Parturition, commonly known as labor, is the physiological process of expelling the fetus and the placenta from the uterus. This transition is governed by a highly regulated sequence of hormonal changes that shift the uterus from quiet maintenance to intense, coordinated activity. The timing of this shift is controlled by an intricate conversation occurring between the maternal body, the placenta, and the developing fetus. Understanding which hormones initiate and drive this process provides insight into the mechanisms that ensure birth occurs at the optimal time.
Maintaining Pregnancy: The Role of Progesterone
Throughout the majority of the gestational period, the uterus remains in a resting state, largely due to the sustained influence of the hormone progesterone. This steroid hormone, produced first by the ovaries and later in large quantities by the placenta, is considered the primary factor in maintaining the pregnancy. Progesterone acts on the myometrium, the muscular layer of the uterus, to suppress contractility and promote a calm environment.
The hormone mediates this effect by hindering the expression of genes that code for contraction-associated proteins and inflammatory molecules. This action keeps the uterine muscle fibers relaxed and unresponsive to stimuli that might otherwise trigger premature contractions. Progesterone also helps maintain the integrity of the cervix, preventing it from softening or dilating too early in the pregnancy. For labor to begin, the uterus must first overcome this dominant, quieting effect of progesterone.
The Critical Shift: Estrogen and the Fetal Signal
The initiation of labor requires a functional mechanism to negate the progesterone-mediated block, allowing the uterus to become responsive to contractile signals. In humans, circulating progesterone levels do not drop significantly before labor, suggesting the switch is a “functional progesterone withdrawal” rather than a true reduction in hormone concentration. This functional withdrawal involves a change in the progesterone receptor types within the uterine tissue, which alters the way the muscle cells respond to the hormone.
Coordinating with this change is an increase in the influence of estrogen, which acts as the major preparatory hormone for the onset of labor. Estrogen promotes uterine sensitization by significantly increasing the number of receptors for oxytocin on the myometrial cells, making the uterus far more sensitive to this powerful contraction-inducing hormone. It also stimulates the local production of prostaglandins, which are necessary for both muscle contraction and cervical changes.
The timing mechanism for this shift is believed to originate from the fetus through the production of corticotropin-releasing hormone (CRH). This peptide hormone, produced by the placenta and the fetal brain, increases exponentially during the final weeks of pregnancy. CRH stimulates the fetal adrenal gland to produce a precursor steroid called dehydroepiandrosterone sulfate (DHEA-S). The placenta then converts this DHEA-S into a highly active form of estrogen known as estriol, driving the estrogen surge that prepares the uterus for action.
Hormones Driving Uterine Action: Oxytocin and Prostaglandins
Once the uterus has been sensitized by the functional decrease in progesterone effect and the rise in estrogen influence, the immediate physical work of labor is driven by two main effector hormones: oxytocin and prostaglandins. Oxytocin is a peptide hormone released from the maternal pituitary gland and is a potent stimulator of myometrial contractions. It acts on the now-abundant oxytocin receptors in the uterus, causing the synchronized, forceful contractions that define active labor.
The release of oxytocin is part of a positive feedback loop, where contractions and the pressure of the fetal head on the cervix stimulate the release of even more oxytocin. This increasing concentration and effect lead to contractions that become progressively stronger and more frequent. Prostaglandins, a group of lipid compounds, work alongside oxytocin and perform a dual function during labor.
Specifically, Prostaglandin E2 (PGE2) and Prostaglandin F2\(\alpha\) (PGF2\(\alpha\)) directly stimulate uterine muscle contractions. Their second role is promoting cervical ripening, the necessary process of softening, thinning, and opening the cervix. Prostaglandins achieve this by initiating biochemical changes in the cervical tissue’s collagen and extracellular matrix, ensuring the birth canal is ready for passage.
The Cascade: How These Hormones Work Together
The initiation of labor is a carefully orchestrated sequence of hormonal events that build upon one another in a cascade. The process begins with uterine quiescence sustained by the dominance of progesterone throughout gestation. This period of calm is a prerequisite for fetal development and growth.
As the fetus reaches maturity, the signal for labor begins with the exponential increase of fetal and placental CRH. This CRH acts as the initial trigger, setting the biological timing and stimulating the production of DHEA-S, which is converted to estriol in the placenta. This rise in estrogen promotes the functional withdrawal of progesterone action in the uterine muscle cells, simultaneously increasing the number of oxytocin receptors.
The sensitized uterus is now prepared for the final phase, initiated by the release of oxytocin and the local production of prostaglandins. Oxytocin drives the powerful, rhythmic contractions, while prostaglandins ensure the cervix softens and dilates and contribute to the contractile force. This entire sequence is characterized by positive feedback loops, such as the increasing oxytocin release and the CRH-estrogen cycle, which accelerate the process. This system ensures a synchronized transition to the active, self-sustaining process of birth.