Adrenomedullary stem cells can instigate the formation of steroidogenic adrenal cortex through paracrine signalling

Yasmine Kemkem; Alice Santambrogio; James Kaufman-Cook; Bence Kover; Miriam Vazquez Segoviano; Olivia Sherwin; Cynthia Andoniadou

doi:10.1530/endoabs.110.P59

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Endocrine Abstracts (2025) 110 P59 | DOI: 10.1530/endoabs.110.P59

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

Adrenomedullary stem cells can instigate the formation of steroidogenic adrenal cortex through paracrine signalling

Yasmine Kemkem ¹ , Alice Santambrogio ^1,2 , James Kaufman-Cook ¹ , Bence Kover ¹ , Miriam Vazquez Segoviano ¹ , Olivia Sherwin ^1,2 & Cynthia Andoniadou ^1,2

Author affiliations

¹King’s College London, London, UK; ²Technical University of Dresden Medical School, Dresden, Germany

JOINT821

Adrenal disorders, such as congenital adrenal hyperplasia or Addison’s disease, can require lifelong hormone replacement therapy and may result in potentially life-threatening complications. Although steroid cell replacement strategies could be attractive therapeutical approaches, the generation of steroid hormone-producing cells in vitro remains inefficient. The adrenal glands consist of two interdependent tissues of distinct developmental origin: the adrenal cortex, which arises from the intermediate mesoderm during development, and the adrenal medulla, which originates from the trunk neural crest, migrating from the neural folds. We recently demonstrated that SOX2+ cells of the postnatal adrenal medulla have stem cell properties throughout life, generate new chromaffin cells, and promote chromaffin cell proliferation through paracrine secretion of WNT6. It is not known if this inductive potential of neural crest-derived adrenomedullary stem cells (AMSCs) extends to the influence of cell fate and regulation in the cortex. We present here that altering the metabolic activity of AMSCs through genetic mutation in the succinate dehydrogenase complex, leads to changes in their paracrine secretion properties. Mutant AMSCs of postnatal mice influence surrounding mesenchyme, leading to the generation of new accessory adrenal structures in vivo, that include a capsule and adrenal cortex expressing steroidogenic markers. These results confirm that postnatal mesenchyme can remain competent to generate new adrenal cortex in vivo, and that key signals, secreted from mutant AMSCs, can influence steroidogenic differentiation. Taken together, these findings can be harnessed to improve the efficiency of regenerative approaches for adrenal disorders relying on the generation of steroid-producing cells.