Collagen Synthesis and Degradation in the Uterine Deciduoma: Regulation of Collagenase Activity by Progesterone

Abstract

During the hypertrophic growth associated with the trauma-induced deciduoma in the rat uterus, the collagen content of the traumatized horn increases approximately five-fold. The time course of the accumulation of collagen parallels that of the gain in wet weight of the horn, occurring between the second and eighth post-trauma day. No change in collagen content is measurable in the control, nontraumatized horn of the uterus. All the collagen in the decidualized horn is found to be in the myometrium; none is present in the decidual tissue which accumulates during deciduoma formation.On approximately the ninth post-trauma day the traumatized horn begins to involute, and the collagen content begins to decline. Concomitant with the drop of the collagen content, collagenase activity appears in tissue. No collagenase activity is detectable in the uterus during the period of collagen accumulation. The absence of collagenase in the growing uterus horn indicates that, in this tissue at least, collagen synthesis occurs in the absence of concomitant fibrillar collagen degradation. Collagenase activity is never detectable in the control, contralateral uterine horn. The resorption process lasts approximately four days; by the thirteenth post-trauma day the collagen content has returned to normal and collagenase activity is no longer detectable in the tissue. The level of low-molecular weight (>10,000 dalton) hydroxyproline-containing peptides increases markedly in the traumatized uterine horn, only during the period of collagen synthesis. These levels return to pre-trauma levels before significant collagen resorption occurs, suggesting the possibility that, during uterine growth, collagen turnover occurs at a time prior to the deposition of molecules onto fibrils.Explant cultures of the resorbing deciduomatous uterine horn produce and release collagenase into the culture medium. This production of collagenase is effectively and selectively prevented by the addition of progesterone (2.5 X 10-5M) or the potent synthetic progesterone analogue, medroxyprogesterone acetate (1 X 10-6M). Addditionally, dibutyryl cyclic AMP (10-3M) and theophylline 5 X 10-3M) partially inhibit the production of collagenase by the uterine tissue. Simultaneous addition of progesterone and either dibutyryl cyclic AMP or theophylline results in synergistic inhibition of collagenase production. These findings in the deciduomatous uterus support the concept that progesterone plays an important role in the regulation of collagenase in the uterus and that cyclic AMP potentiates in some way the action of the steroid.