Hormones of Parturition Flashcards
List the four phases of parturition.
Quiescence, activation, stimulation and involution.
What is the term for a muscle cell?
A myocyte.
What does the cytoplasm of myocytes contain that helps them to contract?
Actin and myosin.
Muscle contraction is triggered by raised intracellular levels of what?
Calcium.
What are the five substances implicated in quiescence?
Progesterone, prostacyclin, relaxin, parathyroid hormone-related peptide, nitric oxide.
Progesterone decreases the expression of what?
Contraction related proteins (CAPs)
Progesterone prevents what from binding to its receptors?
Oxytocin.
What other hormone might progesterone compete with for the same binding sites?
Cortisol.
What does cAMP stand for?
Cyclic adenosine monophosphate.
What does cAMP do?
Uncouples gap junctions.
What two effects do prostacyclin, nitric oxide, relaxin and parathyroid hormone-related peptide have?
They increase cAMP and decrease intracellular calcium concentrations.
What are the two main substances implicated in activation?
Oestrogen and gap junction proteins.
What two things cause myometrial receptors and signalling pathways to change so that they respond to contractile stimuli?
The mechanical stretch of the uterus, and increased fetal HPA axis activity.
True or false: the fetus can manipulate progesterone : oestrogen ratios and thus precipitate uterine activity?
True.
What are the three zones of the fetal adrenal gland?
The outer adult zone, the fetal zone and the transitional zone.
What does the outer adult zone of the fetal adrenal gland produce?
Aldosterone.
What does the fetal zone of the fetal adrenal gland procude?
Dehydroepiandrosterone sulphate (DHEAS)
What does the transitional zone of the adrenal gland produce?
Cortisol.
DHEAS is the fetal adrenal precursor for the production of which hormone?
Oestrogen.
The production of DHEAS is controlled by what hormone?
Adrenocorticotrophic hormone (ACTH).
Where is ACTH released from?
The anterior pituitary gland.
What stimulates the release of ACTH from the anterior pituitary?
Hypothalamic corticotrophin-releasing hormone (CRH).
Where else can CRH be produced?
The placenta.
CRH activity is attenuated by what?
CRH-binding protein (CRH-BP).
Where is CRH-BP synthesised?
The liver, placenta and brain.
Describe what happens to CRH and CRH-BP levels towards the end of pregnancy.
Levels of CRH increase, whilst CRH-BP decreases. This results in an increased mount of physiologically free CRH.
How is the maternal HPA axis protected from overstimulation?
Maternal adrenal CRH receptors are down-regulated so the ACTH response to CRH is blunted.
Fetal stress (e.g. hypoxia) increases CRH. What physiological effect does this have?
CRH acts as a vasodilator in the placental vascular bed, increasing blood flow to the fetus.
Describe how a compromised fetus can precipitate labour.
Chronic fetal stress increases CRH levels. This increases fetal ACTH production, which increase DHEAS production in turn. Oestrogen synthesis is therefore increased, aiding myometrial activation.
CRH receptors can couple with what?
Different G-proteins.
For most of pregnancy, CRH is coupled to the G-protein involved in increasing what?
cAMP
Towards term, CRH couples with other G-protein pathways so it now activates what?
Phospholipase C (PLC)
What does PLC do?
It mobilises calcium from intracellular stores = increased myometrial activity.
What physiological effect does the cortisol produced the fetal adrenal gland have?
It matures the fetal organs in preparation for extrauterine life.
Maturing fetal lungs produce what?
Surfactant.
Inflammation in the fetal membranes and underlying myometrium amplifies signals leading to labour. What three substances cause this inflammation?
Surfactant proteins, phospholipids and pro-inflammatory cytokines.
Which hormone triggers the up-regulation of CAPs?
Oestrogen.
Give three CAPs.
Connexin 43, prostaglandins and oxytocin receptors.
Gap junctions are formed from what?
Bundles of proteins (connexins).
What do gap junctions allow?
The rapid transmission of signals and synchronisation of contractions.
Approximately how many gap junctions are present per myocyte towards term?
1000.
What causes a pre-labour rise in the amount of myometrial oxytocin receptors?
Uterine distension.
What three factors are implicated in stimulation?
Prostaglandins, oxytocin and CRH.
Give two examples of cytokines involved in cervical ripening?
Interleukin 1-beta and tumour necrosis factor.
What inflammatory-like changes occur that cause cervical ripening?
Increased synthesis of prostaglandins and cytokines cause an influx of macrophages and neutrophils.
What do macrophages and neutrophils do to the cervix?
They infiltrate the cervical tissue and produce enzymes, which digest extracellular matrix proteins.
Fill the blanks: ___ converts ___________ into prostaglandins.
Cyclooxgenase (COX) converts arachidonic acid into prostaglandins.
How short are prostaglandins half life?
Approximately 3 minutes.
Where do prostaglandins exert their influence?
At a local or subcellular level.
What three hormonal changes trigger the increased synthesis of prostaglandins?
Increased DHEAS production. Increased oestrogen production. Decreased progesterone.
Synthesis of prostaglandins is up-regulated by which substances?
Cortisol, oestradiol, CRH, interleukin 1-beta and tumour necrosis factor.
Where are prostaglandins produced?
In the fetal membranes, decidua, myometrium and cervix.
What does the chorion produce during pregnancy which inactivates prostaglandins?
Prostaglandin dehydrogenase (PGDH) - an enzyme.
In late pregnancy, PGDH decreases, causing an increase in which prostaglandin?
Prostaglandin E2 (PGE2).
What are the two most important prostaglandins in labour?
PGF2-alpha and PGE2.
What is metabolised by the myometrium to produce PGF2-alpha?
PGE2.
What inhibits PGE2 production during pregnancy, but favours its production in labour?
Relaxin.
Where is oxytocin synthesised and released from?
It is synthesised by the hypothalamus and released from the posterior pituitary gland.
At 32 weeks, how many times have the oxytocin receptors in the myometrium and decidua increased by?
They have increased 100 fold.
At term, how many times have the oxytocin receptors in the myometrium and decidua increased by?
They have increased 300 fold.
True or false: the fetal posterior pituitary also produces oxytocin during labour?
True.
Which substance helps to maintain uterine blood flow during labour?
Prostacyclin.
True or false: catecholamines inhibit uterine activity?
False: catecholamine both stimulate and inhibit uterine activity.
What effect does noradrenaline have during labour?
It increases uterine contractions (contributes to the fetal ejection reflex).
What effect does adrenaline have during labour?
It causes uterine relaxation, slowing labour.
