Pharmacological actions of 17β-oestradiol on articular cartilage chondrocytes and chondrosarcoma chondrocytes in the absence of oestrogen receptors

Abstract

(1) Pharmacological concentrations (greater than 10 −5 M) of 17β-oestradiol inhibited 35S-labelled proteoglycan synthesis in bovine articular cartilage explant cultures. They also inhibited 35S-labelled proteoglycan synthesis and 3H-labelled protein synthesis in cell cultures of chondrocytes from bovine articular cartilage and Swarm rat chondrosarcoma. Maximal inhibition was about 30–50%. Physiological concentrations (10 −9−10 −8 M) of oestradiol had no effect on the synthesis of either protein or proteoglycan. (2) The inhibitory action of high concentrations of oestradiol on these biosynthetic pathways is not common to all steroids since 10 −4 M cortisol had no effect on articular chondrocyte cell cultures. 10 −4 M testosterone had a similar action to oestradiol. (3) Neither physiological nor pharmacological concentrations of 17β-oestradiol had any effect on 35S-labelled proteoglycan turnover in the cartilage explant system. (4) 10 −5 M oestradiol inhibited cell division in cultures of articular chondrocytes which had entered the log growth phase. 10 −7 M oestradiol had no effect on articular chondrocyte growth. (5) In male rats implanted with silastic capsules releasing 17β-oestradiol, increase in body weight was retarded by about 25% over a period of 6 weeks, compared to control rats. Rat chondrosarcoma grew to the same size in oestrogen-treated rats as it did in controls. (6) Oestrogen receptors could not be detected in freshly isolated bovine articular chondrocyctes or in rat chondrosarcoma. (7) In conclusion, neither the mitotic rate of articular chondrocytes nor their proteoglycan metabolism is under the direct physiological control of oestradiol. Growth and biosynthetic activity of the rat chondrosarcoma chondrocytes are independent of either direct control by the hormone or control effected by oestradiol regulation of a second hormone or growth factor.