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Effect of sex steroids on bone collagen synthesis in vitro

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Summary

Although sex steroids are known to affect skeletal metabolism, their effects on bone collagen synthesis have not been studied. We have examined the direct effects of progesterone, 17β estradiol, testosterone, 5α dihydrotestosterone and dehydroepiandrosterone on bone collagen and noncollagen protein synthesis in cultures of calvaria obtained from 21-day fetal rats. Bones were incubated for 24 to 168 h and3H-proline was added for the last 2 h of culture. Incorporation of the label into collagenase-digestible protein (CDP)1 and noncollagen protein (NCP) was determined using repurified bacterial collagenase.

Progesterone caused a dose dependent inhibition of the labeling of CDP at concentrations of 3×10−7 M to 10−5 M after 96 h of culture. A smaller inhibitory effect was observed on NCP. The inhibitory effect was slow in onset and persisted when bones were incubated for 48 h with progesterone and then transferred to control medium for 48 h. Progesterone also inhibited the incorporation of3H-thymidine and3H-uridine into fetal rat calvaria.

After 24 h of culture, 17β estradiol and testosterone had no effects on the labeling of CDP and NCP. After 96 h, 17β estradiol had a small and inconsistent stimulatory effect on the labeling of CDP but testosterone had no effect. Neither hormone altered the inhibitory effects of parathyroid hormone, cortisol and progesterone. Dihydrotestosterone and dehydroepiandrosterone had no effects after 24 h and 96 h of culture. 17β estradiol, testosterone and dihydrotestosterone did not affect the incorporation of3H-uridine or3H-thymidine into fetal rat calvaria.

Our studies indicate that progesterone is an inhibitor of bone collagen synthesis and estrogens and androgens are not major regulators of bone formation in vitro.

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Abbreviations

BGJ:

chemically defined medium modified from that described by Biggers, Gwatkin and Heyner [2]

CDP:

collagenase-digestible protein

NCP:

noncollagen protein

PTH:

parathyroid hormone

TCA:

trichloracetic acid

DNA:

deoxyribonucleic acid

RNA:

ribonucleic acid

dpm:

disintegrations per minute

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Canalis, E., Raisz, L.G. Effect of sex steroids on bone collagen synthesis in vitro. Calc. Tis Res. 25, 105–110 (1978). https://doi.org/10.1007/BF02010758

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  • DOI: https://doi.org/10.1007/BF02010758

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