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SUMMARY
Some metabolic effects of cortisol were investigated in non-pregnant ewes fed either ad lib. or on a restricted ration.
Cortisol (25 mg./day) administered for a period of 21 days stimulated the voluntary food intake of fat ewes offered food ad lib. Higher levels of cortisol (50 and 75 mg./day) administered for similar periods subsequently had little additional effect on voluntary food intake, but an even greater cortisol dose (150 mg./day) resulted in a marked decline in voluntary food intake. Ewes fed a constant restricted ration did not refuse food at any time during cortisol administration.
Urinary nitrogen excretion was increased during cortisol administration but sequential increases in the cortisol dose failed to increase urinary nitrogen excretion proportionately above the level attained during administration of 25 mg. cortisol/day.
The blood glucose level was elevated progressively as the level of cortisol administered was increased. Similarly, tolerance for a glucose load was impaired progressively.
Only very small changes in blood ketones and plasma free fatty acid levels were observed during cortisol administration.
The changes in blood glucose during cortisol administration cannot be accounted for by changes in gluconeogenesis, and it is suggested that they reflect a progressive impairment of glucose utilization relative to the blood glucose level, though not a reduction in total glucose utilization.
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ABSTRACT
Insulin, glucose, lactate and alpha-amino acid nitrogen concentrations were measured in the plasma of ewes and their hypophysectomized fetal lambs during intravenous infusions of GH, prolactin or saline into the fetus in utero. Prolactin and saline had no effect on mother or fetus. Infusion of GH at 1·2 mg/kg per day for 2 days or at 0·4 mg/kg per day for 4 days caused a sustained twofold increase in the level of insulin and a smaller, but sustained, increase in the level of glucose in fetal plasma. We suggest that GH antagonizes the action of insulin in the fetus. Glucose supplies to the fetal brain and placenta may be protected by such antagonism of insulin use during glucose shortage.
J. Endocr. (1985) 105, 379–382
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Search for other papers by DENISE MADILL in
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SUMMARY
Merino ewes whose foetuses had surgically-implanted, indwelling vascular cannulae were used to determine the influence of maternal nutritional status on foetal plasma hormone levels during the last month of gestation. Observations were made during feeding of the ewes on a lucerne chaff diet ad libitum, during restricted feeding on the same diet and during fasting. Foetuses survived for an average of 31 days after the operation and seven out of the ten ewes lambed normally. In both ewes and foetuses, plasma concentrations of insulin were significantly higher 3–12 h after feeding than in prefeeding samples. Similar changes were seen with restricted and ad-libitum feeding. Fasting for 48 h caused significant decreases in insulin levels of both ewes and foetuses, but the decrease in foetal plasma insulin concentration was less than that in ewes. In agreement with earlier studies, foetal and maternal glucose concentrations were closely correlated and foetal fructose concentrations were closely related to foetal glucose concentrations. Foetal plasma insulin concentrations were closely correlated with glucose and fructose concentrations. Plasma growth hormone (GH) levels increased significantly in both ewes and foetuses during fasting. There were also significant increases during fasting in the plasma corticosteroid levels of the ewes, but not in those of their foetuses. Feeding did not cause significant changes in foetal plasma GH or corticosteroid concentrations although maternal GH concentrations were significantly increased and corticosteroid concentrations decreased 3–12 h after feeding on the restricted diet.
The results suggest that alterations in foetal plasma hormone concentrations could play an important role in foetal adaptation to fluctuations in maternal nutrient supply during the last month of gestation.
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SUMMARY
Chronically cannulated foetal lambs close to term were infused intravenously with glucose at rates of 40 or 70 mg/min for up to 5 days. Infusion at these rates increased the foetal plasma glucose concentration to values in the ranges 35–45 and 60–80 mg/100 ml respectively. There were related increases in plasma fructose and lactate concentrations.
Foetal plasma insulin concentrations increased within the first hour and remained raised throughout infusion. Plasma insulin concentrations were significantly correlated with plasma glucose concentrations. The secretory response of insulin to subsequent glucose infusions at a rate of 140 mg/min was not increased by the previous prolonged glucose infusions.
