferation of erythropoietic tissue in rat fetal liver before 16 days probably results from high Ep and low corticosterone levels; the regression of proliferation after 16 days probably results from the reverse hormonal status.

Evidence for fibrinogen synthesis and secretion by rat foetal hepatocytes.

Fibrinogen concentration in rat foetal plasma is very low at 18 days of gestation but increases rapidly thereafter. The present study provides evidence that this increase is due to synthesis by the foetus itself. (1) 125I-labelled human fibrinogen, injected intravenously into the pregnant adult, did not reach the foetal circulation; (2) turpentine administration to the adult induced an increased maternal plasma fibrinogen concentration without affecting the foetal one; (3) conversely, in utero administration of turpentine to foetuses increased their plasmas fibrinogen concentration without affecting the maternal one; (4) using sheep anti-rat fibrinogen antibodies labelled with peroxidase, in electron microscopy, fibrinogen was located in foetal hepatocytes within the organelles known to be responsible for the synthesis and the ultimate secretion of the protein.

Effects of sub-total gastro-intestinal pancreatectomy of the rat foetus.

Sub-total pancreatectomy in utero was performed in 18-day-old rat foetuses. Pancreatectomized, sham-operated and control foetuses were collected 3 days later and body weight, glucose and insulin levels in blood, and glycogen content and glucose-6-phosphatase (G-6-Pase) activity of the liver were determined. Pancreatectomized foetuses showed only very small pancreatic remnants (less than or equal to 1 mg) and accordingly their insulin levels were much lower (four to five times) than those of sham-operated or control foetuses; their blood glucose levels were slightly increased and liver glycogen content and G-6-Pase activity were slightly reduced; their body weights were also reduced. These results are discussed in relation to other relevant data in the literature. They afford direct experimental evidence of the endogenous origin of insulin in the foetal blood. It is suggested that during the last days of intra-uterine life insulin merely completes the action of the glucocorticoids on glycogen storage in rat foetal liver and probably contributes to foetal body growth. Its relative ineffectiveness on the foetal blood glucose level is not explained. As pancreatectomized foetuses develop sub-normal liver G-6-Pase activity, glucagon is probably not responsible for the increase in this activity occurring during normal development before birth.