SF‐1/Ad4BP transforms primary long‐term cultured bone marrow cells into ACTH‐responsive steroidogenic cells

Abstract

Bone marrow stem cells develop into haematopoietic and mesenchymal lineages, but have not been known to participate in steroidogenic cell production. Steroidogenic factor 1 (SF-1), also designated adrenal 4 binding protein (Ad4BP), is an essential orphan nuclear receptor for steroidogenesis as well as for adrenal and gonadal gland development. In the present study, we revealed that the adenovirus-mediated forced expression of SF-1 can transform cultured primary long-term cultured bone marrow cells into steroidogenic cells, showing the de novo synthesis of multiple steroid hormones in response to adrenocorticotropic hormone (ACTH). This finding may provide an initial step in innovative autograft cell transfer therapy for steroid hormone deficiencies.

Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells

“…To test the capability for osteoblastic differentiation, 4 . 5!10 4 cells were plated on 35 mm dish, cultured in NH OsteoDiff medium (Miltenyi Biotec) for 10 days and stained with alkaline phosphatase (Gondo et al 2004). Adipogenic differentiation was confirmed at a cell density of 7 .…”

“…A recombinant adenovirus vector derived from the human type 5 adenovirus using a commercially available Adenovirus Expression Vector Kit (TakaraBio Ltd, Shiga, Japan), containing bovine SF-1 cDNA (AdxbSF-1) or LacZ cDNA (Adx-LacZ) as a control, and was prepared as previously described (Gondo et al 2004). Full-length human cDNAs for SF-1, WT1, DAX-1, PBX-1, CITED2, and WNT4 were cloned by reverse transcriptase-polymerase chain reaction (RT-PCR) using appropriate tissue total RNA with primers based on the GenBank database, subcloned into pCR-Blunt II-TOPO vector (Invitrogen) and then the entire sequences of these constructs were verified by sequencing.…”

“…Therefore, we tested whether the introduction of SF-1 into mouse BMCs could produce steroidogenic cells (Gondo et al 2004). We expanded a relatively pure BMC population by culturing the cells for 120-180 days, and then demonstrated that adenovirus-mediated forced expression of SF-1 in long-term cultured BMCs can produce steroidogenic cells with the capacity for de novo synthesis of various steroid hormones in response to adrenocorticotropic hormone (ACTH).…”

Management Approaches to Congenital Adrenal Hyperplasia in Adolescents and Adults; Latest Therapeutic Developments

“…Despite their shortcomings, the use of adult stem cells benefits from a longer investigational track record and avoids ongoing political issues with the use of fetal stem cells. Yazawa et al have reported that human MSC's transfected with SF-1, a transcription factor required for both adrenal and gonadal steroidogenesis, differentiate into cortisol producing cells rather than androgen producing cells when transplanted into mouse testis, while Gondo et al reported that such cells were ACTH-responsive (Yazawa et al, 2006;Gondo et al, 2004). Another approach is that of Hammer et al who characterized a subpopulation of adrenal cells that are typically dormant or undifferentiated.…”

Identification of a novel melanocortin 2 receptor splice variant in murine adipocytes: implications for post-transcriptional control of expression during adipogenesis

“…Testicular expression declines markedly after birth in the mouse and is barely detectable in the adult. Other reported sites of extra-adrenal expression, include human skin (Slominski et al 1996), sympathetic ganglia (Nankova et al 2003), the pituitary (Morris et al 2003), bone marrow (Gondo et al 2004), osteoblasts and osteoclasts (Zhong et al 2005).…”