Glucose infusion resulted in decreased plasma growth hormone concentrations in three of the lambs infused, but over the total number of observations plasma glucose and growth hormone concentrations were not significantly correlated.
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Search for other papers by G. D. THORBURN in
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Prolonged pregnancy following foetal hypophysectomy or adrenalectomy (Liggins, Kennedy & Holm, 1967; Drost & Holm, 1968) and premature parturition following injection of corticotrophin or corticosteroids into the ovine foetus (Van Rensburg, 1967; Halliday & Buttle, 1968; Liggins, 1968) implicate the foetal adrenal cortex in the initiation of parturition in sheep. Consequently, foetal plasma corticosteroid concentrations and corticosteroid secretion by the foetal adrenal should be greatly increased towards term. Observations during acute studies on anaesthetized sheep suggest this (Alexander, Britton, James, Nixon, Parker, Wintour & Wright, 1968), but there is no information about blood concentrations or secretion rates of corticosteroids in normal undisturbed sheep foetuses in utero.
We cannulated the carotid artery and the facial branch of the jugular vein of four single Merino foetuses with polyvinyl chloride tubing (o.d. 1·27 mm., i.d. 0·86 mm.) with the ewes under general anaesthesia (pentobarbitone sodium (20 mg./kg., i.v.) followed by halothane and oxygen).
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SUMMARY
A sensitive method for the determination of corticosteroids in 0·1 ml. or less of ovine plasma is described. The method uses the steroid-binding properties of corticosteroid-binding globulin (CBG) and gel filtration on small columns of Sephadex G-25 (fine) at 4° for separation of CBG-bound and free steroids. Cortisol was found to be the predominant corticosteroid in ovine plasma and accounts for about 90% of the value determined by this method. The corticosteroid concentration in peripheral plasma of unstressed sheep was in the range 0·1–1·0 μg./100 ml. In untrained animals, venipuncture increased corticosteroid concentration substantially; training reduced the effect. An infusion of cortisol sodium succinate (100 μg. cortisol/min.) increased the plasma corticosteroid level to 9·5 ± 0·49 μg./100 ml. Intravenous infusion of the synthetic adrenocorticotrophic preparation Synacthen at rates of 10 and 20 μg./hr. for 2 hr. increased peripheral corticosteroid concentrations to 8 μg./100 ml. Single i.v. injections of 0·2–0·8 μg. Synacthen also significantly increased peripheral corticosteroid concentrations 7–15 min. later. The injection of 0·05 and 0·1 μg. Synacthen significantly increased the corticosteroid concentration too, but the increase was not significantly greater than that produced by the injection of acidified saline diluent alone. Injection of insulin (0·25 unit/kg. body weight, i.v.) caused a fivefold increase in the corticosteroid concentration 30–60 min. later, in both adult sheep and lambs. Glucose (0·25 g./kg. body weight, i.v.) had no effect on corticosteroid concentration.
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SUMMARY
Foetal lambs (100–150 days' gestation) with indwelling vascular catheters were used to study the regulation of the insulin concentration in the plasma of foetal lambs in utero. Immediately after the implantation of the catheters the insulin concentration in foetal plasma was significantly correlated with the foetal glucose and fructose concentrations and with the maternal glucose concentration. On the next day the foetal insulin concentration was significantly correlated only with the maternal glucose concentration.
Both glucose and fructose, when infused i.v., increased the insulin concentration in foetal plasma, but the increases were slow and far less than those observed in newborn lambs infused with glucose or fructose. Intravenous infusion of isoprenaline or glucagon did not alter the plasma insulin concentration of foetal lambs, but both caused a rapid increase in the insulin concentration of newborn lambs. Glucagon did not potentiate the insulin response to glucose. Addition of aminophylline to a glucagon infusion failed to cause insulin secretion in foetal lambs. The results suggest the cyclic-3′,5′-AMP dependent part of the insulin secretory mechanism does not develop fully before the last week of gestation.
