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Cited by 139Hormonal and reproductive studiesSperm and Testicular FunctionHypothalamic control of reproductive hormones

Leydig cell aging and hypogonadism

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Beattie, M.C., Adekola, L., Papadopoulos, V., Chen, H., Zirkin, B.R.·2015·Experimental Gerontology
DOI 10.1016/j.exger.2015.02.014PMC PMC5662440
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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.

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  • In men, the decline in C19 steroid production can be explained by simultaneous age-related reductions of both adrenal and testicular androgen biosynthesis.

    “In men, the decline can be explained by simultaneous age-related reductions of both adrenal and testicular androgen biosynthesis (Beattie et al., 2015, Camacho et al., 2013, Golan et al., 2015, Labrie et al., 1997b).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Beattie et al., 2015

  • A decline of androgens in men starting in the third decade of life can be observed as aging results in a gradual development of testicular failure due to a decreased number of Leydig cells and response to hypothalamic-pituitary signalling.

    “A decline of androgens in men starting in the third decade of life can be observed as aging results in a gradual development of testicular failure due to a decreased number of Leydig cells and response to hypothalamic-pituitary signalling (Beattie et al., 2015, Golan et al., 2015).”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Beattie et al., 2015

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Authors
Beattie, M. C., Adekola, L., Papadopoulos, V., Chen, H., & Zirkin, B. R.
Affiliations
  • Johns Hopkins University (US)
  • Research Institute of the McGill University Health Centre (CA)
Corresponding author
Zirkin, B.R.
ORCID
Venue
Experimental Gerontology
Publisher
Elsevier BV
Published
2015-08
Volume
68
Pages
87-91
ISSN
0531-5565 (ISSN-L)
DOI
10.1016/j.exger.2015.02.014
PMC
PMC5662440
OpenAlex
W2056583090
Cited by
139
References
79
Citations by year
2026: 13 · 2025: 16 · 2024: 14 · 2023: 14 · 2022: 20 · 2021: 18 · 2020: 11 · 2019: 8 · 2018: 5 · 2017: 13 · 2016: 3 · 2015: 4
FWCI
1.25
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Gerontology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R37 AG021092, R03 AG026721)
  • Canadian Institutes of Health Research (CIHR MOP125983)
  • Canada Research Chair in Biochemical Pharmacology
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
hypogonadism, testosterone production, steroidogenesis, luteinizing hormone, cAMP signaling, steroidogenic acute regulatory protein, translocator protein (TSPO), smooth endoplasmic reticulum, intracellular redox balance, LH suppression, spermatogenesis, male fertility, prostate tumorigenesis, metabolic syndrome
MeSH terms
Steroidogenic Acute Regulatory Protein, Animals, Humans, Hypogonadism, Leydig Cells, Male, Phosphoproteins, Testosterone, Cellular Senescence, Receptors, GABA, Hormone Replacement Therapy, Rats

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