Connective Tissue XII. Stimulating Effects of Estrogens on Collagen Synthesis in Rat Uterine Slices. ∗

Abstract

Summary

1. The effect of estradiol, es-trone, estriol and progesterone on collagen and noncollagenous protein (NCP) synthesis was studied in ovariectomized and normal rats both in vivo and in vitro with the Kao uterine slice technique. Both chemical and C¹⁴-lysine determinations were made.

2. Chemical studies revealed that: (a) Of the agents used, estradiol was most effective in stimulating the synthesis of collagen and NCP in the uteri of ovariectomized rats. Estrone, estriol and progesterone were similarly effective, but to a lesser degree. Estradiol also increased the collagen and NCP of normal rats. In the dosages employed, the uteri of estradiol-treated ovariectomized rats showed a greater capacity for synthesizing collagen than did the uteri of normal control rats, (b) After ovariectomy, there was a decrease in uterine weight, total collagen and NCP and an increase in concentration of collagen and NCP. (c) Administration of estrogen to the ovariectomized rat was associated with an increase in uterine weight, and in total amount per uterus of collagen, NCP and supernatant protein (SP). Simultaneously, the concentration of collagen decreased, while that of NCP and SP increased slightly.

3. Considered in conjunction with the chemical analyses, the radioisotopic studies with C¹⁴-lysine revealed that the major effects on uterine connective tissue of estrogen injections into ovariectomized animals as determined in KUST preparations were: (a) A 400%-700% increase in specific activity of collagen and a 50% increase in specific activity of NCP; (b) A 100% increase in total counts per minute recovered in collagen and a 50-60% increase in those of NCP per incubation; (c) a 700% increase in counts per minute in collagen and 200-300% increase in NCP per uterus; (d) A much higher ratio of specific activity of hydroxlysine from the treated rat to that from the untreated rat as compared with the ratio of specific activities of lysine from the same 2 groups of animals; (e) An effective dose of estradiol for stimulation of collagen synthesis is 1 μg with a dose-response time of 16 hours.

4. It is suggested that one of the important, if not the most important, action of estrogen in uterine connective tissue is concerned with the hydroxylation of lysine.

The authors gratefully acknowledge suggestions and advice of Dr. C. R. Treadwell.