Mitchell B F, Fang X, Wong S
a Perinatal Research Centre, Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada T5H 3V9.
Biol Reprod. 1998 Dec;59(6):1321-7. doi: 10.1095/biolreprod59.6.1321.
The hypothalamic synthetic pathway of oxytocin (OT) involves the synthesis of carboxy-extended forms that serve as intermediate prohormones. We hypothesized that extended forms of OT are synthesized in the late-gestational rat uterus and that they compete for OT receptor binding. Parturition occurs only when the ratio of OT to its extended forms reaches a critical level. We have measured OT and its extended forms using two antisera, one recognizing OT and its extended forms, the other recognizing only mature amidated OT. Uterine tissue concentrations of extended forms of OT were 5- to 30-fold greater than those of OT, and both increased progressively and significantly through late gestation. The ratio of OT to its extended forms did not change significantly. Antagonists of estrogen or progesterone receptors reduced concentrations of extended forms by > 90% and of OT by 50%, though the estrogen antagonist significantly prolonged gestation and the progesterone antagonist induced preterm delivery. Using a muscle bath preparation, extended forms of OT were weak uterine stimulants and did not alter the OT concentration-response curves. Extended forms of OT were two to three orders of magnitude less able than OT to displace radiolabeled OT from late-gestational uterine binding sites. We conclude that uterine carboxy-extended OT prohormones are regulated in part by estrogen and progesterone. However, these extended forms of OT have little direct biological activity and do not compete with OT for receptor binding. Their role in the process of parturition may be confined to acting as substrates for OT synthesis.
催产素（OT）的下丘脑合成途径涉及羧基延伸形式的合成，这些形式作为中间前激素。我们假设OT的延伸形式在妊娠晚期大鼠子宫中合成，并且它们竞争OT受体结合。只有当OT与其延伸形式的比例达到临界水平时才会发生分娩。我们使用两种抗血清测量了OT及其延伸形式，一种识别OT及其延伸形式，另一种仅识别成熟的酰胺化OT。OT延伸形式的子宫组织浓度比OT高5至30倍，并且在妊娠晚期两者均逐渐且显著增加。OT与其延伸形式的比例没有显著变化。雌激素或孕激素受体拮抗剂使延伸形式的浓度降低>90%，使OT的浓度降低50%，尽管雌激素拮抗剂显著延长了妊娠期，而孕激素拮抗剂诱导了早产。使用肌肉浴制剂，OT的延伸形式是较弱的子宫刺激剂，并且不会改变OT浓度-反应曲线。OT的延伸形式从妊娠晚期子宫结合位点置换放射性标记OT的能力比OT低两到三个数量级。我们得出结论，子宫羧基延伸的OT前激素部分受雌激素和孕激素调节。然而，这些OT的延伸形式几乎没有直接的生物学活性，并且不与OT竞争受体结合。它们在分娩过程中的作用可能仅限于作为OT合成的底物。
