Heterogeneity of adrenocorticotrophin in the pituitary gland and plasma during the perinatal period.

Abstract

Three immunoreactive forms of ACTH are characterized by their apparent molecular weight (MW) and bioactivity when acid extracts of the anterior or of the neurointermediate lobe of fetal and newborn rat pituitary glands are subjected to gel filtration on Sephadex G50 fine columns. The "big" ACTH form which shows an apparent MW close to 44 000 hardly stimulates the in vitro release of corticosterone by perifused fetal adrenals. In contrast, the "intermediate" (MW: congruent to 13 000) and "little" (MW: congruent to 4 500) forms show high biological activity by eliciting corticosterone secretion which is log-dose-dependent. During the perinatal period, the relative proportions between these different molecular forms of ACTH change in both the anterior and neurointermediate lobes. "Big" ACTH is the main form in the neurointermediate lobe of the fetal rat pituitary. After birth, the "big" ACTH/total ACTH ratio regularly decreases until postpartum week 4; it is not very different then from that of pregnant adult females. The three immunoreactive forms of ACTH are present in the anterior lobe throughout the perinatal period. The gradual increase of the "intermediate" and "little" forms is accompanied by a correlative decrease in the "big" form. The anterior lobes of 17, 19 and 21-day old fetuses, stimulated in vitro by an acid extract of adult hypothalamus, release the three immunoreactive forms of ACTH in the same proportions as those observed in corresponding extracts of anterior lobes. On days 17, 19 and 21 of gestation, fetal plasma contains all the immunoreactive forms of ACTH previously observed in pituitary glands. The proportion of the "little" ACTH form gradually increases, whereas that of the "big" form decreases as gestation progresses. At term, the relative proportion of "little" ACTH is greater in the plasma than in the fetal pituitary. Controlled trypsic digestion of pituitary "big" ACTH results in a conversion to the "intermediate" and "little" immunoreactive forms. When "intermediate" ACTH is submitted to tryptic digestion under the same conditions, there is continuous loss of immunoreactivity but no change of hormonal form. These findings strengthen the hypothesis that "big" ACTH is a precursor of "intermediate" and "little" ACTH; in contrast, the "intermediate" form is not a precursor of the "little" one. The high molecular-weight form of ACTH might be converted endogenously into lower MW forms in the fetal circulation at term as well as in newborns. In fetal plasma, immunoreactive ACTH levels reach peak values on day 19 of gestation and decrease thereafter until day 21.(ABSTRACT TRUNCATED AT 400 WORDS)