Endocrinology of pregnancy Flashcards
hCG
function + structure
- α & β subunits
- α subunit identical to LH, FSH and TSH
Function
- Acts on LH receptors on corpus luteum
- Maintains corpus luteum
- Stimulates DHEA production in fetal adrenal
In males – stimulates testosterone → masculinisation
When can hCG be dected and when does it stop
in early pregnancy doubles every 48 hrs
detected days 8-12 + stops around 12 weeks
- clinically used to measure if there’s problem
- if it doesn’t rise by 60% in 48 hours their can be problems
- progesterone may be given early pregnancy
What synthesises hCG
synctitrophoblast
What happens if you block hCG via antibodies
block pregnancy
how?
hormone keeps progesterone levels good, no progesterone no endometrium to implant into
Progestrone
function, where produced
Initially produced from corpus luteum
Produced from cholesterol by syncytiotrophoblast – the placenta takes over from corpus luteum ~6-8 weeks
Function
-maintains pregnancy
-affects myometrium: how -> decreses syntheise of contractile protiens, via progestrone b recpetor
-inhibits expression of oxytoxin receptors on myometrium during pregnancy
-Decidual transformation/maintenance (you know viilli, spiral arteries, Immune suppressive effect)
How can oestrogen be made
- cholesterol taken and converted in placenta to from pregnalalone to progesterone
- progesterone can be processed by fetal adrenal or liver, to make 17, OH then converted to DHEA
- DHEA can go back to the mother that is a conjugated sulfate
- so mum can take in DHEA, and convert it into oestrogen which makes de conjugated
What are the three oestrogens and their roles
- Oestrone, E1: Predominates after menopause
- Oestradiol, E2: Regulates menstruation
- Oestriol, E3: Pregnancy-specific
What happens to oestrogen during pregnancy
rises throughout pregnancy
Oestriol production predominates (oestriol»_space; oestrone & oestradiol)
Produced co-operatively by the placenta and fetus
What form is oestrogen in
- hormones bound to carrier proteins
- and are sulfated means they are inactive
- and then they are deconjugated in placenta
What is the role of oestrogen after implanation
**Vascular changes
**
- Vasodilation – increase uterine blood flow
- Increase in prothrombotic mechanisms
- Activated Protein C resistance increases
- Antithrombin III and Protein S decrease
- slight increase in risk of thrombosis in pregnancy
**Increase contractile-associated proteins
**– Gap junctions (e.g. Connexin 43), Oxytocin & its receptors, Myometrial glycogen stores, Breast development (for lactation)
**Metabolism
**
- reduces peripheral glucose uptake
- increases cholesterol & triglycerides – decreases HDL
Breast development
When does placental growth hormone (PGH) secretion start
Secretion starts from 15-20 weeks from syncytiotrophoblast & EVTs
What is PGH role
- Stimulates maternal gluconeogenesis & lipolysis
- aids nutrition across placenta
What do PGH levels correlate with
Non pulsatile
So Levels correlate with placental size
- big fetus big placneta
- levels correlate with placenta size
What hormones are related to human placental lactogen
GH & PRL
Where is human placental lactogen produced and what is its function
-Produced by the syncytiotrophoblast
Stimulates gluconeogenis and lipolysis
What happens to HPL levels
Rises as hCG falls
What is the role of HPL
-Development of acinar cells in mammary glands
- ready for milk production
- Aids fetal nutrition
Suppresses action of insulin in mother – “acts as metabolic screwdriver”
- increases blood glucose levels – more available to the fetus
- glucose goes across on a gradient
- hormone allows gradient to be maintained
- stops peripheral uptake of glucose
- which can lead to insulin sensitivity
- mobilises maternal FAs to meet fetal demand
Increases risk of GD
Large amounts in maternal blood – little reaches fetus
- IGF -1 produced by the liver which leads to insulin resistance and break down of fats
- so you get an increase of glucose to the fetus, and steroids synthesis happens on placenta
What is the structure of relaxin and where is it produced
Structure
Peptide hormone ~6 kDa related to insulin
Proudced by
produced by corpus luteum
-can be made during menustration
What is the function of relaxin
Function
- Increases cardiac output and arterial compliance
- Increases renal blood flow
- Relaxes pelvic ligaments and is believed to soften pubicsymphysis, also promotes cervical ripening
What happens to relaxin levels
Levels rise in 1st trimester – peaks at ~14 weeks and again at delivery
What is the role of prolactin
- important for milk production
- stimulated by growth hormone
where is prolactin made
synthesised by lactotrophs in anterior pituitary gland
what happens to prolactin levels during pregnancy
rises linearly through pregnancy
How do you keep prolactin levels up
breastfeeding needed to maintain levels
What stimulates prolactin release
oestrogen
What are the stages of delievry
- Contractions begin, dilation & shortening/effacement of cervix
- Full dilation of cervix – delivery of baby
- Delivery of placenta
What mediates parturition
- Increase in oestrogen compared to progesterone which must be suppressed
- release prostaglandins (PGF2α, PGE2)
- important in contraction and modifying the cervix
- Oxytocin
- drives contraction
What happens to oxytocin receptors in pregnancy
- increase towards the end
- oxytocin promotes spontaneous depolarisation of myometrium muscle
- secreted by posterior pituitary and decidual tissue
What is CRH a precursor for
ACTH
when do we release CRH
when we are stressed
What is the function of CRH
- Stimulates corticosteroid production from adrenals
- CRH & CRH receptor in the placenta/decidua increase at term – CRH binding protein decreases.
