Inhibition of Synthesis of Sulfated Mucopolysaccharides by Estradiol

Abstract

The influence of estradiol upon incorporation of isotopes into the sulfated acid mucopolysaccharides of connective tissues of the rat has been studied. Administration of the hormone for 3 weeks significantly reduces the in vitro incorporation of S35-sulfate into cartilage and thoracic aorta without significantly altering the amount of hydrolyzable sulfate in these tissues. The reduction of sulfate incorporation into these tissues by estradiol represents reduced synthesis since the hormone reduces incorporation of sulfate into the acid mucopolysaccharides of the tissue to the same extent and since reduction in incorporation of C14-glucose also parallels S35-sulfate incorporation into acid mucopolysaccharides. The rate of synthesis of sulfated acid mucopolysaccharides is greater in thoracic aorta than abdominal aorta or cartilage. Since the amount of hydrolyzable sulfate is the same in these two portions of aorta, the turnover is also more rapid in the thoracic aorta.

Effects of estrogen on cartilage and experimentally induced osteoarthritis

“…The net result would be minimal change in proteoglycan concentration as observed with Safranin-0 stain in the present study. The studies by Priest and Koplitz (18) and Berntsen (7) support the validity of our observations with the Safranin-0 technique, despite the relative imprecision of the latter method in quantitating proteoglycan concentration. The findings emphasize the need to determine at least two of the variables of uptake, concentration and degradation, for accurate assessment of metabolic changes.…”

“…In actuality, the intensity of Safranin-0 staining in articular cartilage of estrogen treated animals was not diminished. Priest and Koplitz (18) noted that total hydrolyzable sulfate in specimens of costal cartilage under the influence of estrogens remained the same as in controls despite demonstrated decreased "SO, uptake. Similarly, Berntsen (7) noted a concurrent reduction in hexosamine and uronic acid content of only 10-20% despite a 50% decrease in '%O, incorporation in epiphyseal cartilage of immature rabbits receiving estrogen.…”

Metabolism of Cartilage

“…Es tradiol inhibits both glycosaminoglycan and DNA synthesis (Priest and Koplitz, 1962;Dziewiatkowski, 1964;Sokoloff, 1976). Estrogens inhibit growth and accelerate closure of the growth plate, antagonizing growth hormone in these peripheral cartilages, although both hormones work together in regulating body development.…”

Prolonged oestrogen treatment inhibits growth hormone-induced growth in hypopituitary dwarf mice

“…Since oestrogen does not exert any direct inhibitory effect in vitro on cartilage metabolism in somatomedin bioassays (Phillips et al 1975), it would appear that oestrogen affects somatomedin generation rather than inhibiting its actions in peripheral tissues. However, oestrogen treatment in vivo suppresses 35S042~incorporation into cartilage of hypophysectomized rats (Priest & Koplitz, 1962) and inhibits linear growth in hypophysectomized weanling rats (Paesi & de Jong, 1954) in which somatomedin levels would already be very low to negligible. Under these circum¬ stances it is difficult to explain the growth-inhibiting effects of oestrogens on the basis of a suppression of somatomedin generation alone.…”