Projects per year
Abstract / Description of output
Leydig cell number and function decline as men age, and low testosterone is associated with all "Western" cardio-metabolic disorders. However, whether perturbed androgen action within the adult Leydig cell lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which androgen receptor (AR) is ablated from ∼75% of adult Leydig stem cell/cell progenitors, from fetal life onward (Leydig cell AR knockout mice), permitting interrogation of the specific roles of autocrine Leydig cell AR signaling through comparison to adjacent AR-retaining Leydig cells, testes from littermate controls, and to human testes, including from patients with complete androgen insensitivity syndrome (CAIS). This revealed that autocrine AR signaling is dispensable for the attainment of final Leydig cell number but is essential for Leydig cell maturation and regulation of steroidogenic enzymes in adulthood. Furthermore, these studies reveal that autocrine AR signaling in Leydig cells protects against late-onset degeneration of the seminiferous epithelium in mice and inhibits Leydig cell apoptosis in both adult mice and patients with CAIS, possibly via opposing aberrant estrogen signaling. We conclude that autocrine androgen action within Leydig cells is essential for the lifelong support of spermatogenesis and the development and lifelong health of Leydig cells.-O'Hara, L., McInnes, K., Simitsidellis, I., Morgan, S., Atanassova, N., Slowikowska-Hilczer, J., Kula, K., Szarras-Czapnik, M., Milne, L., Mitchell, R. T., and Smith, L. B. Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men.
Original language | English |
---|---|
Pages (from-to) | 894-910 |
Journal | The FASEB Journal |
Volume | 29 |
Issue number | 3 |
Early online date | 17 Nov 2014 |
DOIs | |
Publication status | Published - Mar 2015 |
Fingerprint
Dive into the research topics of 'Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men'. Together they form a unique fingerprint.Projects
- 2 Finished
-
Genetic and Hormonal determinants of male reporoductive health and fertility.
Smith, L.
1/10/11 → 30/09/16
Project: Research
Profiles
-
Laura O'Hara
- Centre for Discovery Brain Sciences
- Deanery of Biomedical Sciences - Lecturer (Zhejiang)
- Edinburgh Neuroscience
Person: Academic: Research Active , Academic: Research Active (Research Assistant)