Susan L. Jenkins

A comparative study of cardiovascular, endocrine and behavioural effects of betamethasone and dexamethasone administration to fetal sheep.

1. Chronically instrumented, late‐gestation fetal sheep were prepared to: (1) characterize cardiovascular, endocrine and behavioural effects of fetal treatment with clinical doses of betamethasone and dexamethasone; (2) define specific differences, if any, in the actions of betamethasone and dexamethasone of measured fetal responses; and (3) assess the contribution of changes in peripheral vascular resistance to the glucocorticoid‐induced hypertension. 2. Following baseline, either saline (n = 9), betamethasone (n = 9), or dexamethasone (n = 6) was infused for 48 h in fetal sheep commencing at 125 days of gestation. A pronounced increase in fetal blood pressure occurred following both betamethasone and dexamethasone treatment. The nature and magnitude of this increase was similar following treatment with either glucocorticoid. 3. To address possible mechanisms contributing to the glucocorticoid‐induced fetal hypertension, fetal plasma catecholamine levels and changes in fetal femoral haemodynamics were assessed following fetal glucocorticoid treatment. A fall in fetal plasma noradrenaline and adrenaline concentrations occurred during betamethasone and dexamethasone treatment. In contrast, a progressive femoral vasoconstriction occurred during betamethasone treatment. 4. A modest fall in the incidence of fetal breathing movements occurred during fetal treatment with either betamethasone or dexamethasone. The magnitude of this reduction was similar with treatment of either glucocorticoid. The fall in fetal breathing during betamethasone and dexamethasone treatment was not associated with a fall in the incidence of fetal low voltage electrocortical activity. 5. Our results indicate that prenatal betamethasone and dexamethasone treatment of late‐gestation fetal sheep, in doses similar to those employed clinically, is associated with fetal cardiovascular, endocrine and behavioural effects. Both betamethasone and dexamethasone induce similar increases in fetal blood pressure and similar falls in the incidence of fetal breathing movements. The pronounced betamethasone‐induced fetal hypertension is associated with an increase in fetal femoral vascular resistance.

Alteration of 24-hour rhythms in myometrial activity in the chronically catheterized pregnant rhesus monkey after a 6-hour shift in the light-dark cycle

We determined the effect of a 6-hour phase shift in the light-dark cycle on the 24-hour rhythm of myometrial activity with 15 chronically catheterized pregnant rhesus monkeys during the last third of gestation. Monkeys were housed indoors in constant temperature on a 14-hour-light/10-hour-dark photoperiod in two groups based on the time the lights were turned on (group A lights on at 6 AM and group B lights on at midnight). The power spectra were calculated for periods of 512 readings (1.138 hours) starting at the time the lights were turned on for continuous periods of 25.03 hours of data showing well-developed contraction-type activity at any time during that period. The power spectra data for contractures and contractions were analyzed separately from myometrial electromyographic data. During the 14 hours of light, myometrial activity was primarily composed of contractures. In all experimental animals the switch from contractures to contractions occurred around the time the lights were turned off. The proportion of contraction-type activity in each 1.138-hour analysis interval expressed as a percentage of the total contraction power for the whole 25.03-hour analysis period for all monkeys increased around the time the lights were turned off in both groups. The increase in contractions was observed 12 to 15 hours after the lights were turned on. No systematic change in the proportion of contracture activity was observed. Peak contraction activity was 22.6 +/- 0.60 hours (16.6 hours after lights on), and was at 18.3 +/- 1.4 hours (18.31 hours after lights on) in groups A and B, respectively. This difference was statistically significant (22.6 +/- 0.6 vs 18.3 +/- 1.4 hours, p less than 0.05). Seven of eight monkeys in group A and six of seven in group B had switched from contractures to contractions before lights were turned off. We have confirmed a 24-hour rhythm in myometrial activity in the pregnant rhesus monkey and provided new evidence to support the endogenous nature of this rhythm and its direct relationship to the light-dark cycle.

Opposing Effects of Androgen and Estrogen on Pituitary-Adrenal Function in Nonpregnant Primates

Abstract Maternal administration of androstenedione produces a sustained fall in maternal plasma adrenocorticotropic hormone (ACTH) concentrations in the pregnant nonhuman primate. We hypothesize a negative feedback influence on the maternal hypothalamo-pituitary-adrenal (HPA) axis by androgens in primates. This may reflect an important maternal adaptation during pregnancy in primates preventing premature induction of labor by maternal stress. However, androstenedione is precursor for placental estradiol-17β synthesis, and infusion of androstenedione into pregnant primates elevates maternal plasma estradiol-17β to term concentrations. Thus, it could be argued that 1) the effects attributed to androstenedione on the maternal HPA axis are mediated by estrogen rather than by androgen and 2) the negative influence of androgens may be on placental ACTH rather than, or in addition to, pituitary ACTH. To discriminate between androgenic and estrogenic effects of androstenedione on pituitary and/or placental ACTH function in primates we measured plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations in nonpregnant baboons after treatment with either androstenedione or estradiol-17β. Nine female baboons were studied between 14 and 22 days postpartum prior to estrous cycling. After 2 days of baseline, a continuous i.v. infusion of androstenedione (1.5 mg/kg per h in 10% intralipid, IL) was started at 0900 h and maintained for 9 days in 3 baboons. A similar protocol was carried out in another 3 baboons that received a continuous i.v. infusion of estradiol-17β (10 μg/kg per h in 10% IL) instead of androstenedione. Three additional baboons received continuous i.v. IL vehicle alone and served as controls. Arterial blood samples (0.5 ml) for measurement of plasma hormones were taken during baseline and after 1, 3, 5, 7, and 9 days of infusion. Baseline plasma ACTH, DHEAS, and cortisol concentrations were similar among all groups. Plasma ACTH did not change during IL, increased following estradiol-17β, and fell during androstenedione treatment. Accordingly, plasma cortisol and DHEAS concentrations were also unaltered by IL, and both steroids increased during estradiol-17β treatment. In contrast, plasma cortisol and DHEAS remained unaltered from baseline during androstenedione treatment, despite the fall in plasma ACTH measured at this time. These data in the nonpregnant baboon 1) are consistent with negative feedback on pituitary ACTH by androgens and 2) demonstrate a positive influence on pituitary-adrenal function by estrogen in primates.

Fetal growth in the baboon during the second half of pregnancy

The normal growth profile of critical fetal organs through the last third of gestation has not been documented in detail in human fetuses or the fetus of any nonhuman primate species. Recent epidemiological studies in human pregnancy suggest that fetal growth plays a major role in the programming of life‐long health by modifying cardiovascular, pancreatic, brain, and liver growth. The present study aimed to produce a detailed database of individual organ growth in the fetal baboon in late gestation. Fetal organ weights were obtained from 43 baboon fetuses between 121 and 177 days of gestation. Various organs (brain, heart, kidney, femur, intestines, and spinal cord) showed no sign of slowed growth in late gestation while growth of others (lung, liver, stomach, and bladder) accelerated in late gestation. The fetal adrenal and thymus showed a decrease in growth rate over the final 20 and 10 days of gestation respectively. These observations provide a database that will permit analysis of factors responsible for regulation of normal and altered fetal organ development in this important experimental species.