Mechanisms and Hormones of Parturition

• A decrease in progesterone receptor expression.
• A switch in the types of receptor isoforms present in the tissue.
• Local metabolism of progesterone within the uterine environment.

Increased Estrogen Bioavailability

As progesterone's inhibitory influence wanes, estrogen begins to dominate. Pregnancy is considered a hyperestrogenic state, with the placenta serving as the primary source of estrogen. Estrogen concentrations increase alongside gestational age and act to counteract the effects of progesterone.

Estrogen facilitates labor by promoting several critical myometrial changes:

• Increasing the number of prostaglandin receptors.
• Increasing the number of oxytocin receptors and stimulating oxytocin release.
• Increasing the expression of myometrial gap junctions, which allows for coordinated contractions.
• Up-regulating the enzymes necessary for muscle contractions.
• Promoting cervical ripening, the process that softens and prepares the cervix for dilation.

Myometrial Responsiveness and Contractile Stimuli

Once the hormonal environment has shifted, the myometrium becomes highly responsive to specific chemical signals that trigger contractions.

Oxytocin and Prostaglandins

Oxytocin and prostaglandins work in a powerful positive feedback loop to drive the labor process.

• Oxytocin: A polypeptide hormone produced by the maternal hypothalamus and secreted by the posterior pituitary. It directly stimulates uterine contractions and also signals the placenta and decidua to release prostaglandins.
• Prostaglandins: These are cyclic fatty acids (specifically $PGF_{2\alpha}$ and $PGE_2$) produced by the placenta and uterine tissue. They serve to stimulate uterine contractions, enhance the effects of oxytocin, and promote cervical ripening.

Uterine Stretch

Physical factors also play a role in the initiation of labor. As the fetus grows, the physical stretching of the uterine wall (uterine stretch) contributes to the mechanical signals that trigger the transition to active labor.

The HPA Axis and CRH Activation

The neuroendocrine system plays a vital role in amplifying the signals for birth through the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis.

Corticotrophin-releasing hormone (CRH) is a key neuropeptide in this process. It is produced by the hypothalamus (in both the maternal and fetal brains) and, significantly, by the placenta near term. CRH can be activated by stress and acts as a central component of the HPA axis.

The activation of the CRH-HPA axis leads to a cascade of events:

1. CRH stimulates the pituitary gland to secrete Adrenocorticotropic hormone (ACTH).
2. ACTH stimulates the adrenal glands to produce glucocorticoids (GC), such as cortisol.
3. These glucocorticoids further amplify uterine sensitivity by increasing estrogen production and prostaglandin synthesis.

Summary of Parturition Mechanisms

The initiation of labor is not the result of a single "trigger" but rather a convergence of multiple pathways: