A marked increase in sympathoadrenal activity at birth has been described in animals and humans. Studies to determine whether the magnitude and duration of the catecholamine surge at birth in preterm lambs is similar to full-term lambs were undertaken using an acutely exteriorized fetal lamb. To maintain a physiologically stable preparation, all preterm lambs were given natural sheep surfactant intratracheally before the first breath. Base-line catecholamine values were similar in the full-term and preterm lambs. After umbilical cord cutting there was a marked increase in circulating norepinephrine (NE) and epinephrine (E) in both full-term and preterm animals. The preterm animals exhibited a delayed but exaggerated elevation of both NE and E relative to term animals. The peak preterm value for NE (3.8 +/- 1.2 ng/ml) occurred at 60 min and exceeded the peak NE value 1.2 ng/ml observed at 15 min in full-term animals. The peak E concentration in preterm animals was over 9 ng/ml between 2 and 3 h of age, whereas full-term animals reached a peak value of 1.1 ng/ml at 5 min. Heart rate and blood pressure rose abruptly to peak values by 5-15 min in full-term animals. Changes in heart rate and mean arterial pressure were less profound and more gradual in preterm animals. Full-term animals also demonstrated a five-to sevenfold increase in plasma free fatty acids, whereas concentrations in preterm animals increased only two- to threefold. There was a similarly blunted response in blood glucose in preterm animals. The catecholamine surge at birth may be an important adaptive phenomenon with physiological implications.

The distribution and ontogeny of tissue prolyl endopeptidase and pyroglutamyl peptidase I activities were studied in the rat from the 7th day before birth to adulthood. While low levels of prolyl endopeptidase activity were demonstrable in many fetal tissues, activity in brain cortex, hypothalamus, lung, and kidney increased dramatically during the 2 wk after birth, gradually returning to adult levels. In adult rats, levels of tissue prolyl endopeptidase activity were highest in kidney, when compared with the intermediate levels in brain cortex, hypothalamus, and liver. Pyroglutamyl peptidase activity was widely distributed in adult rat tissues with high levels in kidney and liver that exceeded intermediate levels in brain cortex and hypothalamus. Pyroglutamyl peptidase activities in fetal gut, brain, and lung tissue were elevated above adult values. In contrast to the development changes in prolyl endopeptidase activities, pyroglutamyl peptidase activity remained elevated above adult levels only during the first week of life. These results indicate that both prolyl endopeptidase and pyroglutamyl peptidase activities in the rat are developmentally regulated.

The ontogenesis of hypothalamic and extrahypothalamic thyrotropin-releasing hormone (TRH) and the effect of altered thyroid status on tissue TRH levels were studied in fetal sheep. At 62 days gestation (term = 145 days) TRH was detectable in serum and in hypothalamic, placental, and pancreatic tissues; pancreatic, placental, and serum levels exceeded hypothalamic levels two- to fivefold. Analysis of tissues obtained from 88-day gestation fetuses were comparable: TRH levels in placenta (54 +/- 15 pg/mg tissue protein), pancreas (34 +/- 5 pg/mg protein), and serum (93 +/- 9 pg/ml) exceeded those in hypothalamic extracts (15 +/- 9 pg/mg protein). By 120 days gestation, TRH values in the hypothalamus (610 +/- 52 pg/mg protein) exceeded those in extrahypothalamic sites; values were comparable at 140 days gestation. Fetal thyroidectomy resulted in a 2-fold elevation of hypothalamic TRH concentrations (1,030 +/- 139 vs. 522 +/- 29 pg/mg protein) and 2 to 20-fold elevations of TRH in the placenta (147 +/- 23 vs. 42 +/- 8 pg/mg protein), pancreas (195 +/- 11 vs. 29 +/- 7 pg/mg protein), duodenum (363 +/- 97 vs. 29 +/- 7 pg/mg protein), and serum (2,563 +/- 212 vs. 131 +/- 16 pg/ml). 3, 5, 3'-Triiodothyronine (T3) infusion in thyroidectomized fetuses resulted in elevated serum T3 values (480 +/- 80 ng/dl) and suppressed hypothalamic TRH (249 +/- 68 vs. 522 +/- 29 pg/mg protein) and serum TRH concentrations (30 +/- 4 vs. 131 +/- 156 pg/ml). Placental, pancreatic, and duodenal TRH concentrations in thyroidectomized T3-infused animals were below the level of detection of the assay (5 pg/mg tissue protein).(ABSTRACT TRUNCATED AT 250 WORDS)