4/11 Endocrinology of Pregnancy Flashcards
This was a horrible lecture and there are no notes... I will get back to it later to clarify some things!
What are the sources of hormones during pregnancy? (both mom and kiddo)?
Mother: maternal endocrine glands
Placental synctiotrophoblast = pituitary-like.
Placental cytotrophoblast = hypothalmus-like
Fetus: hormone production develops as the fetus grows: HPA influences fetal adrenals and fetal testes. Adrenals produce steroids essential for normal pregnancy
Pregnancy measured from what timepoint?
hCG detected in what body fluid? how early can it be detected?
- Pregnancy measured from first day of last menstrual cycle
- hCG detected by serum or urine
- Detectable in 6-8 cell blastomere in vitro after 2 days
in 6 d blastocyst in culture
8-10 d post-conception in maternal serum
What are the roles of hCG in early pregnancy?
Primary function = maintenance of the corpus luteum.
Stimulates adrenal and placental steroidogenesis. Stimulates fetal testes in males to induce internal virilization.
Also is immunosuppressive of maternal lymphocyte function.
Later, the placenta makes more progesterone and estrogen, and there is less hCG made.
How much should hCG increase in early pregnancy?
What are the normal values?
Should increase by at least 66% every 48h in early pregnancy (first 7-8 weeks)
Normal maternal levels vary widely: a single value is not helpful, have to watch levels change over time.
How can hCG levels tell you if this is a normal or abnormal pregnancy?
Abnormal (ectopic or molar) –> hCG would be HIGH
What can hCG levels tell you about imaging of the pregnancy?
hCG levels help you know when you should be able to see the pregnancy with ultrasound (ie, should be able to see fetal heart at hCG of 17,000)
Also, hCG will be significantly higher with multiples (twins, trips) due to more placenta
What are the functions of estrogen during pregnancy?
- Increased uterine blood flow (20% of your blood flows through uterus per minute w preg -> can bleed out quickly!)
- Changes to blood, skin, breast development, respiration, GI, and carb metabolism
What are the functions of progesterone during pregnancy?
- Decidual reaction (changes in endometrium of the uterus that prepare it for implantation of a fertilized zygote)
- Decreased myometrial contractility
- Increase stretchiness of the uterine muscle
- Breast development
Progesterone: sources & levels throughout pregnancy?
- First 6-10 weeks: corpus luteum = main producer
- Transient decrease after 8-10 weeks due to transition in production from CL to placenta.
Estrogen: what is the primary estrogen type of pregnancy?
How do its circulating levels compare with levels of other estrogens?
Primary estrogen of pregnancy = Estriol
Circulating levels of estriol < estradiol due to rapid clearance of estriol
What is the molecule from which both progesterone and estrogen originate?
Cholesterol
At first glance, this is a terrible picture. But actually it’s sort of helpful.
Maroon = gonadotropins
Yellow = Progesterone
Blue = estrogen
What initially makes gonadotropins/what happens as pregnancy continues?
Same for progesterone and estrogen.
Gonadotropins (maroon): initially made by placenta (it appears) then production drops off with advanced gestation
Progesterone (yellow): initially made by ovary, then by ovary + placenta, then primarily by placenta
Estrogen (blue): initially made by ovary, then by ovary + placenta, then primarily by placenta
Three types of estrogen? where does each come from?
what is the relative potency?
(from FA)
Estradiol: from ovary as 17beta-estradiol
Estrone: from adipose tissue
Estriol: from placenta
Potency: estradiol > estrone > estriol
When is aneupolidy screening offered?
what does it test for?
Offered during the second trimester at approx 15-21 weeks’ gestation
Tests: “Quad screen”
alpha fetoprotein (AFP)
hCG
Estriol
inhibin A (dIA)
Quad screen hormones: where does each come from?
(estriol, hCG, inhibin, AFP)
estriol: syncytiotrophoblast
hCG: syncytiotrophoblast
inhibin: cytotrophoblast
AFP: fetal liver
syncytiotrophoblast v cytotrophoblast?
Both are layers of the placenta.
cytotrophoblast = closer to mom’s side (inner layer of chorionic villi)
syncytiotrophoblast = external to cytotrophoblast. (outer layer of chorionic villi)
What is the first biochemical marker for fetal Trisomy 21?
Low AFP levels
If a fetus has Trisomy 21, what will be the relative levels of AFP, estriol, hCG, and inhibin A?
Remember then in alpha order:
AFP and estriol are lower
hCG and inhibin A (dIA) are higher
if a fetus has Trisomy 18, what are the relative levels of AFP, estriol, hCG, and inhibin-A?
All are lower than normal
Other placental hormones: what are the categories?
Pituitary-like: hCG (similar to TSH); placental ACTH (similar to pituitary ACTH)
Hypothalamic releasing hormone-like: GnRH, TRH, CRH, CHRH, somatostatin
Endorphin-like: beta-endorphin and beta-lipotropin
What is the role of Prostaglandins on the myometrium?
- Stimulate contractility
- when progesterone is elevated, response of uterine tonicity to PGE2 and PGF2a is heightened
- at term, these PGs increase cyclic uterine contractions, leading to a role for PGs in labor
- PGs augment uterine responsiveness to oxytocin
What is the effect of prostaglandins on the cervix?
PGE2 –> cervical ripening. remodeling of the collagen matrix: makes it squishy/floppy when needed for childbirth
aka “cervical ripening”
What is the effect of Prostaglandins on the fetus?
- Prevent closure of the ductus arteriosus
- PG inhibitors induce early closure of the ductus arteriosus
(therefore use PG inhibitors for preventing preterm labor with extreme caution)
Two clinical uses of Prostaglandins in pregnancy?
- mid-trimester termination of pregnancy (may be given with RU 486)
- Cervical ripening/induction of labor
T/F
The role of maternal oxytocin in pregnancy and parturition remains unclear
T
T/F
Oxytocin receptors increase dramatically in number shortly before onset of labor
T
T/F
Initiation of parturition is a complex interplay between the fetus, placenta and maternal compartments
T
What occurs at an endocrine level to control parturition?
(starts with CRH and ACTH.. what happens from there?)
CRH and ACTH increase fetal adrenal production of DHEA-S.
DHEA-S is converted to estrogen by the placenta.
Progesterone levels remain high, but the ratio of Est to Progest is shifted.
Bottom line: CRH/ACTH -> DHEA-S -> estrogen
Besides increasing fetal production of DHEA-S, what does CRH do during parturition?
Also leads to production of fetal cortisol.
Cortisol feedback increases production of placental CRH.
Placental CRH increases uterine contractile response to oxytocin.
Increased fetal cortisol has what effect on the fetal lung?
how does it prepare the mom’s body for labor?
Cortisol -> fetal lung maturation (of Type 2 pneumocytes)
- > surfactant proteins, phospholipids
- > increased prostaglandins -> cervical ripening.
During parturition, what substances increase uterine irritability and contractility?
- Estrogen
- Oxytocin
- PGF-2alpha
During parturition, what substances suppress uterine irritability?
- Progesterone
- beta-2 agonists
Blood levels of what substance predict when labor will begin?
Maternal blood CRH!
CRH is produced by the placenta.
(that’s kind of cool; I didn’t know you could predict this with a blood test).
Parturition is a complex interplay of substances released from what 5 organs/structures?
Maternal pituitary
Maternal Adrenal glands
Placenta
Fetal adrenal glands
Fetal pituitary
