Hormonal Control of Labour Flashcards
Antenatal means
period before woman is in labour
During the antenatal phase…
Myometrium (the smooth muscle of the uterus) = Quiescent
It must not contract until time of birth. If it contracts before it is called preterm labour. If it remains quiescent then it leads to post term labour. Labour must happen at term = 40 weeks. (37-42 weeks)
Cervix (neck of the womb) = Closed
Membranes (which surround the baby, the amniotic sac) = Intact
Interpartum means..
period when labour begins
During the interpartum phase..
Myometrium = Contractile
If the myometrium contracts and relaxes the baby will never be born, if the uterus contracts and then relaxes the baby will go back in as the volume has to remain constant. So what must happen is that there has to be a permanent shortening of the muscle fibre length, this is called retraction. So, when the myometrium contracts it shortens, but it does not come back to its original length when it relaxes, it retracts. So there is contraction and retraction.
Cervix = Open
This is a passive process, the cervix is yielding to uterine contractions. But changes must happen in the cervix to facilitate this. So the cervix opens as a result of contractions from the uterus.
Membranes = Ruptured
They are ruptured as the process of labour is enhanced by breaking of the membranes. It is the most effective way of starting labour. BUT there is a problem that it is non reversable once the membrane is broken.
actin/myosin interactions
There is coupling of actin and myosin which leads to binding, bending of the head, so the muscle fibre length decreases. This is dependant of intracellular calcium. The calcium is then taken back for the muscles to relax, its an energy dependant process.
When the uterus is contracting in labour there is progressive effacement of the cervix:
The cervix has an internal os and an external os, there is a length to the cervical canal (left)
Nearer labour there is no length of the cervix, you cannot differentiate the internal os from the external os.
Percentage decrease in the length of the cervix = EFFACEMENT -the cervix stretches and gets thinner.
This often happens before labour begins. As labour nears, the cervix may start to thin or stretch (efface) and open (dilate). This prepares the cervix for the baby to pass through the birth canal.
SO… Once the cervix becomes very thin it will start to open in response to contractions of the uterus.
this happens under the control of several hormones
Why is a gradient of contraction important?
If the uterus contracts from all sides equally, the baby will never be born. So there as to be a gradient of contraction. The top of the uterus must contract first and stronger and for a longer period of time in order for the baby to be pushed down. This is called a triple descending gradient.
Quiescence phase- antepartum phase
What is responsible for keeping the uterus in a quiescence phase?
Progesterone
PGI2 – Prostacyclin (a prostaglandin)
Relaxin – relaxes the uterus
Parathyroid hormone-related peptide(PTHrP)
Calcitonin gene-related peptide, vaso-active intestinal peptide
Nitric oxide (NO) – smooth muscle relaxant, also acts in blood vessels.
How do the factors responsible for keeping the uterus in a quiescence phase work?
All these lead to increased intracellular (cAMP) or (cGMP) which inhibit the release of intracellular calcium for myometrial contractility.
So by inhibiting the intracellular release of calcium it will downregulate the contractile properties of the myometrium.
Activation Phase
When it is time to go into labour there is an activation/preparatory phase. Before actual labour starts, the environment must be right.
Duration of human pregnancy is 40 weeks from the last menstrual period.
Gestational age = menstrual age
It is NOT the age of conception. We do not know when this occurred, so all calculations are from the first day of the last menstrual period.
What ensures the right environment for activation phase?
Rise in estrogen and CRH (corticotropin releasing hormone – secreted by the brain)
Mechanical stretch
One theory is that when there is enough stretch in the uterus, then it is time to give birth. We know that when the stretching is too much, then labour starts to come early eg with twins.
There is up-regulation of a panel of genes required for contractions: Connexin 43, prostaglandin and oxytocin receptors (OTRs)
These genes control the synthesis of prostaglandins – prostaglandisn are stimulants of the uterus and oxytocin receptors.
