IT 7 - Obstetri Fisiologi (Hormon Plasenta) - IZQ

8/9/2019 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



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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



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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



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$ elevated : m&ltiple '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



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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



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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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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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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&lt 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&lts"

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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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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&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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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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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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". ,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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%. ,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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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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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



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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



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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

IT 7 - Obstetri Fisiologi (Hormon Plasenta) - IZQ

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Transcript of IT 7 - Obstetri Fisiologi (Hormon Plasenta) - IZQ