SUMMARY

1. The defence mechanisms of the body are predominantly functions of the reticulo-endothelial system (RES). Stimulation of the RES leads to increased body defence indicated by increased phagocytic activity, raised serum γ-globulin and increased protection of experimental animals against virulent infections. The strongest RES stimulants appear to be oestrogens, natural and synthetic.

2. In the mouse, 0·002 mg. diethylstilboestrol daily is sufficient to produce significant prolongation of survival time against infection.

3. RES activity varies at different stages of the oestrous cycle and of pregnancy in both the rat and the mouse. The stages where the activity is greatest correspond with those in the human subject when the output of oestrogens is increased.

4. The results suggest that oestrogen is the natural stimulant of body defence in both the male and female, the latter having high oestrogen levels when protection against infection is normally most needed.

5. RES stimulation does not rise in step with oestrogenicity, and oestrogenic compounds have two separate biological activities—one which stimulates the RES to raise body defence, and one which acts on the reproductive organs; these two activities are apparently unrelated, although shared by the same molecule.

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130–133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 ± 121%, n=5, P<0·05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74·4–81·1% and 58–65% respectively, P<0·05, n=5). Four ewes received Trilostane (25 mg i.v.), a 3β-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19·8 ± 8·0% and 39·5 ± 24·3% respectively, P<0·05). The incidence of fetal EOG activity increased from a pretreatment level of 26·8 ± 1·5 min/h to 30·3 ± 2·8 min/h at 1–6 h and to 35·0 ± 1·7 min/h (P<0·05) during the 7–12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1–6 h and 7–12 h after Trilostane treatment (19·5 ± 3·0 and 23·6 ± 5·5 min/h respectively, P<0·05) compared with pretreatment levels (11·2 ± 1·2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM.

Journal of Endocrinology (1997) 152, 379–386