Gel filtration of foetal plasma on Sephadex indicated that the immunoreactive material present was insulin. No significant amounts of proinsulin were found.
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SUMMARY
The effects of prolonged administration of cortisol on epithelial and dermal tissues were examined in three groups of non-pregnant ewes with different food intakes. The changes observed depended on the degree of increase in plasma cortisol and in some instances on the amount of food eaten.
Successive increases in plasma cortisol up to about 3 μg/100 ml progressively inhibited the tissues in the skin of sheep on restricted food intakes, but not those in the skin of sheep which increased their intakes. In the latter, a slight increase in plasma cortisol to about 1 μg/100 ml stimulated wool production and fibre-length growth rate. Moderate increase to about 2 μg/100 ml produced temporary enlargement of sweat glands, dilatation of capillaries and an increase in the number of dermal mast cells.
Regardless of the amount of food eaten, retrogression of all epithelial and dermal components was maximal when plasma cortisol remained above about 3 μg/100 ml. Follicle inactivation and cessation of fibre-growth occurred with the formation of brush-ends on the fibres. The retrogression of the tissues occurred in spite of increased blood glucose concentrations, indicating that cortisol depressed the utilization of glucose by the skin. Keratinization of the epidermis was altered and was possibly hastened.
The rates of recovery of the different tissues after cessation of cortisol administration were variable. Follicle regeneration and commencement of fibre regrowth were the slowest. The epidermis of the sheep on restricted food intake showed an unusual thickening.
Cortisol acetate applied topically to the skin of other sheep produced changes consistent with those induced by injected cortisol.
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Several methods are now available for the immunoassay of insulin in plasma. Of these, the double antibody technique of Hales & Randle (1963) is especially convenient. However, in studies of plasma insulin concentrations in the sheep with method C of Hales & Randle (1963), plasma samples assayed undiluted consistently yielded higher values than the same plasma samples assayed after 1:4 dilution with buffer B of Hales & Randle (1963). Addition of ovine insulin (0–200μ-u./ml.) to ovine plasma showed that the sensitivity of the assay was greater in undiluted plasma than in buffer, the decrease in antibody-bound labelled insulin for a given increment in insulin concentration being greater in the plasma system. Addition of 0·01 m-EDTA (Morgan, Sorenson & Lazarow, 1964; Sheldon & Taylor, 1965) did not eliminate this discrepancy. Insulin standards in buffer did not appear to provide a suitable baseline for assay of insulin in undiluted ovine plasma.
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SUMMARY
Plasma growth hormone (GH) concentrations in adult sheep and lambs were measured by radioimmunoassay. Mean values before feeding were 3·1 (s.e. − 0·4, + 0·5) ng./ml. in lactating ewes and 3·9 (− 0·5, + 0·7) ng./ml. in their lambs. In adult wethers the mean GH concentration before feeding was 2·3 (−0·2, + 0·3) ng./ml.
After one i.v. injection of 400 μg. ovine GH, the hormone disappeared from the plasma of adult sheep with a half-time of 7–8 min. Plasma GH concentrations decreased at a similar rate after the establishment of high concentrations of endogenously secreted GH. The results suggest a shorter half-life than has been reported for human GH in man. GH could not be recovered in an immunologically recognizable form in urine. Fasting for 4 days led to no systematic change in plasma GH concentrations. Feeding did not increase plasma GH. Intravenous injection of saline resulted in some increase in plasma GH in both ewes and lambs. In adult sheep intravenous glucose (0·25 g./kg.) did not cause any greater change than that seen after saline, but in lambs an increase occurred. Intravenous injection of insulin (0·25 unit/kg.) resulted in an increase in plasma GH at 15–30 min. and this effect was found in both lambs and ewes. Infusion of adrenaline at either 25 μg. or 50 μg./min. into adult wethers (average body wt 51 kg.) caused a decrease in plasma GH concentration. It was concluded that the changes in plasma GH concentration of sheep in a number of physiological situations differ from those reported to occur in man.
