title: Leydig cell aging and hypogonadism.
abstract: Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Beattie
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Adekola
authors.affiliation: The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Biochemistry and Pharmacology, McGill University, Montreal, Quebec, Canada; Department of Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulos
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: brzirkin@jhu.edu.
authors.forename: B R
authors.initials: BR
authors.lastname: Zirkin
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007985:Leydig Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism / Q000502:physiology; D013739:Testosterone / Q000378:metabolism / Q000627:therapeutic use; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D018079:Receptors, GABA; C499229:TSPO protein, human; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone
keywords: Aging; Hypogonadism; TSPO; Testosterone