Glucocorticoids/cortisol levels increase
- fpr lung maturation – synthesis of surfactants
- promote oestrogen & prostaglandin production
How does the fetus contribute to labour
- Placental CRH increases during gestation
- causes DHEAS increases via fetal adrenal gland
- this is Converted to oestradiol in the placenta → this has procontactile myometrial effects
What is the role of prostoglandins
cervical ripening
- stimulation of the cervix due to the production of prostaglandins
- sex can also stimulate prostaglandins
- any irritation of cervical tissue will release prostaglandins
What happens to cervical remodelling
-loosening of collagen fib res
-cervix moves posterior and gets thinner and smoother
-increased glycosaminoglycans e.g hyaluron
-increased matrix metalloproteinase production e.g collagenase
-increased inflammatory cells and cytokines
Oxytocin
where is it made, function,
- Nonapeptide produced by neurohypophysis
- released by the posterior pituitary
-promotes love and stuff
-stimulates post birth contractions so uterus goes to right place - Oestrogens main stimulators of oxytocin synthesis
- Lowers the excitation threshold of the myometrial muscle cell at which spiking occurs
- allows for contraction
- Released in response to tactile stimulation of the uterine cervix
- Operates through a neuroendocrine pathway – Ferguson Reflex
Describe the neuroendocrine reflex
1.Intramyometrial PGF2 increases uterine contractions + cervical distension
2.this is sensed by neurones
3.causes release of oxytocin
4.oxytocin promotes further uterine contractions and release of prostoglandins
Describe anatomy of breast
- 15-20 lobes of glandular tissue interspaced with fibrous/adipose tissue
- Lobes – lobules of alveoli, blood vessels & lactiferous ducts
- Alveoli – epithelial “Acinar” cells – synthesise milk
- myoepithelial cells – contract to move milk to lactiferous ducts for ejection
What is the difference in lactiforius ducts at birth and puberty
- At birth – mostly lactiferous ducts, few alveoli
- Puberty – oestrogen stimulates lactiferous ducts sprout and branch, alveoli start to develop, deposition of fat & connective tissue
What hormones are involved in breastfeeding
Oestrogen – increases size & number of ducts in the breast
-also causes PRL secretion -which suppresses dopamine
Progesterone – increases the number of alveolar cells - but inhibits lactogenic effects of prolactin
hPL – stimulates the development of acinar glands
Prolactin – levels increase with gestation & promote milk production
oxytocin: promotes let down or milk ejection reflex
In summary what does prolactin and oxytocin do in breastfeeding
-prolactin causes milk production
-prolcatin maintains milk production
-oxytocin release causes smooth milk contaction -> ejection of milk
Quick pathway of lactation
sucking (stimulas)
goes to hypothalamus
hypothalamus causes release of prolactin and oxytocin from pituritaty
oxytocin-> milk release
prolactin -> milk production
How to maintain milk production
what can inhibit production, increase etc
-prolactin release is positive feedback
-Tuberoinfundibulardopamine (TIDA) is a neurone -> its actovity id modulated by reducing dophamine secretition
-dophamine agonists (e.g bromocriptine) inhibit prolactin
-vasointestinal peptide (VIP) + the release causes prolactin secretion
Describe the milk ejection reflex
1.Nipple stimulated by suckling
2.causes release oxytoxin
3.oxytocin stimulates breast myoepithelial cell contraction
4.causes milk release from alveoli + increase ductal flow of milk to nipples
5.can promote uterine contraction
What are the advantages of breast-feeding for the baby
- Enhances development and intelligence
- Protects against infection, illnesses and allergies
- Has long term health benefits
What are the advantages of breast feeding for the mother
- Can delay fertility
- reduce risk of gynacological cancer
- improve emotional health
- cause weight loss
- protec against oestoprorosis
Latent v active phase of labour
Latent
-contractions
-last for about a few weeks
Relaxin acts on pubic symphysis
Active
Short regular contractions
What is the role of progesterone 3 and 4
Prog3trone 3; contraction
Progesterone 4: relaxation produced after labour
