Regulation of Cartilage Acid Hydrolases by Growth Hormone*

Hubbard, John R.; Liberti, J.P.

doi:10.1210/endo-110-5-1483

Cited by 7 publications

(2 citation statements)

References 16 publications

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“…In addition, WEISSMANN et al (23) showed that lysosomal lysates injected into joints stimulated cartilage cell proliferation. Our finding that growth hormone, a very potent stimulator of cartilage growth, enhanced nonspecific protease activity (7), as well as cartilage cathepsin D and acid phosphatase activities (20) of Hx rat cartilage also supports this contention. It must be emphasized, however, that we have no evidence if the modulation of lysosomal enzymes is a cause or consequence of growth.…”

Section: Discussionsupporting

confidence: 73%

“…The hormone(s) which may be involved in this developmental phenomenon are yet to be explored. However, we have recently shown that growth hormone enhances cathepsin D and acid phosphatase in cartilage of Hx rats (20). Since growth hormone secretion appears to diminish with age (21,22), the initial decline in cartilage cathepsin D and acid phosphatase activities with age could be related in part to their growth hormone-dependence.…”

Section: Discussionmentioning

confidence: 95%

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Alteration of Cartilage Lysosomal Enzyme Activities during Development. (acid hydrolases/cartilage development/cartilage growth/hypophysectomy)

Hubbard¹,

Liberti²

1982

Dev Growth Differ

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Cartilage cathepsin D, cathepsin B and acid phosphatase activities decreased with maturation of Sprague-Dawley rats. Although this phenomenon may largely be due to an age-dependent decrease in cell concentration at young ages (1-8 weeks), in older (8-25 weeks) rats there appeared to be a decrease in enzyme activity per cell.' The dimunition in cartilage cathepsin D activity coincided with an apparent decrease in its concentration. In addition, the inverse correlation between rat age and cartilage lysosomal enzyme activities was, at least in part, tissue specific as the pattern of liver lysosomal enzyme activities was quite different from that noted with cartilage. Interestingly, hypophysectomy greatly diminished age-related modulations in lysosomal enzyme activities suggesting that one or more pituitary hormones may be involved in the mechanism of this age-dependent phenomenon. In addition, cartilage grow;h rate appeared to be correlated with the level of cartilage lysosomal enzyme activities, indicating that these enzymes may be related to the biochemical mechanism of cartilage growth and development.Lysosomes contain many degradative enzymes which function optimally at acidic pH. Although these enzymes were first thought to be involved in cell autolysis, it is becoming increasingly apparent that they may play vital roles in the biochemical mechanism of many normal and pathological processes (1, 2).Developmental changes in lysosomal enzymes have been examined primarily .in liver (3, 4) and cardiac (5) tissues. Cartilage lysosomal enzymes have been highly studied with regard to certain pathological disorders such as osteoarthritis (6). However, age-related perturbations of cartilage lysosomal enzymes have not been well characterized. Examination of cartilage lysosomal enzyme changes with age could lead to important insights regarding the mechanism of cartilage growth, development and pathology.Recently, we found that a nonspecific cartilage acid protease activity was age-dependent (7). The primary purpose of the present investigation was to characterize developmental changes of specific lysosomal enzymes in rat cartilage. Our results show that cartilage (but not liver) cathepsin D, acid phosphatase, and cathepsin B activities decrease with age. In addition, these alterations in enzyme activities were significantly depressed in hypophysectomized rats suggesting that one or more pituitary hormones may be involved in the mechanism of these age-related metabolic changes.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 95%

Alteration of Cartilage Lysosomal Enzyme Activities during Development. (acid hydrolases/cartilage development/cartilage growth/hypophysectomy)

Hubbard¹,

Liberti²

1982

Dev Growth Differ

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Influence of proteinase inhibitors on glucocorticoid receptor properties: recent progress and future perspectives

Hubbard

Kalimi

1985

Mol Cell Biochem

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Effect of steroid hormones on endotoxin-mediated cartilage degradation

et al. 1988

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Cartilage degradation is a characteristic feature of various types of human arthritis, notably rheumatoid arthritis and osteoarthritis. The influence of glucocorticoid and other steroid hormones on cartilage proteoglycan breakdown was examined in a model system in which breakdown is readily quantified by the release of proteoglycan from cultured bovine nasal cartilage discs. Endotoxin (bacterial lipopolysaccharides) treatment enhanced the depletion of cartilage proteoglycan by 2-3 fold. This was inhibited in a concentration-dependent manner by hydrocortisone (10(-9) to 10(-5) M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 x 10(-7) M) after 4 days from endotoxin-treated cultures resulted in the rapid restoration of an endotoxin response, so that proteoglycan release approached maximum levels during a second 4-day culture period. Other C-21 steroid hormones (progesterone, aldosterone) were also inhibitory at 10(-5) M, but testosterone and beta-estradiol showed little influence on endotoxin action. Proteoglycan products of smaller average mol wt (Sepharose CL-2B chromatography), consistent with core protein cleavages, were released from endotoxin-treated cartilage. Cleavage was unaffected by beta-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.

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Regulation of Cartilage Acid Hydrolases by Growth Hormone*

Cited by 7 publications

References 16 publications

Alteration of Cartilage Lysosomal Enzyme Activities during Development. (acid hydrolases/cartilage development/cartilage growth/hypophysectomy)

Alteration of Cartilage Lysosomal Enzyme Activities during Development. (acid hydrolases/cartilage development/cartilage growth/hypophysectomy)

Influence of proteinase inhibitors on glucocorticoid receptor properties: recent progress and future perspectives

Effect of steroid hormones on endotoxin-mediated cartilage degradation

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