Zusammenfassung
Unser Wissen über die biochemischen und physiologischen Prozesse, die die Geburt beim
Menschen steuern, hat im letzten Jahrzehnt stark zugenommen. Zahlreiche neue Befunde
geben Aufschluss über spezifische Funktionen der beteiligten Signalstoffe bei der
Zervixreifung, der Aktivierung des Uterus und der Stimulation des Myometriums. In
diesem Zusammenhang wurden Sexualsteroide, Oxytocin, Prostaglandine, Corticotropin-Releasing
Hormon (CRH) und Zytokine am intensivsten erforscht. Dabei wurden positive Regelkreise
in der fetoplazentaren Einheit entdeckt, die den Geburtsprozess in irreversibler und
eskalierender Weise vorantreiben. Weiterhin wurde erkannt, dass sich der Organismus
bei der Wehentätigkeit in selektiver und kontrollierter Weise entzündungsähnlicher
Reaktionen bedient. Zur Erklärung des Geburtszeitpunktes beim Menschen wurden neue
Modelle formuliert. So diente der Befund, dass die maternalen Serumspiegel von bioverfügbarem
CRH beim Menschen vor der Geburt stark ansteigen, als Basis für die Hypothese, dass
CRH wichtiger Indikator einer plazentaren Uhr ist, die die Dauer der Schwangerschaft
bestimmt. Nach einer anderen Hypothese wird die Reifung der fetalen Hypothalamus-Hypophysen-Nebennierenrinden-Achse
durch eine plazentare Inaktivierung von mütterlichem Cortisol induziert. Offene Fragen
bestehen nach wie vor bezüglich der Bedeutung weiterer Signalstoffe und des Verständnisses
der zeitlichen und räumlichen Koordination der beteiligten physiologischen Prozesse.
Summary
The biochemical and physiologic processes controlling labor in the human have become
much clearer in the past decade. Research has shed light on signal mediators governing
ripening of the cervix, activation of the uterus, and stimulation of the myometrium.
Sex steroids, oxytocin, prostaglandins, corticotropin-releasing hormone (CRH) and
cytokines have been studied intensively. The fetoplacental unit contains positive
feed-back loops triggering the birth process in an escalating and irreversible manner.
Inflammatory-like reactions occur in a controlled and selective manner during parturition.
New models have been developed to explain the timing of birth. Bioavailable maternal
CRH levels increase strongly near term, suggesting that CRH is an indicator of a placental
clock determining the duration of pregnancy. In another model, the birth process is
initiated by placental inactivation of maternal cortisol, thus inducing maturation
of the fetal hypothalamic-pituitary-adrenocortical axis. How other signal mediators
are integrated and how the various processes are coordinated remains unclear.
Literatur
- 1
Brodt-Eppley J, Myatt L.
Prostaglandin receptors in lower segment myometrium during gestation and labor.
Obstet Gynecol.
1999;
93
89-93
- 2
Bryant-Greenwood G D, Schwabe C.
Human relaxins: chemistry and biology.
Endocrine Rev.
1994;
15
5-26
- 3
Challis J R, Matthews S G, Gibb W, Lye S I.
Endocrine and paracrine regulation of birth at term and preterm.
Endocrine Rev.
2000;
21
514-550
- 4 Challis J RG, Lye S J.
Parturition. Knobil E, Neill JD The physiology of reproduction. 2. Aufl. New York; Raven Press
1994: 985-1031
- 5
Chwalisz K, Garfield R E.
Regulation of the uterus and cervix during pregnancy and labor. Role of progesterone
and nitric oxide.
Ann NY Acad Sci.
1997;
828
238-253
- 6
Clifton V L, Read M A, Leitch I M, Boura A LA, Robinson P J, Smith R.
Corticotropin-releasing hormone-induced vasodilation in the human fetal placental
circulation.
J Clin Endocrinol Metab.
1994;
79
666-669
- 7
Denison F C, Kelly R W, Calder A A, Riley S C.
Cytokine secretion by human fetal membranes, decidua and placenta at term.
Hum Reprod.
1998;
13
3560-3565
- 8
Dudley D J.
Pre-term labor: An intra-uterine inflammatory response syndrome?.
J Reprod Immunol.
1997;
36
93-109
- 9 Egarter C, Husslein P. Geburtsregulation und Wehensteuerung. Stuttgart; Wissenschaftliche
Verlagsgesellschaft 1998
- 10 Garfield R E, Buhimschi I A, Buhimschi C, Ali M, Saade G, Shi L, Chwalisz K.
Regulation of uterine and cervical function by nitric oxide. Lancaster JR, Parkinson JF Nitric oxide cytochromes P420, and sexual steroid hormones. Berlin;
Springer 1997: 141-180
- 11
Germain A, Smith J, Casey M L, MacDonald P C.
Human fetal membrane contribution to the prevention of parturition: Uterotonin degradation.
J Clin Endocrinol Metab.
1994;
78
463-470
- 12
Gibb W.
The role of prostaglandins in human parturition.
Ann Med.
1998;
30
235-241
- 13
Karalis K, Goodwin G, Majzoub J A.
Cortisol blockade of progesterone: A possible molecular mechanism involved in the
initiation of human labor.
Nat Med.
1996;
2
556-560
- 14
Kelly R W.
Pregnancy maintenance and parturition: The role of prostaglandin in manipulating the
immune and inflammatory response.
Endocrine Rev.
1994;
15
684-706
- 15
Kelly R W.
Inflammatory mediators and parturition.
Rev Reprod.
1996;
1
89-96
- 16 Liggins G C.
