it 7 - obstetri fisiologi (hormon plasenta) - izq
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The Placental Hormones
OLEH:Dr. H. Iskandar Zulqarnain, SpO !"#
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INDEX
HUMAN CHORIONIC GONADOTROPIN (hCG)1
HUMAN PLACENTAL LACTOGEN (hPL)2
HYPOTHALAMIC-LIKE RELEASING HORMONES4
ESTROGENS6
OTHER PLACENTAL PEPTIDE HORMONES5
OTHER PLACENTAL PROTEIN HORMONES3
FETAL ADRENAL GLANDS7
MATERNAL CONDITIONS THAT AFFECT PLACENTAL ESTROGEN FORMATION
8
PROGESTERONE9
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The human placenta synthesize an enormous amount of hormones
: hPL, hCG, ACTH, PTH-rP, GH variant, calcitonin, relaxin
hypothalamic-like releasing and inhibiting hormones T!H, Gn!H, C!H, somatostatin, GH!H"
inhibins, activins, A#P
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HUMAN CHORIONIC GONADOTROPIN
hCG
$$ pregnancy hormones%
$ prod&ced almost excl&sively in the placenta
$ detection o' hCG in blood or &rine
- indication o' pregnancy
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$ glycoprotein H - hCG, ()H, LH, T)H
$ t*o s&b&nits - + s&b&nits identical - s&b&nits distinctly di''erent
1. Chemical Characteristics
2. Biosynthesis $ single gene chromosome . at /01-/10"
- codes 'or +-s&b&nit $ eight separate gene chromosome 02"
- Codes 'or -hCG3 -LH 'amily
HUMAN CHORIONIC GONADOTROPIN
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- complete hCG molec&le is synthesi4ed primarily in the syncytiotrophoblast
3. Cellular Sites of Origin
4. egulation of hCG Su!unit Biosynthesis- The amo&nt o' m!#A 'or hCG in syncytiotrophoblast 'rom the 'irst trimester are greater than at term
5 the meas&rement o' hCG in plasma as a screening proced&re to identi'y abnormal 'et&ses
HUMAN CHORIONIC GONADOTROPIN
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$ 0st detection : 6 031 to 2 031 days a'ter the LH s&rge
$ maximal levels : abo&t 7 to 08 *eeks $ begin to decline : abo&t 08 to 01 *eeks $ nadir : abo&t 18 *eeks $ maintained at this lo*er level
'or remainder o' pregnancy
". Concentrations of hCG in Serum # $rine
HUMAN CHORIONIC GONADOTROPIN
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$ elevated : m<iple 'et&ses, erythroblstotic 'et&ses,
hydatidi'orm mole, choriocarcinoma9
o*n syndrome
$ depressed : ectopic pregnancy impending
spontaneo&s abortion
%. &le'ate( or )epresse( hCG *e'els
HUMAN CHORIONIC GONADOTROPIN
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- resc&e and maintenance o' '&nction o' corp&s l&te&m- stim&late o' 'etal testis : to promote male sex&al di''erentiation- stim&late o' maternal thyroid : increases thyroid activity,
stim&late iodine &ptake- other : promote relaxin secretion
+. Biological ,unction
HUMAN CHORIONIC GONADOTROPIN
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- single non-glycosylated polypeptide chain
- similar to hP!L prolactin"
1. Chemical Characteristics
h-* - potent lactogenic and GH-like bioactivity
HUMAN PLACENTAL LACTOGEN
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- hPL on chromosome 06- hP!L on chromosome .
