Endocrinology of Pregnancy Flashcards
Functions of Placental and Maternal Hormones
Maintain the corpus luteum during the first 7-10 wks
Adjust maternal metabolism to provide nutrients to the fetus
Stimulate the maternal circulatory system to transport gases and nutrients to and from the growing fetus
Dampen uterine contractility
Prepare the maternal tissues for childbirth
Prepare the breasts for lactation
Hormones are intimately involved in the complex processes that lead to parturition
What are the major Hormonal Changes in Pregnancy- Endocrine System
Insulin sensitivity early-resistance later (GDM)
Earlier conversion to fatty acid metabolism due to decreased maternal glycogen stores from fetal-placental glucose demands–fasting ketones
Changes in thyroid hormone levels (hCG)
Increased iodine requirements (goiter, hypothyroid)
Changes in autoimmunity (PPT)
Estrogen induced pit growth (Sheehan’s)
What are the cardiovascular and hematologic changes in pregnancy?
30-50% increase in C.O. (decompensation in CAD, CHF, Marfan’s, valvular stenosis)
Decreased SVR leads to decreased BP; no change in pulm vasc resistance in pts with pulm htn
Increase in HR
30-40% increase in blood volume (anemia of pregnancy)
Respiratory/Acid Base Changes from Hormones in pregnancy
Increase in tidal volume, minute ventilation leads to resp alkalosis
Compensated metabolic acidosis leads to lower buffering capacity (earlier DKA)
Increase in O2 consumption
Nasal mucosal edema (stuffy nose, sinusitis)
Renal Changes in Pregnancy
40-60% increased GFR (clearance of iodine, drugs) leads to decreased BUN and Cr
Increased renal blood flow
Altered tubular function (glucosuria)
Decreased ureteral peristalsis (pyelo)
Lowered osmostat for vasopressin release and thirst (hyponatremia)
GI Changes in Pregnancy
Decreased LES (GERD, aspiration pneumonia)
Decreased stomach emptying, peristalsis (gastroparesis, delayed absorption, constipation)
Decreased GB emptying (cholestasis)
What are the polypeptide-releasing hormones from placenta?
CRH (20-fold increase at term)
GnRH (stims hCG)
GHRH
TRH
What are the most important polypeptide hormones from placenta?
hCG
hPL (hCS)
hPGH (hGH-V)
hCG
Maintains corpus luteum (especially progesterone) in early pregancy (PEAKS EARLY at 10 weeks)
Glycoprotein (39 kD)
Secreted by syncytiotrophoblast
Alpha common to LH, FSH, TSH
Regulates differentiation of cytotrophoblast to syncytiotrophoblast; controls trophoblastic invasion
Induces apoptosis of endometrial T-cells to promote immune survival of embryo
TSH activity at high levels
Stimulates fetal Leydig cells to produce fetal testosterone
May cause hyperemesis
Stimulates Relaxin leading to increased GFR/Renal blood flow and decreases SVR in rats; studies ongoing in humans
hPGH
Contributes to insulin resistance of pregnancy (peaks later)
Secreted by syncytiotrophoblast
Differs from pit GH by 13 aa
Not regulated by GHRH
Same avidity for receptor
Secreted tonically; replaces pit GH by ~20 wks
Does not cross placenta but regulates IGF-1
Decreased by glucose; increased by hypoglycemia
Potent somatogen
Lost during normal labor and 1 hr after placenta removal
CRH
Likely plays a role in partuition (peaks later)
Steroid Hormones from Placenta
Progesterone
Estrogen (up to 100-fold increase)
1,25-OH Vit D
Placental Anatomy (when develops)
Day 4, embryo differentiated into inner cell mass (fetus) and trophectoderm (placenta)
6-7 days—endometrial attachment of trophoblast
What are the 2 types of trophoblastic cell phenotypes
mononuclear Cytotrophoblast (early)
Syncytiotrophoblast (multinuclear layer on surface of villi; predominates later)
Syncytiotrophoblast
Major site of protein and steroid production
Hemochorioendothelial placentation
Directly bathed by maternal blood within intervillous space
Separated from fetal blood by several layers of tissue
Net transfer of steroids and polypeptide hormones to maternal blood is»_space;> fetus
What transfers across placenta?
