Regulation of collagen dissolution in the human uterine cervix

Wallis, Robert M (1980) Regulation of collagen dissolution in the human uterine cervix. University of Southampton, Doctoral Thesis.

Abstract

Collagen dissolution in the non-pregnant human uterine cervix was investigated by following the spontaneous release of hydroxyproline containing peptides from tissue explants into the surrounding culture medium. Typically, the release of these peptides was low during early days of culture and then increased until at least day 18. Progesterone and oestradiol-17 A significantly inhibited collagen dissolution. The latter was only effective if the tissue was maintained in a low oestrogen containing environment, suggesting the oestrogen receptor may be 'labile'. It is therefore concluded that the integrity of the connective tissue framework of the human cervix could be in part under steroid hormone control. Prostaglandins are used clinically to soften the human cervix, but neither PGE2 or Pr~F2 had a significant effect on collagen breakdown. Arachidonic acid, however, was a potent stimulant of collagen dissolution, the action of which was not blocked by indomethacin at concentrations that inhibit prostaglandin synthesis; possible mechanisms of action of arachidonic acid are discussed. Drugs which inhibit prostaglandin synthetase such as indomethacin and meclofenamic acid inhibit collagen dissolution, but only with concentrations greater than that required to inhibit prostaglandin synthesis. In culture cervix explants synthesise PGE, PGF and 6 keto PGFla. The synthesis of these prostanoids could not be positively correlated with the profile for collagen breakdown. It is therefore concluded that it appears unlikely that prostaglandins soften the cervix in vivo by a direct stimulation of collagen breakdown, but changes in the collagen framework mediated by other mechanisms cannot be excluded. In the rat, the softness of the cervix was positively correlated with the degree of acid solubility of collagen. Arachidonic acid, administered on day 18 of pregnancy, softened the cervix, increased the collagen solubility and decreased the collagen concentration. It is therefore possible that this drug softens the cervix in vivo by enhanced enzymatic collagen degradation, this may be mediated by collagenase or other proteases. From this and other studies collagenolytic enzymes appear to have a role in cervix softening, although the interrelationship between these enzymes and other biochemical changes, such as altered glycosaminoglycans, requires determination.

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