2. Gene Structure
3. Serum Concentration
$ demonstrable in placenta *ithin ; to 08 days a'ter conception
$ detected as early as < *eeks a'ter 'ertili4ation $ rises &ntil abo&t
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- stim&lated : ins&lin, cA>P
- inhibited : PG? 1, PG( 1+
4. egulation of h-* Biosynthesis
". eta!olic /ctions
@ lipolysis and increase ((A
anti-ins&lin action
HUMAN PLACENTAL LACTOGEN
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1. Chorionic /(renocorticotropin - ACTH, lipotropin, -endorphin
2. Chorionic Thyrotropon
3. ela0in - acts on myometrial smooth m&scle to promote &terine relaxation
4. -T r-". hG 'ariant
OTHER PLACENTAL PROTEIN HORMONES
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1. Gn
HYPOTHALAMIC-LIKE RELEASING HORMONES
$ imm&noreactive Gn!H *as present in cytotrophoblast
2. C !iological function
- 'etal adrenal steroidogenesis
- smooth m&scle relaxation - imm&nos&ppression
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HYPOTHALAMIC-LIKE RELEASING HORMONES
le'el - nonpregnant 0; pg3mL - early third trimester 1;8 pg3mL - last ; to . *eeks 0888 to 1888 pg3mL
cushing syn(rome that (e'elope( (uring pregnancy ith spontaneous resolution after (eli'ery
5 placental C!H stim&lated pit&itary ACTH 'ormation
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HYPOTHALAMIC-LIKE RELEASING HORMONES
positi'e fee(!ac
: placental C!HB 5 placental ACTHB
5 gl&cocorticosteroid 'ormationB 5 placental C!H expressionB
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1. 5europepti(e 6
2. 7nhi!in an( /cti'in
3. /trial 5atriuretic -epti(e 8/5-9
OTHER PLACENTAL PEPTIDE HORMONES
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ESTROGENS
$ placenta prod&ce h&ge amo&nts o'
estrogen, progesterone
$ near tern : hyperestrogenic state
$ prod&ced by syncytiotrophoblast
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ESTROGENS
1. Biosynthesis19 nonpregnant : pro(uce( in the o'arian follicle
in theca cell"acetatecholesterol
androstenedione
taken &p gran&losa cell"estradiol 06 synthesis
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ESTROGENS
29 pregnant - neither acetate nor cholesterol, nor even progesterone can serve as prec&rsor - C02 -steroids convert to estrone and estradiol-06 - C02 -steroids : dehydroepiandrosterone, androstenedione, and testosterone - plasma C 02 -steroids are estrogen prec&rsors
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ESTROGENS
2. -lacental /romatase &nzyme $ en4yme complex that cataly4e estrogen 'ormation
'rom androstenedione
$ - Cyt P-=;8 monooxygenase - aromatase cytochrome P-=;8 - 'lavoprotein
- #A PH-cytochrome P-=;8 red&ctase
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ESTROGENS
3. Secrete( &strogens o'ary
: androstenedione 5 estrone 5 estradiol-06 a(ipose tissue
: androstenedione 5 estrone human placenta
@ estradiol-06
0.+-hydroxyandrostenedione 5 0.+-hydroxyesterone 5 estriol
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FETAL ADRENAL GLANDS
,etal /(renal Glan(s- compared *ith ad< organs, the adrenal cortex is the largest organ o' the 'et&s- more than 7; o' 'etal gland is normally composed o' a pec&liar 'etal 4one not in ad<s"
1. Contri!ution to -lacental &strogen ,ormation $ near term, estradiol-06 prod&ced in placenta
- hal' 'rom maternal - hal' 'rom 'etal plasma
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FETAL ADRENAL GLANDS
2. -lacental &striol Synthesis $ nonpregnant
&rine estriol : estrone D estriol-06 E 0 : 0
$ near term, this ratio increases to 08 or more$ 0.+-hydroxylated C02-steroids - converted to estriol by placental tiss&e - is synthesi4ed by the 'etal adrenal and liver
$ near term, 'etal so&rce 28F" maternal so&rce 08 "
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FETAL ADRENAL GLANDS
&2
&3
/(renal)S
*i'er
1%; O )S
&2-lacenta