More permeable to lipid soluble molecules
Hormones > 1200 Daltons have minimal access
Hormones actively metabolized by placenta:
- T4 to rT3 by Type III Monodeiodinase (protects baby to some degree from hyperthyroidism)
- Cortisol to Cortisone by 11-B hydroxysteroid dehydrogenase (why it’s relatively safe to give some steroids in pregnancy)
What are the similarities in structure among hCG and TSH, FSH, and LH
Same alpha subunit
In high levels, can stimulate TSH hormone receptors
hCG–Endocrine Clinical Correlates
hCG has TSH activity first trimester
hCG-induced hyperthyroidism with HG
Lack of hCG doubling 1st trim—missed Abortion
No gestational sac; hCG >1500 U/L-ectopic
No cardiac activity; hCG>9000-missed Abortion
Altered in placental insuff and trisomies: increased hCG in Down’s–decreased Trisomy 18
Human Placental Lactogen (hPL) or Human Chorionic Somatomamotropin hCS)
Participates in the metabolic adjustments that deliver nutrients tot he developing fetus (peaks later)
Secreted by syncytiotrophoblast
Secretion rate parallels placental weight
Detected at 5-10 days-peaks ~32 wks
Made in massive quantities
Originally thought to be insulin resistance hormone of pregnancy
Facilitates mobilization and utilization of FFAs for energy by increased lipolysis
Both insulin and anti-insulin effects
Stimulates insulin secretion
Weak GH activity and mainly a lactogen—Promotes growth of mammary tissue and stims prolactin
What is the major insulin resistance hormone of pregnancy? And why do we need that?
hPGH
Maternal insulin resistance necessary to shunt glucose and amino acids to fetus to ensure adequate growth
hPGH decreased in growth restricted fetuses
Women with pre-existing insulin resistance develop GDM due to further insulin resistance from placental hormones and inadequate insulin secretion
Progesterone
Steroid hormone
Critical to maintain pregnancy
Corpus luteum produces it prior to 8-11 wks
Biosynthesis dependent on number of LDL receptors on trophoblast plasma membrane
~85% enters maternal circulation
Functions of Progesterone
Promotes decidua formation
Substrate for synthesis of cortisol and aldosterone in the definitive zone of the fetal adrenal cortex
Inhibits uterine contractions
Modulates immune system (promotes Th2 ab and suppresses Th1 cell mediated response)
Stimulates minute ventilation
Smooth muscle relaxant (GI, uterus; GU)
Promotes lobular development in the breast; inhibits milk secretion
May contribute to decreased SVR
When do we give progesterone to pregnant women?
Given for luteal phase defects
Given to prevent preterm labor
Misoprostone
Progesterone antagonist
Abortifactant
How does progesterone affect the health of the mother?
Autoimmune ds may improve; worsens post-partum (MS, PPT, Grave’s)
Gastroparesis worsens; GERD, aspiration pneumonia
Ureteral relaxation results in urinary reflux, high risk of pyelonephritis
Estrogen in pregnancy (where does it come from and what are the effects it exerts)
Levels may increase ~100-fold
High levels of placental aromatase
DHEAS converted to estrogens by placenta
90% estradiol secreted into maternal circ
Stimulates growth of myometrium
Induces hypercoagulable state (increases clotting factors, fibrinogen)
Induces protein synthesis (increased SHBG, TBG, CBG)
Induces lactotrophs; Inhs Dopa leads to increased PRL but antagonizes PRL at level of breast
Peripheral vasodilation (decrease SVR, BP)
Increases C.O.
Inc mucosal edema (sinusitis, epistaxis)
Increased uterine blood flow and decreased resistance
Inc blood volume (anemia)
Inc renal perfusion and GFR (increased proteinuria)
Inc TG synthesis
Increases Pit size and vasculature
What is primarily responsible for the hypercoagulable state of pregnancy? What is the increased risk for thrombosis?
5-10 X risk of thrombosis in pregnancy
Estrogen causes:
Stasis (venous flow decreases by 50% by 3rd trim)
Vascular Damage (vaginal del or C-section)
Hypercoagulability: increased factors V, VIII, vWF, fibrinogen increased resistance APC (40%) increased PAI-1 and PAI-2 decreased Prot S Increase in D-dimers and TAT complexes
Risk back to baseline by 6 wks PP
What is the effect of estrogen-containing OCPs on lactation?
May inhibit it!
Pancreatitis in pregnancy
Estrogen induced hypertriglyceridemia can cause pancreatitis
What is the leading cause of maternal mortality in US and UK?
Thromboembolism
PE’s account for 15-20% of pregnancy-related deaths in US
Relative risk of VTE 10X non-pregnant state–1/1,000 vs 1/10,000
Sheehan’s syndrome
Estrogen causes pit size to increase;
prolactin macroadenomas may enlarge
pit at risk for ischemia
