Hormonal Changes in Pregnancy Flashcards
What hormones are produced by the placenta?
Many incl. peptides, steroid hormones and monoamines
What is the action of leptin secreted by the placenta?
It stimulates production and uptake of fatty acids and amino acids across the placenta
Where does steroidogenesis take place in pregnancy?
3 compartments
1) Fetal - fetal adrenal glands produce some steroids which stimulate production of placental steroids
2) Maternal component - source of precursors, clearance of steroids
3) Placental
What steroid hormones does the placenta produce that go into the maternal circulation?
1) Progesterone
2) Oestrone
3) Oestradiol
4) Oestriol
What does the placenta take over from very soon after the start of pregnancy?
Takes over the corpus luteum to produce progesterone
What is progesterone?
A pro-gestational hormone - helps gestation continue
Why is progesterone given to people in IVF?
- To give people more in case they are deficient in it
- It stimulates the proliferation of cells around the embryo and the embryonic cells themselves early on in gestation
Do we know what starts labour in humans?
No
What is the action of the fetal adrenal gland?
1) Picks up pregnenolone from placenta
2) Converts it to dehydro-epiandrosterone (DHEA)
3) DHEA is converted to androstenedione in the placenta which is converted into oestrone and oestradiol and transported to the maternal circulation
4) DHEA is also converted to DHEA sulphate which is converted into 16-hydroxy-DHEAS in the fetus
5) This is converted to oestriol in the placenta which is transported to the maternal circulation
What is the effect of a problem in the fetal adrenal gland e.g. congenital malformation or genetic defect?
This will lead to poor pregnancy outcomes bc the fetus doesn’t produce the right hormones for production of placental and maternal steroid hormones
What is the role of oestrogens in pregnancy?
1) Stimulate synthesis of liver fatty acids and cholesterol
2) Cardiovascular adaption to pregnancy
3) Growth of uterus
4) ‘Priming’ of uterus for labour
5) Weak anti-insulin activity via enhanced cortisol
6) Onset of labour-relative vs fall in progesterone?
7) Cervical ripening
8) Stimulates RAAS
What happens to oestrogens in pregnancy?
They increase
How does the cardiovascular system adapt to pregnancy?
- CO increases but diastolic BP decreases to compensate
- Lots of vasodilation
What BP should you be concerned about in early pregnancy?
90 (systolic?)
How is the uterus primed for labour involving oestrogens?
- Myometrial cells become electrical connection, so they contract together (like the heart)
- Oestrogens change gap junctions
- Brexton-Hicks contractions are uncoordinated towards end of pregnancy
Why is RAAS stimulated in pregnancy?
- Stimulates the mother’s blood volume to increase
- System goes into overdrive in early pregnancy
- Mother retains sodium and water
What happens to progesterone in pregnancy?
It increases
Up until what day of pregnancy is progesterone produced by the corpus luteum?
Day 50-60 (then placenta takes over)
What is the role of progesterone in pregnancy?
1) Prepares and maintains the endometrium to allow implantation in the endometrium
2) Involved in parturition
3) Serves as a substrate for fetal adrenal gland production of glucocorticoids and mineralocorticoids (aldosterone)
4) Growth of mammary glands
5) Maintenance of pregnancy
6) Induces over-breathing and lowering of maternal CO2
7) Stimulates RAAS
8) May have a role in suppressing the maternal immunologic response to fetal antigens
Why would you want to suppress the maternal immunologic response to fetal antigens?
- To prevent maternal rejection of the trophoblast
- Don’t know why women don’t reject fetus as non-self
- Maybe miscarriage is due to placenta rejecting fetus as not self
How does progesterone maintain pregnancy?
- Inhibits uterine contractility
- Prevents ripening of cervix
How does progesterone affect the respiratory system?
- Induces over-breathing and lowering of maternal CO2 by stimulating the brain stem
- Pregnant women breathe more deeply
- This increases pO2 and decreases pCo2
What hormone is the basis for the pregnancy test?
Human chorionic gonadotropin (hCG)
Why is hCG pregnancy test only accurate in early pregnancy?
Bc after the first few weeks (8 weeks) hCG levels start to decrease
What other hormone may be use to indicate pregnancy that increases exponentially from 12 weeks (esp. after 20 weeks)?
Human placental lactogen (hPL)
What are the two functions of hCG?
1) Rescue and maintenance of functionleading to continued progesterone production of the corpus luteum
2) Stimulation of maternal thyroid activity (thyroid goes into overdrive)
Describe how hCG rescues and maintains function of corpus luteum leading to continued progesterone production
1) At ~ 8th day after ovulation/1 day after implantation, hCG takes over for the corpus luteum
2) Continued survival of the corpus luteum is totally dependent on hCG
3) Survival of the pregnancy is dependent on corpus luteum progesterone until 7th week of pregnancy
4) Luteal progesterone synthesis begins to decline at about 6 weeks despite continued and increasing hCG production
How does hCG stimulate maternal thyroid activity?
1) hCG binds to the TSH receptors of thyroid cells
2) LH-hCG receptor is also expressed in the thyroid
3) Therefore hCG stimulates thyroid activity via the LH-hCG and TSH receptors
What are the metabolic actions of hPL?
1) Maternal lipolysis and increased in maternal plasma free fatty acids
2) Anti-insulin or ‘diabetogenic’ action
3) Potent angiogenic hormone - formation of fetal vasculature
Why do you want maternal lipolysis and increased in maternal plasma free fatty acids?
