Hormonesofpregnancy

BuckHales
dhales@siumed.edu

Fromfertilizationtoimplantation

SubstancesSecretedbytheBlastocyst
Immunoregulatory Agents (prevent allograft rejection)
Platelet-activating factor (PAF)
Early pregnancy factor
Immunosuppressive factor
PGE2
Interleukins 1, 6, and 8
Interferon
Leukemia inhibitory factor
Colony-stimulating factor
Human leukocyte antigen 6
Fas ligand
Metalloproteases (facilitate invasion of trophoblast into the endometrium)
Collagenases: digest collagen types I, II, III, VII, and X
Gelatinases: two forms, digest collagen type IV and gelatin
Stromelysins: digest fibronectin, laminin, and collagen types IV, V, and VII
Serine Proteases (facilitate invasion of trophoblast into the endometrium)
Other Factors or Actions

hCG: autocrine growth factor

Ovum factor
Early pregnancy factor
Embryo-derived histamine-releasing factor
Plasminogen activator and its inhibitors
Insulin-like growth factor 2 (IGF-2): promotes trophoblast invasiveness
Estradiol
1 Integrin
Fibroblast growth factor (FGF)
Transforming growth factor (TGF-)
Inhibins

Uterine Secretions Nourish the Preimplantation Embryo,

Promote Growth, and Prepare It for Implantation
Mucins
Prolactin
Insulinlikegrowthfactorbindingprotein1(IGFBP1)
Placentalprotein14(PP14)orglycodelin
Pregnancyassociatedendometrial2globulin(2PEG)
Endometrialprotein15
Fibronectin
Laminin
Entactin
CollagentypeIV
Heparan sulfate
Proteoglycan
Integrins
Albumin
Lipoprotein
Relaxin
Acidicfibroblastgrowthfactor
Basicfibroblastgrowthfactor
PregnancyassociatedplasmaproteinA(PAPPA)
Stressresponseprotein27(SRP27)
CA125
Endorphin
Leuenkephalin
Diamine oxidase
Plasminogen activator(PA)
Plasminogen activatorinhibitor
Renin
Progesteronedependentcarbonicanhydrase
Lactoferrin
Table561.EndometrialProteins,Glycoproteins,andPeptidesSecretedbytheEndometrialGlandsDuringPregnancy

Hormonal
profileof
pregnancy

Figure567Maternallevelsofprogesteroneandtheestrogensjustbeforeandduringpregnancy.Theyaxisscaleislogarithmic. Thezeropointonthexaxisisthetimeoffertilization.
Theprogesteronespikesnear8and4weeksrefertothetwomenstrualcyclesbeforetheonethatresultedinthepregnancy.(DatafromWilsonJD,FosterDW,Kronenberg HM,Larsen
PR[eds]:WilliamsTextbookofEndocrinology,9thed.Philadelphia:WBSaunders,1998.)
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HormonesMadebythePlacenta
Peptide Hormones and Neuropeptides

hCG
Thyrotropin (thyroid-stimulating hormone [TSH])
Placental-variant growth hormone
hCS1 and hCS2, also known as hPL (hPL1 and hPL2)
Placental proteins PP12 and PP14
TRH
Corticotropin-releasing hormone (CRH)
Growth hormone-releasing hormone (GHRH)
GnRH
Substance P
Neurotensin
Somatostatin
Neuropeptide Y
ACTH-related peptide
The inhibins

Steroid Hormones

Progesterone
Estrone
Estradiol
Estriol

PlacentalHormones

MaternalFetoplacental Unit:steroidhormonesynthesis

RolesoftheMother,Placenta,andFetusinSteroidBiosynthesis
Mother

Needs

Contributes

Lacks

Progesterone

LDL cholesterol

Adequate synthetic capacity for

progesterone and estrogens

3-Hydroxysteroid dehydrogenase
aromatase (P-450arom)

Adequate cholesterol synthesizing capacity

Estrone
Estradiol
Estriol

Placenta

17-Hydroxylase (P-450c17; needed to

synthesize estrone and estradiol)
17,20-Desmolase (P-450c17; needed to
synthesize estrone and estradiol)
16-Hydroxylase (needed to synthesize
estriol)

Fetus

17-Hydroxylase (P450c17; needed to

synthesize estrone and estradiol)
17,20-Desmolase (P450c17; needed to
synthesize estrone and estradiol)
16-Hydroxylase (needed to synthesize
estriol)

3-Hydroxysteroid dehydrogenase
aromatase (P450arom)

Figure568Synthesisofprogesteroneandtheestrogensbythematernalplacentalfetalunit.Individualenzymesareshowninthehorizontalandverticalboxes.SeeFigures502,545,and559forcellular
localizationsofenzymes.Chemicalgroupsmodifiedbyeachenzymearehighlightedinthereactionproducts.Thefetuslacks3βhydroxysteroid dehydrogenase (3βHSD)andaromatase (P
450arom),shownonthebluebackground.Placentalacks17αhydroxylase and17,20desmolaseactivity(contributedbythesameprotein,P450c17)and16αhydroxylase,shownonthebrown
background.Theblueandbrowncolorcodingofenzymesdistinguishesfetusfromplacenta,whereascolorcodinginprevioussteroidogenesis figuresindicatessubcellular localization.
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Figure5511Twocell,twogonadotropinmodel.Duringthefollicularphase,themajorproductofthefollicleisestradiol,whereasduringtheluteal phase,themajorproductsofthecorpus
luteumaretheprogestins,althoughestradiolsynthesisisstillsubstantial.Inthefollicularphase,LHprimesthethecacelltoconvertcholesterol to androstenedione.Becausethethecacell
lacksaromatase,itcannotgenerateestradiolfromthisandrostenedione.Instead,theandrostenedione diffusestothegranulosa cell,whosearomatase activityhasbeenstimulatedbyFSH.
Thearomatase convertstheandrostenedione toestradiol.Intheluteal phase,thevascularization ofthecorpusluteummakeslowLDLavailabletothegranulosalutein cells.Thus,boththe
thecalutein andthegranulosalutein cellscanproduceprogesterone,themajorproductofthecorpusluteum.Forproductionof17αhydroxyprogesterone (17αOH
progesterone),someoftheprogesteronediffusesintothethecalutein cell,whichhasthe17αhydroxylase activityneededforconvertingtheprogesteroneto17α
hydroxyprogesterone.Thethecalutein cellcanalsogeneratetheandrostenedione,whichdiffusesintothegranulosalutein cellforestradiolsynthesis.AC,adenylyl cyclase.
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2005Elsevier

Figure569Theinteractionsofthematernalplacentalfetalunit.ThedetailsoftheenzymaticreactionsareprovidedinFigure 568.SCCEisthesidechaincleavageenzyme;theSin
DHEASand16αOHDHEASrepresentssulfate.17βHSD,17βhydroxysteroiddehydrogenase.

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Parturition
Oxytocin
stimulates
smooth muscle
contractions

Fetal
cortisol

Oxytocin
secretion
from
posterior
pituitary

Cortisol inhibits
progesterone
which promotes
contractions
Mechano
receptors
signal to
brain
Fetal CRH/
ACTH
Pressure
against
cervix

Parturition

Uterinewallcontractions