Adipose Tissue-Derived and Bone Marrow-Derived Mesenchymal Cells Develop into Different Lineage of Steroidogenic Cells by Forced Expression of Steroidogenic Factor 1

Abstract

Steroidogenic factor 1 (SF-1)/adrenal 4 binding protein is an essential nuclear receptor for steroidogenesis, as well as for adrenal and gonadal gland development. We have previously clarified that adenovirus-mediated forced expression of SF-1 can transform long-term cultured mouse bone marrow mesenchymal cells (BMCs) into ACTH-responsive steroidogenic cells. In the present study, we extended this work to adipose tissue-derived mesenchymal cells (AMCs) and compared its steroidogenic capacity with those of BMCs prepared from the identical mouse. Several cell surface markers, including potential mesenchymal cell markers, were identical in both cell types, and, as expected, forced expression of SF-1 caused AMCs to be transformed into ACTH-responsive steroidogenic cells. However, more elaborate studies revealed that the steroidogenic property of AMCs was rather different from that of BMCs, especially in steroidogenic lineage. In response to increased SF-1 expression and/or treatment with retinoic acid, AMCs were much more prone to produce adrenal steroid, corticosterone rather than gonadal steroid, testosterone, whereas the contrary was evident in BMCs. Such marked differences in steroidogenic profiles between AMCs and BMCs were also evident by the changes of steroidogenic enzymes. These novel results suggest a promising utility of AMCs for autologous cell regeneration therapy for patients with steroid insufficiency and also a necessity for appropriate tissue selection in preparing mesenchymal stem cells according to the aim. The different steroidogenic potency of AMCs or BMCs might provide a good model for the clarification of the mechanism of tissue- or cell-specific adrenal and gonadal steroidogenic cell differentiation.

Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1

“…As is the case for BM-MSCs, MSCs derived from other tissues can be differentiated into steroidogenic cells using the above methods (Gondo et al, 2008;Wei et al, 2012;Yazawa et al, 2014;Yazawa et al, 2010). However, these methods are not applicable to pluripotent stem cells, such as ES cells, iPS cells, and embryonal carcinoma cells, because SF-1 and LRH-1 are cytotoxic to these cells Yazawa et al, 2006).…”

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

“…In recent years, several studies attempted to produce cells resembling adrenocortical cells from human and murine cell sources. The cells of origin comprised embryonic or bone marrow-derived stem cells (including induced 'iPS' from fibroblasts), as well as mesenchymal cells derived from adipose tissue or umbilical cord R131 Review E H Gan and S H Pearce Regenerative medicine in AAD www.eje-online.org (112,113,114,115,116,117,118,119,120). Although these cell sources demonstrated their capability to be reprogrammed to steroidogenic phenotypes by the overexpression of SF1 and cAMP treatment, none fully resembled adrenocortical cells with a complete endogenous steroid profile.…”

The Stromal Contribution to the Development of Resistance to New-Generation Drugs by Castration-Resistant Prostate Cancer

“…Bone overgrowth at metastatic sites causes pain, fracture and spinal cord compression in patients. It has already been demonstrated that bone mesenchymal cells can be differentiated into steroidogenic cells (13) by overexpression of steroidogenic factor-1 (SF), and that SF-1 is a Hh target gene in Leydig cell differentiation (14). Furthermore, enzymes for androgen production are highly expressed in bone core metastases samples (15 .…”