Provides a source of energy for mental metabolism and fetal nutrition
Why do you want an anti-insulin or ‘diabetogenic’ action?
Increase (decrease?) in maternal insulin, favouring provision of mobilisable amino acids and fetal protein synthesis as well as glucose for transport to the fetus
What are some other important placental proteins?
1) PAPP-A (pregnancy-associated plasma protein-A) - proliferative role through IGFs
2) VEGF (vascular endothelial growth factor)
3) PIGF (placenta growth factor)
4) Leptin - normally satiety hormone, different in placenta
What do low levels of PIGF indicate?
- Good indicator of pre-eclampsia bc PIGF is a angiogenic factor
- Now being used a diagnostic indicator
- Direct measure of placental function
What happens to levels of PAPP-A, hPL and SP1 in pregnancy?
They increase
Why are maternal levels of leptin significantly higher than in non-pregnant women and that in the fetal circulation?
Leptin is secreted by both cytotrophoblast cells and syncytiotrophoblast
What is the effect of leptin in pregnancy?
1) Stimulates placental amino acid/fatty acid transport
2) Fetal leptin levels - correlated positively with fetal birthweight
3) Probably plays an important role in fetal development and growth
4) Pregnant women don’t stop eating and become leptin-resistant
What happens to maternal glucocorticoid and mineralocorticoid hormones in pregnancy?
They all increase
Which glucocorticoid and mineralocorticoid hormones increase in pregnancy?
- Cortisol
- Deoxycorticosterone (DOC)
- Aldosterone
What is the role of glucocorticoid and mineralocorticoid hormones in pregnancy?
1) Help glucose go across the placenta
2) Stimulate the increase in blood volume
What are 3 main hormones involved in pregnancy?
1) Progesterone
2) Oestrogen
3) Prostaglandins
What happens to LH and FSH in pregnancy and why?
- Undetectable during pregnancy
- Suppressed by high circulating levels of oestrogen and progesterone
What happens to GH in pregnancy and why?
- Total GH concentration increases
- Placental growth hormone production (assays cannot distinguish this from pituitary growth hormone)
What happens to ACTH in pregnancy and why?
- Total ACTH level increases by 2x after the first trimester
- Placental production of cortisol releasing factor (CRF) and ACTH, however pituitary ACTH secretion is unchanged
What happens to IGF-1 in pregnancy and why?
- Increases in normal pregnancy
- IGF-1 production stimulated by hPL
What happens to ADH in pregnancy and why?
- Reduction in circulating ADH
- Placental vasopressinase production
What happens to prolactin in pregnancy and why?
- Progressive increase throughout pregnancy
- Increased oestrogen stimulates pituitary prolactin release
- Prolactin synthesised by decidual tissue but only small amounts enter fetal or maternal circulation
Why should you not measure prolactin?
Bc it will increase anyway and not consistently
What happens to renin in pregnancy and why?
- Increase up to 4x by 20 weeks of gestation then plateau
- RAAS activation results from the fall in TPR and resulting afterload reduction, and therefore allows the expansion of plasma volume
What happens to aldosterone in pregnancy and why?
- Levels increase up to 3x in the first trimester and 10x in the third trimester
- Response to increased renin and angiotensin II
What happens to thyroid hormones in pregnancy?
1) 50% more thyroid hormone required
2) Increased iodine requirement
3) Increased T4 production leading to TSH suppression, esp. in first trimester
4) Upper end of normal range for free T3 and T4 reduced in later pregnancy
5) Higher levels of total T3 and T4
What does low TSH in pregnancy indicate?
Thyrotoxicosis (pregnancy related)
- Fine tremor
- Bruit
- Goitre
- Tachycardia
- Oogly eyes
What can hypothyroidism (increased TSH and low T4/3) esp. in early pregnancy lead to?
Problems with the fetus’ brain development
Why do the changes to thyroid hormones in pregnancy occur?
1) De-iodination in placenta and increase in thyroid binding globulin (TBG)
2) Increase renal iodine clearance and fetal iodine uptake
3) Structural similarity of TSH and hCG leading to hCG mediated stimulation of TSH receptors in thyroid tissue
4) Haemodilution
5) Increase in TBG
What happens to cortisol in pregnancy and why?
- Serum cortisol (reflection total cortisol) increased top to 3x
- Urinary 24h free cortisol (reflecting free cortisol only) increases
- Suppression by exogenous corticosteroid is blunted
- Increase in cortisol binding globulin, cortisol releasing hormone (CRH) and progesterone
Which hormones have no know change in reference range in pregnancy?
PTH and catecholamines (vitamin D reference ranges for normal pregnancy not established)
To summarise, what are the endocrine changes in pregnancy?
1) Increased progesterone and oestrogen
2) Placenta secretes relaxin, hPL and hCG
3) Thyroid hyperplasia
4) Transient hyperthyroidism
5) Insulin resistance
6) Increased cortisol secretion by adrenal glands
What hormone involved in pregnancy does the fetus produce?
Alpha-fetoprotein
What hormones involved in pregnancy does the mother produce?
1) Corpus luteal hormone
2) Relaxin
3) Decidual hormone
4) Prolactin IGFBP-1 human chorion gonadotropin pregnancy protein 14