&3
&2/(renal )S1%; O )S
*i'er 1%; O )S
&3
aternalCompartment ,etus
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FETAL ADRENAL GLANDS
3. ,etal /(renal )e'elopment $ in early embryo, adrenal cortex is composed o' cells
- proli'erate rapidly prior to vasc&lari4ation
o' pit&itary gland5 comprise 'etal 4one
$ ACTH is secreted by - 'etal pit&itary gland - chorionic ACTH syncytiotrophoblast
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FETAL ADRENAL GLANDS
4. &nzymatic Consi(erations $ de'iciency o' < -hydroxysteroid dehydrogenase
5 limit the conversion o'
- pregnenolone 5 progesterone - 06+-hydroxypregnenolone 5 06+-hydroxyprogesterone
$ very active steroid s&l'otrans'erase
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FETAL ADRENAL GLANDS
". ,etal /(renal Steroi( -recursor
- L L cholesterol
- is synthesi4ed 'etal adrenal 5 convert to 0.+- H C 02 steroid in 'etal liver
5 placenta
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FETAL ADRENAL GLANDS
%. ,etal Con(itions that /ffect &strogen -ro(uction
@ 'etal death - striking red&ction in the levels o' &rinary estrogens 'etal anencephaly n the absence o' the 'etal 4one" - limited availability o' C 02 -steroid prec&rsors
5 rate o' 'ormation o' placental estrogens is severely limited
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FETAL ADRENAL GLANDS
I 'etal adrenal hypoplasia - estrogen 'ormation is very limitedJ placental s&l'atase de'iciency - precl&des the hydrolysis o' C 02 -steroid s&l'ates
K-linked disorder" placental aromatase de'iciency - androstenedione co&ld not converted to estradiol-06
M do*n syndrome - ser&m &nconN&gated estriol levels *ere lo* - screening o' 1nd trimester
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FETAL ADRENAL GLANDS
O de'iciency in 'etal L L biosynthesis - lead to no progesterone 'ormation - estriol levels *ere also lo*er than normal
'etal erythroblastosis - estrogen levels in maternal plasma are elevatedQ decreased 'etal adrenal &se o' L L - most common ca&se o' decreased placental estrogen 'ormation
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@ gl&cocorticosteroid treatment - inhibit ACTH secretion 5 maternal F 'etal adrenal secretion is decreased
5 ca&ses striking red&ctionin placental estrogen maternal adrenal dys'&nction - estrone and estradiol-06 is decreased
I maternal ovarian androgen-prod&cing t&mors - precl&ding transplacental passage
MATERNAL CONDITIONS THAT AFFECT PLACENTAL ESTROGEN FORMATION
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J maternal renal disease - lo*er level o' estriol in &rine maybe observed maternal HT# and > - decreased &teroplacental 'lo* 5 'etal 'ormation o' dehydroepiandrosterone is impairedM gestational trophoblastic disease - in H-mole or choriocarcinoma, there is no 'etal adrenal so&rce o' C 02 -steroid prec&rsor, estrogen 'ormation is limited
MATERNAL CONDITIONS THAT AFFECT PLACENTAL ESTROGEN FORMATION
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PROGESTERONE
1. Source of Cholesterol for -lacental-rogesterone Biosyntheis
$ cholesterol in mitochondria" cytochrome P=;8 5 pregnenolone 5 progesterone < -hydroxysteroid dehydrogenase
% to + ee s of gestation < pro(uce( in the o'ary
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PROGESTERONE
2. -rogesterone Synthesis an( ,etal =ell Being
$ relationship bet*een 'etal *ell-being and placental
estrogen cannot be demonstrated in the case o'
progesterone
$ th&s, progesterone biosynthesis may persist
'or long periods a'ter 'etal death
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PROGESTERONE
3. -rogesterone eta!olism )uring -regnancy
@ ;+-dihydroprogesteroneB
progesterone is converted to the potent mineralocorticosteroid deoxycorticosterone
in pregnant *omen and in the 'et&s
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