Release of bioactive ACTH by perifused human placenta at early and late gestation

This study assessed whether bioactive ACTH is released by the human placenta during perifusion in vitro at early and late gestation. Human placental villous fragments from early (8-12 weeks) and late (38-40 weeks) gestation were perifused at a constant rate for 6.5 h. To assess ACTH-like bioactivity released by this tissue, the perifusion effluent was redirected through adjacent chambers containing freshly dispersed adrenocortical cells obtained from adult rats. Baseline secretion of corticosterone by these adrenocortical cells averaged 95 +/- 26 (S.E.M.) fmol/min, and this increased at least fivefold (P < 0.01, two-way ANOVA) in response to placental effluent at early and late gestation. The magnitude of this increase, expressed as a percentage of the maximal response to a subsequent stimulus with ACTH(1-24), was similar for placentas obtained at early (41 +/- 12% of maximal response) and late (42 +/- 17%) gestation. Immunoreactive (I)-ACTH was readily detectable in placental effluent from all preparations (5.5 +/- 2.3 fmol/min per g tissue), and there was no apparent difference with stage of gestation. To determine whether all of the ACTH-like bioactivity released by the placenta was attributable to I-ACTH, a second series of placental/adrenal perfusions was conducted. In these, I-ACTH was selectively removed from placental effluent by immunoneutralization, and the residual bioactivity measured. Immunoneutralization involved preincubation of placental effluent with ACTH antiserum (1:100), and preincubation with normal rabbit serum (NRS) served as a control.(ABSTRACT TRUNCATED AT 250 WORDS)