Estradiol Synthesis and Release in Cultured Female Rat Bone Marrow Stem Cells

Dalei Zhang,Ting Zou,Junhong Gao,Lei Wu,Xiaying Lu,Sifan Xu,Jinglei Wang,Bei Yang,Weiying Zou,Mingdi Xiong

doi:10.1155/2013/301540

Abstract

Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17β (E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.

Highlights

Steroid hormones play important regulatory roles in female reproduction, in which estrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells [1,2,3,4]
We demonstrated that female rat Bone marrow stem cells (BMSCs) could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17ββ (E2) under high glucose culture conditions with or without retinoic acid (RA). e cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis
We investigated the effects of RA on BMSC differentiation in vitro. e result showed that the expression of CYP19 mRNA was not further elevated by RA treatment at a concentration of 10−5 mol/L (Figure 1)

Summary

Introduction

Steroid hormones play important regulatory roles in female reproduction, in which estrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells [1,2,3,4]. The total amount of oestrogen synthesized by these extragonadal sites may be small. Within these sites, E2 is probably biologically active only at local tissue level in a paracrine or intracrine fashion without signi cantly affecting circulating levels [6,7,8]. It is difficult to provide an optimal therapeutic dose for long-term estrogen replacement therapy. It is associated with a substantial risk for cardiovascular disease and breast cancer [12]. For this reason, alternative therapies such as steroidogenic cell transplantation may have advantages over

Methods

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Conclusion