Oxytocin is a hormone secreted by the pituitary, its function is to stimulate contractions of the uterus.
Stimulation Phase
When the process of preparation is completed, actual labour begins
Hormones involved in stimulation phase?
Prostaglandins
Prostaglandins form the final common pathway for labour.
Oxytocin
Hormone produced by the posterior pituitary that stimulate uterine contractions.
CRH
Increased synthesis of cytokines
Cytokines are proinflammatory substances, many processes of labour are similar to inflammation.]
Hormonal changes during initiation of labour?
Functional Progesterone withdrawal
If you measure progesterone levels during pregnancy they increase and the plateau. When somone goes into labour, the level of progesterone does onot change before labour begins.
Increased Estrogen bio-availability
Estrogen and progesterone are competing hormones, the antagonise each other, they reverse the action of each other. So there will be increased estrogen bio-availability, reducing the effects of prostaglandins on the body.
CRH and neuro-endocrine mediators
Increased responsiveness of the myometrium to prostaglandins and oxytocin
So not only is ocytocin secreted, but the responsiveness is also increased by increasing the concentration of receptors
Exact mechanisms of the initiation of labour is uncertain but believed to involve:
Progesterone
As it keeps the uterus quiescent
Oestrogen
It is antagonistic to progesterone action
Oxytocin
Is used to start contraction, if someone is not contracting well can give oxytocin
Relaxin
Corticotrophin-releasing hormone / fetal cortisol
Nitric oxide
As it keeps the uterus quiescent
Prostaglandins
Are also used as medicines to start labour
Inflammatory cytokines
Sheep are used to study pregnancy, found that infusing sheep with corticosteroids it starts labour off. But this did not work in humans
Progesterone profile
Progesterone is one of the main hormones of pregnancy
Produced by corpus luteum in early pregnancy and the placenta later on
Cholesterol is converted to Progesterone by the action of P450scc and 3βHSD
Wha happens to prog levels during myometrial contractility?
decreases
effect of prog on gap junction formation
Inhibits myometrial gap junction formation
effect of prog on NO synthetase?
Stimulates uterine NO synthetase
effect of prof on contractility
Stimulates cAMP and sequesters intracellular calcium in the sarcoplasmic reticulum (SR)
This inhibits contractility
effect of prog on prostaglandin production
Down-regulates prostaglandin production, development of calcium channels and oxytocin receptors, stopping the uterus from contracting.
effect of prog on cervix
inhibits collagenolysis in the cervix by increasing tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)
The cervix becomes shorter, but is should also become softer and more pliable for opening up. Progesterone stops this from happening.
inhibitory effects of progesterone
Prostaglandins synthesis
CRF secretion
Interleukin synthesis
Estrogen receptor expression
Oxytocin receptors affinity
Stimulatory effects of progesterone
Prostaglandins degradation
PTH-rp synthesis (Parathyroid hormone-related protein)
CGRP secretion - Calcitonin Gene-Related Peptide (is a vasodilator)
CGRP and AM (Adrenomedullin) receptor expression
what causes changes in prog activity?
In most species, progesterone levels fall pre-labour
This does not occur in humans
However there is changes to different progesterone receptors:
upregulation of PR-A (pro-inflammatory receptor),
and suppression of PR-B (anti-inflammatory receptor) receptor activity, This results resulting in “functional” progesterone withdrawal. So levels of progesterone remain the same but receptors change.
how does prog make contractility conditions suitable?
Increased PR-A/PR-B ratio is linked with activation of nuclear factor kappaB (NF-kB) in the myometrium
NF-kB increases expression of COX-2 and various pro- inflammatory cytokines (e.g. IL-8 and IL-1b), which cause cervical ripening and up-regulate oxytocin receptor expression in the myometrium
SO… it is making the environment favourable for action of substances that will contract the uterus.
oestrogen
Estrogen is essential for uterine development & function
The placenta is the primary source
