Jean-Pierre Barlet

Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were investigated in adult (7-month-old) Wistar rats. Forty animals were ovariectomised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) microg/g body weight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD) excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were similar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was similar to that in SH rats, its value was lower in IF20 rats than in controls. The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-induced bone loss, both by depressing bone resorption and stimulating osteoblast activity. Moreover, as only the highest IF level induced a weak uterotrophic activity, the optimal IF dose which preserves both cancellous and cortical bone, but exhibits no oestrogen-like effects on the uterus, was 40 microg/g body weight per d.

Nutrient effects on the hepatic production of somatomedin C (IGF,) in the milk-fed calf

The present study was aimed at determining the influence of nutrients supplied by a milk diet (glucose, amino acids, triglycerides) on hepatic somatomedin C (IGFi) production in vivo in four 30-d-old milk-fed calves fitted with chronically indwelling catheters in hepatic (HV), portal (PV) and mesenteric veins and in the hepatic artery (HA), and with electromagnetic flow-meters on HA and PV. Fasting for 16 h induced a decrease (P less than 0.01) in hepatic IGF1 production (nmol/kg body-weight (BW) for 6 h) (1.1 (SE 0.2) v. 6.6 (SE 0.7) in control animals). Infusion of glucose (1.8 g/kg BW for 4 h) or a mixture of amino acids (Azonutril; R. Bellon, Neuilly sur Seine; 62.5 mg nitrogen/kg BW for 3 h) in a mesenteric vein led to no significant effect on hepatic IGF1 production for 6 h (1.2 (SE 0.3) and 0.7 (SE 0.3) nmol/kg BW respectively) compared with fasted calves. Infusion of chylomicrons purified from milk-fed calves (10.5 mg/h per kg BW, i.e. 0.16 mg triglycerides/kg BW per min) enhanced significantly (P less than 0.01) the hepatic production of IGF1 (mean value for 6 h: 5.3 (SE 0.8) nmol/kg BW). Infusion of Intralipid (7 mg triglycerides/kg BW per min) induced a slight but significant hepatic IGF1 production which amounted to 3.5 (SE 0.4) nmol/kg BW (P less than 0.1 compared with chylomicron treatment) and it began only 5 h after starting the infusion. Neither triglyceride nor chylomicron infusion significantly modified hepatic blood flow. Thus, these results demonstrate for the first time the role of lipids in the regulation of hepatic IGF1 production in vivo.

Steroid Hormone May Modulate Hepatic Somatomedin C Production in Newborn Calves

We have studied the possible influence of steroid hormones and a beta-agonist (clembuterol) on hepatic insulin-like growth factor 1 (IGF1) production in young calves. For this purpose nine 20- to 40-day-old Holstein X Friesian male calves were fitted with chronically indwelling catheters in hepatic and portal veins and hepatic artery. Estradiol induced a simultaneous increase in plasma growth hormone (GH nmol/l) and IGF1 (nmol/l) levels (0.35 +/- 0.05 vs. 0.10 +/- 0.01 in control calves; 9.5 +/- 1.0 vs. 5.9 +/- 0.5 in controls, respectively). In the same way, 90 min after starting testosterone treatment, plasma GH levels increased from 0.21 +/- 0.08 to 1.30 +/- 0.40 while plasma IGF1 concentrations began to rise only 240 min after starting infusion (8.4 +/- 1.0) to reach maximal values at 300 min (10.7 +/- 1.1). Cortisol and clembuterol did not significantly modify either plasma GH levels or plasma IGF1 concentrations. Our results indicate that in young calves gonadal steroids exert their anabolic action through GH and IGF1.

Regulation of Growth Hormone Release in Fetal Calves

Plasma GH and IGF1 concentrations were measured during the last 2 months of gestation in 9 chronically catheterized fetal calves under basal conditions or following growth-hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) or SRIF intravenous cotyledonnary injections. Plasma GH concentrations were higher in fetuses (1.40 +/- 0.10 nmol/l) than in dams (0.14 +/- 0.01 nmol/l). Plasma GH secretory profile was pulsatile. The number of secretory pulses, as well as their magnitude and mean baseline values decreased from 220 to 270 days of gestation. Synthetic 1-29 GRF or TRH increased fetal plasma GH concentration at 250 and 270 days of gestation but was devoid of any significant effect at 220 days. SRIF injection decreased plasma GH concentration in 270-day-old fetuses. Plasma IGF1 concentrations were lower in fetuses than in dams. No treatment had a significant effect on fetal and maternal IGF1 levels.

Plasma Calcium Homeostasis in the Guinea Pig during the Perinatal Period

In pregnant guinea pigs on day 60 of gestation, maternal hypercalcemia induced by calcium infusion (10 mg Ca/kg body weight/h, during 2 h) had no significant effect on the fetal plasma calcium level. By contrast, on day 66 of gestation the same infusion of calcium into the pregnant female induced a significant rise both in maternal and fetal plasma calcium levels. This difference might be related to the variations in the efficiency of placental calcium transfer occurring during the last days of gestation in the guinea pig. Plasma calcium, phosphate and magnesium levels decrease during the 12 h following birth in suckling guinea pigs. Plasma calcium and magnesium concentrations returned to normal values at 24 h while plasma phosphate levels increased during the first week of postnatal life.

Influence of Kinetics of Gastric Emptying on Hepatic IGF1 Production in Young Calves

Five preruminant calves, fitted with chronically indwelling catheters in the hepatic and portal veins and hepatic artery, were fed two kinds of diet (a conventional clotting milk diet and an incurdled milk diet) or fasted for 24 h. The statistical analysis of the plasma growth hormone (GH; nmol/l) or IGF1 (nmol/l) daily secretory profiles indicated that hormonal levels were very high in fed calves (GH mean values: 0.40 +/- 0.11 and 0.36 +/- 0.10, respectively; IGF1 mean values: 6.65 +/- 0.57 and 7.54 +/- 0.33, respectively). The GH secretory profile observed over a 24-hour period showed 7 secretory spikes without periodicity in both diets. In fasting animals, plasma GH and IGF1 concentrations were very low (0.17 +/- 0.08 and 3.08 +/- 0.36, respectively) and stable, they increased with refeeding (1.51 +/- 0.05 and 7.36 +/- 0.55, respectively). Hepatic IGF1 production (micrograms/kg body weight/day) was 195 +/- 7 in standard milk fed calves and -255 +/- 30 in others. Our results demonstrated that nutritional factors, such as different kinetics of gastric emptying or fasting, may influence hepatic IGF1 production in the conscious newborn calf.