Cervical ripening is an inflammatory reaction. Ellwood DA, Anderson ABM The cervix in pregnancy and labour. Edinburgh; Churchill
Livingston 1981: 1-9
- 17
Majzoub J A, McGregor J A, Lockwood C J, Smith R, Snyder Taggart M, Schulkin J.
A central theory of preterm and term labor: Putative role for corticotropin-releasing
hormone.
Am J Obstet Gynecol.
1999;
180
S232-S241
- 18 Marks F, Fürstenberger (Eds) G. Prostaglandins, leukotrienes and other eicosanoids.
From biogenesis to clinical application. Weinheim; Wiley-VCH 1999
- 19
Mc Lean M, Bisits A, Davies J, Woods R, Lowry P, Smith R.
A placental clock controlling the length of pregnancy.
Nat Med.
1995;
1
460-463
- 20
Narahara H.
Role of PAF in parturition.
Adv Exp Med Biol.
1996;
416
269-275
- 21
Norwitz E R, Robinson J S, Challis J RG.
The control of labor.
N Engl J Med.
1999;
341
660-666
- 22
Olson D M, Mijovic J E, Sadowsky D W.
Control of human parturition.
Sem Perinatol.
1995;
19
52-63
- 23
Patel F A, Clifton V, Chwalisz K, Challis J.
Steroid regulation of prostaglandin dehydrogenase activity and expression in human
term placenta and chorio-decidua in relation to labor.
J Clin Endocrinol Metab.
1999;
84
291-299
- 24
Pepe G J, Albrecht E D.
Action of placental and fetal adrenal steroid hormones in primate pregnancy.
Endocrine Rev.
1995;
16
608-648
- 25
Perrin M H, Vale W W.
Corticotropin releasing factor receptors and their ligand family.
Ann NY Acad Sci.
1999;
885
312-328
- 26
Rath W, Kemp B, Heyl W.
Prostaglandin-E2-Vaginalgel versus Intrazervikalgel und Vaginaltablette in Abhängigkeit
vom Zervixstatus - Ergebnisse einer prospektiven randomisierten Multizenterstudie
zur Geburtseinleitung.
Geburtsh Frauenheilk.
1999;
59
323-329
- 27
Robinson B G, Emanuel R L, Frim D M, Majzoub J A.
Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human
placenta.
Proc Natl Acad Sci USA.
1988;
85
5244-5248
- 28
Roeb E, Rose-John S.
Zytokine: Biologie und therapeutische Relevanz.
Dtsch Med Wschr.
1996;
121
803-809
- 29
Schäfer W R, Zahradnik H P, Arbogast E, Wetzka B, Werner K, Breckwoldt M.
Arachidonate metabolism in human placenta, fetal membranes, decidua, and myometrium:
Lipoxygenase and cytochrome P450 metabolites as main products in HPLC profiles.
Placenta.
1996;
17
231-238
- 30
Sehringer B, Schäfer W R, Wetzka B, Deppert W R, Brunner-Spahr R, Benedek E, Zahradnik H P.
Formation of inflammatory cytokines in human term myometrium is stimulated by lipopolysaccharide
but not by corticotropin releasing hormone.
J Clin Endocrinol Metab.
2000;
85
4859-4865
- 31
Smith R.
The Timing of Birth.
Scientific American.
1999;
280
50-57
- 32
Smith R, Mesiano S, Chan E C, Brown S, Jaffe R B.
Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone
sulfate secretion by human fetal adrenal cortical cells.
J Clin Endocrinol Metab.
1998;
83
2916-2920
- 33
Steinborn A, Gall C, Hildenbrand R, Stutte H J, Kaufmann M.
Identification of placental cytokine-producing cells in term and preterm labor.
Obstet Gynecol.
1998;
91
329-335
- 34
Stevens M Y, Challis J RG, Lye S J.
Corticotrophin-releasing hormone receptor subtype 1 is significantly up-regulated
at the time of labor in the human myometrium.
J Clin Endocrinol Metab.
1998;
83
4107-4115
- 35
Thomson A J, Telfer J F, Young A, Campbell S, Stewart C JR, Cameron I T, Greer I A,
Norman J E.
Leukocytes infiltrate the myometrium during human parturition: further evidence that
labour is an inflammatory process.
Hum Reprod.
1999;
14
229-236
- 36
Vince G, Shorter S, Starkey P, Humphreys J, Clover L, Wilkins T, Sargent I, Redman C.
Localization of tumor necrosis factor production in cells at the materno/fetal interface
in human pregnancy.
Clin Exp Immunol.
1992;
88
174-180
- 37
Weber-Fehr B, Winkler M, Fischer D C, Ruck P, Kemp B, Rath W.
Zytokine, endotheliale Adhäsionsmoleküle und neutrophile Granulozyten im unteren Uterinsegment
bei Frühgeburt.
Geburtsh Frauenheilk.
1999;
59
103-106
- 38
Winkler M, Fischer D C, Hlubek M, van der Leur E, Haubeck H D, Rath W.
Interleukin-1 beta and interleukin-8 concentrations in the lower uterine segment during
parturition at term.
Obstet Gynecol.
1998;
91
945-949
- 39
Winkler M, Rath W.
Changes in the cervical extracellular matrix during pregnancy and parturition.
J Perinat Med.
1999;
27
45-60
PD Dr. rer. nat. W. R. Schäfer
Universitäts-Frauenklinik
Klinisch-Chemisches Labor
Hugstetter Straße 55
79106 Freiburg
eMail: WSCHAEF@frk.ukl.uni-freiburg.de
