Comparative study of steroid hormone synthesis in a drug-induced deficiency syndrome by continuous and interval administration of cisplatin in mice
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1.School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. 2. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203

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    Abstract:

    Objective To research the effect of different administration protocols of cisplatin on the biosynthesis and reserve of steroids in mice. Methods Forty female ICR mice were randomly divided into four groups: a cisplatin continuous administration group (CA-group), a cisplatin interval administration group (IA-group), and two corresponding control groups. The CA-group was injected with 3 mg / kg cisplatin for 7 consecutive days. The IA-group was injected with 10 mg / kg cisplatin once per week, for 4 weeks. Rotating-stick, holding power, movements and axillary temperature were examined before the last injection, also the end of laboratory animal model making. The day after, the mice were killed, the visceral organs were separated weighed, included the kidney, heart, thymus and spleen. Relative mRNA expression levels in the hypothalamus (GnRH and CRH), pituitary (Pomc, Fshb, Lhb, and Pou1f1), adrenal and ovary (StAR, Cyp11a1, Cyp21a1, Cyp17a1, Cyp11b1, Hsd3b2, Cyp19a1, Hsd17b1, Esr1, Esr2, and Gper1) tissue were examined by RT-qPCR. Protein expression levels ( StAR, CYP11A1, CYP21A2 and CYP11B1) in adrenal and ovary tissues were examined. Results Compared with the control group, body weight was reduced by cisplatin in two different mouse models. Visceral organs were inhibited and the Qi deficiency syndrome was induced by cisplatin administration. In two different cisplatin models, murine primordial follicles showed accelerated activation and differentiation, and many atretic follicles were produced containing apoptotic granulosa and theca cells. Healthy mature follicle numbers were reduced significantly. There were no detectable changes in adrenal histology. In adrenal tissue, StAR expression was inhibited in the CA-group and upregulated in the IA-group, which also exhibited reduced CYP11B1 protein expression. In the ovary, the expression levels of Cyp11a1, Hsd3b2, Esr1, and Gper1 mRNAs were upregulated and Star and Cyp17a1 mRNA expression was reduced in the CA-group. The expression levels of StAR protein and Hsd3b2 mRNA were decreased in the IA-group. In the hypothalamus, the expression levels of GnRH and CRH mRNAs were reduced in the CA-group. In the pituitary, the expression levels of Pomc, Fshb and Pou1f1 mRNAs were increased in the CA-group, and level of Lhb mRNA was reduced in the IA-group. Conclusions Qi deficiency syndrome and vital essence deficiency syndrome in mice can be induced by cisplatin. The ovary was damaged more significantly and selectivity than the adrenal gland. The functions of the hypothalamus and pituitary were further inhibited by continuous cisplatin injection in the short-term.

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History
  • Received:April 26,2021
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  • Online: December 03,2021
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