Parturition in sheep is initiated by a rapid rise in fetal plasma cortisol. There is some controversy as to the exact nature of the drive for this pre-partum cortisol surge and it is thought that factors other than ACTH may act in concert to stimulate the development of the fetal adrenal gland. We have investigated the concentrations of ACTH and other peptides derived from pro-opiomelanocortin (POMC) in the circulation of fetal sheep during the final part of gestation, using specific 2-site immunoradiometric assays. The expected rise in fetal cortisol was seen with an 880% (p < 0.01) increase in concentration of this hormone between the initial measurement period (110-119 days gestation) and the final period (139-147 days). Fetal plasma ACTH increased less dramatically (137%; p < 0.03) during this time. The most surprising finding was the presence of very high relative concentrations of the N-terminal POMC peptide N-POMC(1-77) in the fetal circulation. Initially the concentration was 289 +/- 66 pmol/l compared to ACTH concentrations of 6.4 +/- 0.8 pmol/l. In the final week of gestation N-POMC(1-77) levels, although still high, had declined to 188 +/- 35 pmol/l (ACTH having increased to 13.7 +/- 2.2 pmol/l). Fetal plasma 3 yen-MSH was found to increase towards the end of gestation when the concentration of N-POMC(1-77) was declining, suggesting some cleavage of the latter. We postulate that the N-POMC(1-77) and its fragments, acting in concert with ACTH, play a vital role in stimulating the development of the fetal adrenal cortex and provide the additional drive to the adrenal gland required to stimulate parturition.

I. In order to establish whether or not there is a relationship between the blood ketone-body concentrations and the potential ability of the liver to synthesize ketone bodies in sheep on varying nutritional regimens, a study has been made of the concentrations of acetoacetate and 3-hydroxybutyrate in blood and the activities of enzymes concerned with ketogenesis in liver of developing sheep from mid-way through gestation to maturity, in pregnant ewes from mid-way through pregnancy and in starved pregnant and non-pregnant ewes.2. During development the most marked change in blood 3-hydroxybutyrate concentration occuried when the lambs were weaned. Blood acetoacetate concentrations did not change during development. When mature ewes were starved both 3-hydroxybutyrate and acetoacetate concentrations in blood were increased.3. Changes found in the activity of 3-hydroxybutyrate dehydrogenase (EC I . I . I .30) in the liver were correlated with the changes in blood 3-hydroxybutyrate concentrations during development but no such relationship existed in pregnant or fasted ewes. No correlation was found between the ability of the liver to synthesize acetoacetate and blood ketone body concentrations in either developing or pregnant adult sheep. The rate of acetoacetate production expressed per g liver increased during foetal life but values observed in lambs I d after birth were similar to those found in suckling and mature sheep. During the last month of pregnancy and when non-pregnant sheep were starved the hepatic potential for ketogenesis was increased. During development the activity of acetyl-CoA acetyltransferase (EC 2.3. I .g) was correlated with the rate of hepatic acetoacetate production.4. These changes have been contrasted with those that occur in developing and starved adult rats. 5. It is concluded that hepatic production of ketone bodies cannot be the only factor in the regulation of blood ketone body concentrations in developing and pregnant sheep. , 1969) indicates that changes must occur in blood ketone-body concentrations during development in this species. These changes may result from changes in either the rate of production of ketone bodies or the rate of their irreversible loss. During the development of the rat Bailey & Lockwood (1973) have found that there are marked changes in the ability of the liver to synthesize ketone bodies and this enhanced potential for ketogenesis appears to be closely related to blood ketone-body concentrations. These changes have been attributed to the varying dietary regimens of the rat at birth, during suckling and when weaned onto a high-carbohydrate diet. In the adult rat, in contrast to the newborn rat, the ketosis of starvation is not accompanied by any marked increase in the activity of the enzymes of hepatic ketogenesis (Williamson, Bates & Krebs, 1968).In ruminants there are two major sites of ketogenesis, namely the wall of the reticulorumen and the liver. The relative amounts of ketone bodies originating from these two organs will vary with the stage of de...

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