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SUMMARY1. Plasma concentrations of cortisol and corticosterone measured by competitive protein binding in rats between 5 and 28 days after birth have been related to the intestinal uptake of [1251]polyvinyl pyrrolidone (PVP).2. Plasma cortisol concentration was consistently low throughout the period studied, but there was an increase in plasma corticosterone concentration at the time (18-21 days) when PVP uptake declined to zero (closure).3. Injection of a large dose of cortisone acetate 5 days after birth resulted in precocious closure; PVP uptake declined progressively to zero during the 6 days following the injection. Injection of this steroid at 12 days of age caused closure within 4 days.4. Precocious closure induced by cortisone acetate was closely comparable histologically with natural closure; the decline in PVP uptake was associated with the progressive displacement of vacuolated cells from the villi of the terminal intestine.5. Injection of corticosterone at either 5 or 12 days after birth also reduced PVP uptake. However, the reduction was transient and uptake returned to control levels some days after the injection.6. The temporary reduction in PVP uptake following corticosterone injection was not associated with any change in the histological appearance of the small intestine at the light microscope level.7. The injection of either cortisone acetate or corticosterone was followed by a period of impaired body growth and also a reduction of adrenal weight in animals injected at 12 days but not in animals injected at 5 days.

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Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uninucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be suppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.Fetal pituitary stalk section [Liggins, Fairclough, Grieves, Kendall and Knox, 1973], fetal hypophysectomy [Liggins, Kennedy and Holm, 1967] or bilateral fetal adrenalectomy [Drost and Holm, 1968] all prolong the period of gestation in the ewe beyond the normal limit of 145-150 days. Although the fetal endocrine status differs with each type of experimental preparation [Liggins et al., 1973; Nathanielsz, Jack, Krane, Thomas, Ratter and Rees, 1977], parturition can still be induced after the 100th day of gestation by fetal infusion of cortisol, or, in the presence of intact adrenals, of ACTH. This finding may have deflected attention from the effects of interruption of the hypothalamo-pituitary-adrenalplacental pathway on the target organ, the placenta.Barnes, Comline, Silver and Steven [1976] have recently shown that changes in the ultrastructural arrangements of the placenta follow fetal hypophysectomy or fetal adrenalectomy. In this investigation we have widened the field of enquiry by ultrastructural examination of the placentae of fetal lambs after section of the pituitary stalk at 108-109 days gestation. Preliminary reports of some of this work have been presented elsewhere [Steven, 1977;Bass, Krane, Mallon, Nathanielsz, Steven and Thomas, 1977]. METHODS Eleven Welsh Mountain ewes were used in this study. Six were unoperated uninfused control animals at 120, 121, 128, 130, 132 and 139 days of gestation. 4 fetuses of 3 ewes were stalk sectioned and catheterized at 108-109 days of gestation and subsequently infused with saline, cortisol or ACTH (Table I; SN 548, 572,. The fetuses of the two further ewes 221

4. There was no constant relation between aldosterone and glucocorticoid concentrations in the animals studied, either new-born or adult.5. Plasma cortisol: corticosterone ratios were not constant but varied considerably. In the adult a sevenfold rise in plasma cortisol concentration occurred under certain conditions without any change in plasma corticosterone concentrations.