Estradiol Reduces Incorporation of Radioactive Sulfate Into Cartilage and Aortas of Rats

Abstract

Hormonal influences on connective tissues have been observed for a variety of hormones and a variety of sites. Gonadal hormones cause accumulation of intercellular ground substance in certain locations; the sex skin of monkeys (1) and the cock's comb (2) are well known examples. The metabolism of sulfated mucopolysaccharide components of connective tissue is known to be influenced by growth hormone (3, 4) and adrenal steroids (5, 6, 7), but only cursory metabolic studies have been reported using sex hormones (8, 9). An attempt has been made to determine whether one gonadal steroid, estradiol, influences the metabolism of connective tissue; and hyaline costal cartilage and aorta were chosen for examination. The incorporation of sulfate labeled with S a5 into these tissues, both in vivo and in vitro, was used as a specific measure of metabolic activity of sulfated mucopolysaccharides. Justification for this view can be found in reports from several laboratories (10-13). Hyaline cartilage was chosen for study because it contains large amounts of chondroitin sulfate and because its response to other hormones is well documented (3-7). Aorta was chosen as an example of arterial connective tissue because the rate of incorporation of sulfate into it is impressive (14) and because some striking sex differences in incidence and severity of arterial disease, both spontaneous and experimentally induced (15-19), have been observed. The metabolism of the mucopolysaccharide components of arteries could conceivably have a bearing upon these differences in incidence of disease. Materials and MethodsAnimals.--All animals used in these experiments were adult rats of the Sprague-Dawley strain initially ranging in weight from 200 to 400 gin., but varying by no more than 20 gin. within any one experiment. These were housed in groups of six and supplied with Purina chow and tap water ad l/b., except where indicated in the text.Hormones and Admlnistratitm.--The following preparations of hormone were used: 1 ml.

Effects of Estrogen and Progestogen Treatment on the Response of the Aorta of Male Rats to Hypertension: MORPHOLOGICAL AND CHEMICAL STUDIES

“…First, both estrogens and progestogens have unpredictable effects on blood pressure in normal man and other animals (24,25), which would add another variable to any study of their effects. This variable was avoided in the present study in view of the similar levels of hypertension attained by groups H, E, and P. Second, the difference in growth rate of the estrogentreated animals was anticipated (12). We have previously shown that the degree of changes in the vessel wall induced by hypertension are so striking that they overwhelm any growth-related differences in vessel wall morphology and chemistry (6,20).…”

“…However, the protective effect does not seem to be wholly explainable by the lipid changes induced by estrogen treatment. The role of vessel wall factors in this protection has been postulated (8,12).…”

Effects of estrogen on cartilage and experimentally induced osteoarthritis

“…The effect does not appear to be a direct one since sulfate incorporation by chondrocytes in tissue (6) or cell (9) culture is not diminished by in vitro exposure to estrogens in the media. The observation that the suppressive effect of estrogens on cartilage requires a 3-day latency period of administration (6) suggests that the action of estrogen on cartilage is in- direct. Estrogen inhibition of somatomedin (sulfation factor) could explain these findings.…”

“…Silberberg and Silberberg ( 4 3 found that male mice genetically predisposed to a high incidence of osteoarthritis had decreased frequency and severity of lesions with estrogen administration. In vivo and in vitro studies after estradiol administration to animals revealed depressed sulfate metabolism in normal rat hyaline costal cartilage (6) and rabbit epiphyseal cartilage (7). Other in vitro studies in which estrogens were added to cell cultures revealed suppression of chondrocyte proliferation (8) and possible stimulation of 35S0, incorporation by these cells (9).…”

Age-Linked Modification of the Effect of Estrogen on Joints and Cortical Bone of Female Mice

“…Loss of mucopolysaccharide from the matrix is often considered as an early if not the primary event in the joint disease [5]. Since estrogen inhibits the production of mucopoly saccharide by chondrocytes [6], the hormone should be expected to promote rather than inhibit the evolution of the lesions. Yet, decreased synthesis of mucopolysaccharides might be counterbalanced by in creased polymerization [7] or linking of MPS with collagen.…”