Endocrinology of Pregnancy and Parturition

Question 1

Compare and contrast lipid and protein hormones in terms of

• solubility
• site of receptors
• mechanism of action
• examples

Answer 1

Lipid-Based Hormones 
- hydrophobic
- receptors in cytoplasm/nucleus 
- MoA = induces gene transcription and translation 
- e.g. 
Steroids: oestrogens, progesterone, crotisol, androgens 
Protein Hormones 
- hydrophilic 
- receptors in cell membrane 
- MoA = initiates second messenger intracellular signalling mechanisms sich as cAMP
 - e.g. 
Gonadotrophins: FSH, LH, hCG
Somatomammotrophic: prolactin, hPL, GH
Small peptides: GnRH, oxytocin

Question 2

hCG

• What is its the structure?
• Where is it secreted from?
• Where does it act?
• What are its 3 functions?
• Describe renal excretion and its clinical application
• How do levels change during pregnancy?

Answer 2

• glycoprotein - alpha and beta subunits
• secreted from syncytiotrophoblast
• acts of LH receptors
• functions: maintain CL, stimulate DHEA production in the foetal adrenals, in males, stimulates testosterone –> virilisation
• beta subunit renal excreted, pregnancy test
• levels double every 48hours in pregnancy

Question 3

Progesterone

• what is it secreted by?
• what are its functions?
• give a clinical application
• what are its effects on the endometrium?
• any other effects?

Answer 3

• secreted by CL initially, then placental secretion occurs between 6-8 weeks
• maintains the decidua, relaxes the myometrium
• progesterone essential to continuation of pregnancy, administration of progesterone inhibitor (Miferpristone) also resulted in pregnancy loss
• Endometrium - decidual transformation, immune modulation
• via progesterone receptor B, downregulates synthesis of contractile associated proteins such as fat junctions and oxytocin receptors. negatively regulates human placental lactogen

Question 4

Describe how progesterone is a substrate for sterioidgenesis?
What enzymes are lacking in the feotus and the placenta and what are the implications of this?

Answer 4

• Placenta lacks 17alphahydroxylase and so cannot convert progesterone to DHEA
• Foetal adrenal glands lacks 3BHSD and so cannot convert pregnenolone to progesterone.
• These modifications result in an alternative pathway for oestrogen synthesis.
• Alternative pathway: cholesterol converted to DHEA in foetal adrenal, DHEA converted to estriol in foetal liver, reenters maternal circulation

Question 5

List the 3 types of oestrogen

When does each predominate?

Answer 5

Oestrone = E1 --> predominates in menopause 
Oestradiol = E2 --> regulates menstruation 
Oestriol = E3 --> pregnancy specific (by-product of sterioidogenic pathway)

Question 6

What is the role of oestrogen following implantation?

Answer 6

• main source is the and the foetal liver
• oestradiol, E2 is the most patient
  Maternal effects:
• vascular changes
• increase is prothrombotic mechanisms –> increase protein C, decrease ATIII and Protein S
• increase contractile associated proteins (opposite of progesterone), gap junctions, oxytocin, breast development

Question 7

What is the role of placental growth hormone (PGH)?

Answer 7

• secretion starts from 15-20 weeks
• modifies receptors which transport glucose across eh foetal compartment
• non-pulsatile secretion, levels correlate with placental size
• stimulates maternal gluconeogenesis and lipolysis
• no functional GH receptor until near term

Question 8

What is another name for HPL
Where is it secretion from
What is its function

Answer 8

• also called human chorionic somatomammotropin
• secreted from syncytiotrophoblast
• functions as a metabolic screwdriver by chi foetus resets maternal CHO homeostasis
• short half life of 15 minutes

Question 9

What are the main effects of HPL?

Answer 9

• induces breast maturation
• increased IGF-1, insulin resistance increases, lipoylsus and gluconeogeneis increases
• -> increase glucose and ketones to foetus

Question 10

Overall what is the effect of HPL and PGH?

Answer 10

• increased maternal glucose for the foetus

Question 11

Is progesterone pro-contractile or pro-relaxant?

Is oestradiol pro-contractile or pro-relaxant?

Answer 11

progesterone = pro-relaxant 
oestradiol = pro-contractile

Question 12

How do estradiol and progesterone regulate partuition?

Answer 12

• progesterone suppreses myometrial contraciton, preventing birth
• does this by regulating oestrogen receptors

Question 13

What is meant by cervical effacement?

Answer 13

• thinning of the cervix
• collagen fibres reduce
• glycosaminoglycans increased
• MMPs increase

Question 14

Describe Friedman’s partogram

Answer 14

• analysis of 500 women during labour
• changes in cervical dilation from the latent to the active phases takes on a sigmoidal shop e
• multiparae attain active phase faster than nulliparas

Question 15

What are the features of the latest and active phases of labour?

Answer 15

• latent phase = cervial changes

- active phase = progressive cervical dilation

Question 16

What is the Ferguson reflex?

Answer 16

• neuroendocrine reflex
• spinal reflex where pressure of head on cervix induces oxytocin release
• stimulate sympathetic and parasympathetic nerve to dorsal column
• positive feedback

Question 17

Describe the oxytocin signalling pathway

Answer 17

• Ca2+ required for muscle contraction
• Ca2+ enters SM cells via voltage gated channels, binds to calmodulin –> SM contraction
• oxytocin binds to receptor, increases opening of these channels and induces Ca2+ release from endoplasmic reticulum

Question 18

What are the role of prostaglandins in parturition?

Answer 18

• synthesised in cell/organelle membranes
• half life of 3-10 mounts
• PGF2aloha and PGE2 are PROCONTRACTILE
• oestrogen destablises lysosomes to increase PLA2, progesterone stabilises lysosomes to decrease PLA2

Question 19

What is the foetal contribution to initiation of labour?

Answer 19

• Placental CRH (corticotrophinreleaing hormone) increases with increasing gestation
• DHEAS increases vie foetal adrenal gland
• conversion to oestradial occurs in the placenta
• some oestradiol metablised to DHEA-S in maternal liver
• mos has pro contractile myometrial effects

Question 20

Describe the role of oestrogen in breast feeding

Answer 20

• Increasing oestrogen during pregnancy causes hypertrophy and hyperplasia of breast tissue
• Also induces prolactin release directly and indirectly via suppressing dopamine
• explosion of placenta, oestrogen withdrawal –> letdown effect

Question 21

What are the advantages of breastfeeding for the baby?

Answer 21

• protects against infection, illness and allergy
• possible enhancement of devlepomemtn and intelligence
• long term health benefits (e.g. dental health, diabetes, cancer, autoimmune diseases)

Question 22

Whet are the advantages of breastfeeding for the mother?

Answer 22

• contraception
• reduce cancer risk e..g breast, ovarian, endometrial
• emotional health
• weight loss (500kCal/day)

Question 23

What are the key lactation and breastfeeding messages?

Answer 23

• PRL and HPL contribute to breast development
• PRL is responsible for milk production
  Sucking increases
• PRL release which maintains milk production
• oxytocin release which causes SM contraction and thus milk ejection