Question

Explain the initiation and regulation of labor contraction including all organs and hormones (and hormone-like molecules) that participate in the process. Describe the positive feedback mechanism of labor contractions. Why do you think the slow intravenous injection of synthetic oxytocin (Pitocin®) can be used to induce parturition (childbirth)? After childbirth, pituitary-derived oxytocin also triggers milk ejection. What is the initial stimulus for the secretion of oxytocin? What is the target cell type of oxytocin in the mammary gland? For parturition, which layer of the uterus does this hormone act on?

Answer 1

Ans :

Initiation and regulation of labour :

The exact sequence of events that leads to uterine contractions is still largely unknown. Some studies suggest mechanical stretch and hormones work together to initiate contractions in normal labor.However, due to the role of inflammation in preterm labor, other studies suggest that inflammatory mediators, such as cytokines and prostaglandins, initiate uterine contractions.

Mechanical stretch :

Mechanical stretch refers to tension on myometrial cells as the uterus distends. The physical stretching of the uterus causes an influx of ions, namely sodium and calcium, that changes the action potential across myometrial cells.This facilitates the onset of uterine contractions. The number of connexins (gap junctions) between myometrial cells increases just before labor, which allows coordinated muscle contraction. These cell-to-cell contacts are less abundant early in pregnancy, favoring uterine quiescence. It has also been suggested that uterine overdistention causes an "inflammatory pulse" that further activates myometrial contractility

Inflammatory mediators :

Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2.) Misoprostol is the synthetic version of PGE1, which although originally designed to prevent peptic ulcers, proved to have a dose-dependent effect on myometrial contractility.

PGE2 also plays a role in uterine contractions by activating EP1 and EP3 receptors on myometrial cells.The major physiological effect of PGE2 during labor, however, is activation of inflammatory mediators Il-8 and TNF-alpha that activate of collagenases and MMPs, leading to the ripening of the cervix.

3.Hormones :  The primary hormones involved include estrogen, progesterone, and oxytocin. Oxytocin is one of the most widely studied hormones involved in uterine contractions.

4.Positive feedback :

During labor, oxytocin is released from the posterior pituitary and exhibits positive feedback upon activation of receptors on myometrial cells. These receptors are rhodopsin class 1 G proteins that are coupled to phospholipase C (PLC), which then activates inositol triphosphate (IP3) and diacylglycerol (DAG.) Activated IP3 mobilizes calcium from the sarcoplasmic reticulum which then binds to myosin light chain kinases resulting in smooth muscle contraction.

It has also been suggested that calcium released from the sarcoplasmic reticulum within myometrial cells activates L-type calcium channels (voltage-gated) on the surface of the myometrial cell membrane, allowing a further influx of calcium ions that exert a positive inotropic effect on myometrial contractility

5. Synthetic oxytocin :

Synthetic oxytocin ( Syntocinon) stimulates uterine smooth muscle contractility and is widely used in the United States for labor induction, augmentation, and third stage management

6. Following childbirth, suckling triggers oxytocin release, which stimulates myoepithelial cells to squeeze milk from alveoli. Breast milk then drains toward the nipple pores to be consumed by the infant.

7. Myometrium