Cervical ripening in humans: potential roles of estrogen, progesterone, and insulin-like growth factor-I.
OBJECTIVE
During pregnancy in humans a gradual connective tissue remodeling takes place in the cervix. The aim of this study was to examine a possible relationship between the action of gonadal steroids and growth factors and the biochemically identifiable changes in connective tissues during cervical ripening.


METHODS
Cervical biopsy specimens and serum samples were taken from 20 term pregnant and 20 nonpregnant menstruating women. Estrogen receptors and progesterone receptors were measured with enzyme immunoassays. The messenger ribonucleic acid levels for estrogen receptors, progesterone receptors, and insulin-like growth factor-I were determined by solution hybridization with human complementary deoxyribonucleic acid probes. The concentration of collagen and its solubility by pepsin digestion were measured. Statistical evaluations were done with the Student t test.


RESULTS
In term pregnancy the estrogen receptor level decreased to 14% and the progesterone receptor level to 24% of nonpregnant levels (p <0.001 and p <0.01). The insulin-like growth factor-I messenger ribonucleic acid level increased 400% (p <0.01), whereas the messenger ribonucleic acid levels for estrogen receptors and progesterone receptors were unchanged. The changes coincided with a twofold decrease in collagen concentration (hydroxyproline) and a twofold increase in collagen solubility.


CONCLUSIONS
Estrogen receptors and progesterone receptors are present in human cervix. A significant down-regulation of estrogen receptors and progesterone receptors and a fourfold increase in the insulin-like growth factor-I messenger ribonucleic acid level were registered in term pregnant cervix. These findings coincided with the remodeling of the cervical connective tissue.
Stjernholm
Y
Y
Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
Sahlin
L
L
Akerberg
S
S
Elinder
A
A
Eriksson
H A
HA
Malmström
A
A
Ekman
G
G
D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy / Q000378:metabolism / Q000502:physiology*; D011374:Progesterone / Q000097:blood / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012995:Solubility
D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003094:Collagen