Androgen-regulated cervical ripening: a structural, biomechanical, and molecular analysis.
OBJECTIVE
Androgens regulate biomechanical responses in load-bearing tissues. Evidence suggests that androgens may play a role in the cervix. We hypothesized that androgens directly regulate cervical remodeling by altering both collagen structure and proteoglycan composition.


METHODS
Cervical resistance was evaluated using the cervical creep method after the administration of intravaginal dihydrotestosterone or oral flutamide. Microstructural changes in collagen were evaluated by transmission electron microscopy and polarized light birefringence. Proteoglycan expression was evaluated by reverse transcription-polymerase chain reaction for the core proteins (decorin, biglycan, fibromodulin, aggrecan, versican) and fluorophore-assisted carbohydrate analysis.


RESULTS
Dihydrotestosterone decreased cervical resistance, whereas flutamide inhibited the decline in cervical resistance, compared with vehicle controls. Flutamide was associated with higher levels of organized collagen and increased aggrecan expression with a greater proportion of chondroitin/dermatan sulfate glycosaminoglycans. Flutamide inhibited the increase in hyaluronan.


CONCLUSIONS
Androgens appear to play a role in regulating cervical resistance by altering proteoglycan content. Structural analysis indicates that flutamide may alter collagen fibril organization and/or structure.
Ji
Huiling
H
Section of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Women and Infants' Hospital of Rhode Island, Brown University, Providence, RI, USA.
Dailey
Tanya L
TL
Long
Vit
V
Chien
Edward K
EK
D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D020070:Cervical Ripening / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002584:Cervix Uteri / Q000737:chemistry* / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D005865:Gestational Age; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008859:Microscopy, Polarization; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D011509:Proteoglycans; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D005485:Flutamide; D006820:Hyaluronic Acid; D003094:Collagen; D020778:Matrix Metalloproteinase 2