Effects of Cyclosporin A on sex hormone and estrogen receptor in male rat with special reference to Cyclosporin A-induced osteoporosis

Won Yeong Shin, Song Zhul Li, Sang Su Chung, Hyun Chul Lee, Kab Bum Huh, Sungkil Lim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The mechanisms of high turnover bone loss induced by Cyclosporin A (CsA) are not clearly understood. Deficiencies in sex hormones result in high turnover osteoporosis, and not only androgen but also estrogen plays an important role in maintaining bone mass in men. To study whether or not there are any changes in the levels of sex hormones, aromatization, and the expression of estrogen receptors in CsA-induced osteoporosis, we treated 39 rats with vehicle, low-dose CsA (5 mg/kg) and high dose CsA (15 mg/kg) for 28 days, and measured sex hormone levels by radioimmunoassay. Aromatase activities in ROS cells and 3T3-L1 cells were determined by measuring the conversion rate of 3 H-androstenedione into 3 H-estrone. ER and ER mRNA were measured by competitive RT-PCR in collected marrow cells and ROS cells. The levels of free testosterone in the serum in low-dose CsA-treated rats were unchanged, but the levels were significantly decreased in those treated with high-dose CsA as previously reported. The levels of total estradiol in the serum were significantly increased in the low-dose CsA-treated group (5 mg/kg) and were comparable to levels of the control group in the high-dose CsA-treated group (15 mg/kg). CsA increased the conversion of 3 H- androstenedione to 3 H-estrone in ROS cells, but not in 3T3-L1 cells. Meanwhile, CsA treatment did not change the rates of ER or ER mRNA expression in ROS cells or in collected bone marrow cells. In conclusion, CsA treatment decreased the level of free testosterone in the serum, but did not decrease the level of serum estradiol by enhancing aromatization. High-turnover osteoporosis induced by clinical dosage CsA treatment may not be caused by lowering the levels of circulating estrogen or by decreasing the expression of estrogen receptors.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalYonsei medical journal
Volume41
Issue number1
DOIs
Publication statusPublished - 2000 Jan 1

Fingerprint

Gonadal Steroid Hormones
Estrogen Receptors
Cyclosporine
Osteoporosis
3T3-L1 Cells
Androstenedione
Estrone
Serum
Testosterone
Estradiol
Estrogens
Messenger RNA
Aromatase
Bone Remodeling
Bone Marrow Cells
Androgens
Radioimmunoassay
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Shin, Won Yeong ; Li, Song Zhul ; Chung, Sang Su ; Lee, Hyun Chul ; Huh, Kab Bum ; Lim, Sungkil. / Effects of Cyclosporin A on sex hormone and estrogen receptor in male rat with special reference to Cyclosporin A-induced osteoporosis. In: Yonsei medical journal. 2000 ; Vol. 41, No. 1. pp. 61-67.
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abstract = "The mechanisms of high turnover bone loss induced by Cyclosporin A (CsA) are not clearly understood. Deficiencies in sex hormones result in high turnover osteoporosis, and not only androgen but also estrogen plays an important role in maintaining bone mass in men. To study whether or not there are any changes in the levels of sex hormones, aromatization, and the expression of estrogen receptors in CsA-induced osteoporosis, we treated 39 rats with vehicle, low-dose CsA (5 mg/kg) and high dose CsA (15 mg/kg) for 28 days, and measured sex hormone levels by radioimmunoassay. Aromatase activities in ROS cells and 3T3-L1 cells were determined by measuring the conversion rate of 3 H-androstenedione into 3 H-estrone. ER and ER mRNA were measured by competitive RT-PCR in collected marrow cells and ROS cells. The levels of free testosterone in the serum in low-dose CsA-treated rats were unchanged, but the levels were significantly decreased in those treated with high-dose CsA as previously reported. The levels of total estradiol in the serum were significantly increased in the low-dose CsA-treated group (5 mg/kg) and were comparable to levels of the control group in the high-dose CsA-treated group (15 mg/kg). CsA increased the conversion of 3 H- androstenedione to 3 H-estrone in ROS cells, but not in 3T3-L1 cells. Meanwhile, CsA treatment did not change the rates of ER or ER mRNA expression in ROS cells or in collected bone marrow cells. In conclusion, CsA treatment decreased the level of free testosterone in the serum, but did not decrease the level of serum estradiol by enhancing aromatization. High-turnover osteoporosis induced by clinical dosage CsA treatment may not be caused by lowering the levels of circulating estrogen or by decreasing the expression of estrogen receptors.",
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Effects of Cyclosporin A on sex hormone and estrogen receptor in male rat with special reference to Cyclosporin A-induced osteoporosis. / Shin, Won Yeong; Li, Song Zhul; Chung, Sang Su; Lee, Hyun Chul; Huh, Kab Bum; Lim, Sungkil.

In: Yonsei medical journal, Vol. 41, No. 1, 01.01.2000, p. 61-67.

Research output: Contribution to journalArticle

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