Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury
Nature Medicine 24, 239 (2018).
doi:10.1038/nm.4470
Authors: Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos, Shieh Jae-Hung, Lauren F Young, Amina Lazrak, Odette M Smith, Sophie Lieberman, Fabiana Kreines, Yusuke Shono, Tobias Wertheimer, Robert R Jenq, Alan M Hanash, Prema Narayan, Zhenmin Lei, Malcolm A Moore, Hans-Peter Kiem, Marcel R M van den Brink & Jarrod A Dudakov
There is a substantial unmet clinical need for new strategies to protect the hematopoietic stem cell (HSC) pool and regenerate hematopoiesis after radiation injury from either cancer therapy or accidental exposure. Increasing evidence suggests that sex hormones, beyond their role in promoting sexual dimorphism, regulate HSC self-renewal, differentiation, and proliferation. We and others have previously reported that sex-steroid ablation promotes bone marrow (BM) lymphopoiesis and HSC recovery in aged and immunodepleted mice. Here we found that a luteinizing hormone (LH)-releasing hormone antagonist (LHRH-Ant), currently in wide clinical use for sex-steroid inhibition, promoted hematopoietic recovery and mouse survival when administered 24 h after an otherwise-lethal dose of total-body irradiation (L-TBI). Unexpectedly, this protective effect was independent of sex steroids and instead relied on suppression of LH levels. Human and mouse long-term self-renewing HSCs (LT-HSCs) expressed high levels of the LH/choriogonadotropin receptor (LHCGR) and expanded ex vi...
Source: Nature Medicine - Category: General Medicine Authors: Enrico Velardi Jennifer J Tsai Stefan Radtke Kirsten Cooper Kimon V Argyropoulos Shieh Jae-Hung Lauren F Young Amina Lazrak Odette M Smith Sophie Lieberman Fabiana Kreines Yusuke Shono Tobias Wertheimer Robert R Jenq Alan M Hanash Prema Narayan Zhenmin Le Tags: Letter Source Type: research
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