Oestrogen modulation with parturition in the human placenta

Abstract

An initial group of term (36-41 6/7 weeks), preterm (less than 36 weeks), and post-term (42 or more weeks) placentae were collected from women at delivery to determine the placental levels of important steroids and steroidogenic enzymes involved in the oestrogen synthesis pathway as a function of gestational age. A second group of placentae were obtained from women delivering at term before and after the onset of labour. Placentae were evaluated individually for cytosolic steroid hormone levels and microsomal steroidogenic enzyme activities. Oestradiol (E2), oestrone (E1), progesterone (P), and delta-4-androstenedione (A) were measured by radioimmunoassay in placental cytosols. Aromatase (AR), sulphatase (S), and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) activities were assayed in placental microsomes. Cytosolic concentrations of E1, E2, P, and A did not differ with respect to gestational age. Correspondingly, the microsomal enzyme activities of 3 beta HSD, S, and AR did not vary as a function of gestational age. However, when patients at term who were in labour prior to delivery were compared to those who were not, the placental cytosolic level of E1 was found to be threefold higher in the non-labouring group (4572 versus 1427 pg/mg cytosolic protein, P < 0.025). Additionally, microsomal aromatase activity was also significantly higher in the non-labouring patients (46 versus 19 pM/min/mg protein, P < 0.025), while the E2 to P ratio in the labouring patients was twice that of the non-labouring group, a difference which was significant at the P < 0.025 level (Wilcoxon rank sum test). These data suggest that at term, prior to labour, the placental production of E1 by AR is high, and that AR activity and E1 levels fall significantly after the onset of labour. Also, the placental cytosolic concentration of the more active oestrogen, E2, demonstrates stable to rising levels with a significant increase in E2/P after the onset of labour. We theorize that in the term pregnancy prior to labour, E1 may represent a large but relatively inactive intracellular oestrogen pool which is maintained by high AR activity, and may function to protect the pregnant local uterine environment from the more oxytocic effects of E2.