Alterations in oxytocin prohormone processing during early development in the fetal sheep

Abstract

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.

Role of Carboxy-Extended Forms of Oxytocin in the Rat Uterus in the Process of Parturition1

“…Throughout late gestation, the predominant peptide products are the OTX forms. The predominance of OTX forms is similar to what is seen in the neurohypophyseal system in the fetal rat [8] and in the umbilical plasma in the ovine and human term fetus [9,10]. In adult animals, processing of OTX forms to mature amidated OT occurs much more efficiently in the rat neurohypophysis [8], and the predominant OT translation product is amidated OT.…”

“…In fetal sheep plasma, the concentrations of OTX forms are 35-fold higher than that of OT at two thirds of the way through gestation [9]. However, by term, the concentration of OTX has declined to one half, and OT has increased several-fold, suggesting a similar pattern of maturation.…”

Oxytocin as an Inducer of Cardiomyogenesis

“…Biochemical and recombinant DNA studies have demonstrated that it is synthesized as a non-glycosylated protein, which undergoes an initial endoproteolytic cleavage by the convertase magnolysin (EC 3.4.24.62) to OT-Gly-Lys-Arg (OT-GKR) (Brownstein et al, 1980;Burbach et al, 2001). Subsequent processing produces other OT extended molecules: OT-Gly-Lys (OT-GK) and OT-Gly (OT-G) (Burbach et al, 2001), all these forms are often referred to as OT-X (Morris et al, 1992). OT-G is converted by an -amidating enzyme to C-amidated nonapeptide.…”

“…In rats, enzymatic OT-X conversion to OT is almost complete in adulthood, but not in fetuses, which accumulate OT-X in the brain (Altstein et al, 1988a;Altstein & Gainer, 1988b. Similarly, the plasma OT-X elevation reported during early fetal development in sheep (Morris et al, 1992) is reduced in late gestation, when OT begins to predominate in the cbloodstream. We have recently shown that the OT-GKR is the main form in the fetal heart.…”

Oxytocin-Gly-Lys-Arg stimulates cardiomyogenesis by targeting cardiac side population cells

“…The ability to process the initial translation product through to mature OT is developmentally regulated and increases during late fetal and early neonatal development (Mitchell et al 1998). In fetal sheep plasma, the concentrations of extended forms of OT are 35-fold higher than that of OT (Morris et al 1992). Similarly, in human umbilical plasma, a higher concentration of OTextended forms than OT was reported (Mueller-Heubach et al 1995).…”