Leydig cells: formation, function, and regulation

Biol Reprod · 2018 · Unclear · Insufficient evidence

← Research stream

UnclearInsufficient evidencePaper 6835

Study snapshot

PublicationBiol Reprod · 2018

Study typereview

Reported directionUnclear

Evidence ratingInsufficient

Abstract

Herein we summarize important discoveries made over many years about Leydig cell function and regulation. Fetal Leydig cells produce the high levels of androgen (testosterone or androstenedione, depending upon the species) required for differentiation of male genitalia and brain masculinization. Androgen production declines with loss of these cells, reaching a nadir at postpartum. Testosterone then gradually increases to high levels with adult Leydig cell development from stem cells. In the adult, luteinizing hormone (LH) binding to Leydig cell LH receptors stimulates cAMP production, increasing the rate of cholesterol translocation into the mitochondria. Cholesterol is metabolized to pregnenolone by the CYP11A1 enzyme at the inner mitochondrial membrane, and pregnenolone to testosterone by mitochondria and smooth endoplasmic reticulum enzymes. Cholesterol translocation to the inner mitochondrial membrane is mediated by a protein complex formed at mitochondrial contact sites that consists of the cholesterol binding translocator protein, voltage dependent anion channel, and other mitochondrial and cytosolic proteins. Steroidogenic acute regulatory protein acts at this complex to enhance cholesterol movement across the membranes and thus increase testosterone formation. The 14-3-3γ and ε adaptor proteins serve as negative regulators of steroidogenesis, controlling the maximal amount of steroid formed. Decline in testosterone production occurs in many aging and young men, resulting in metabolic and quality-of-life changes. Testosterone replacement therapy is widely used to elevate serum testosterone levels in hypogonadal men. With knowledge gained of the mechanisms involved in testosterone formation, it is also conceivable to use pharmacological means to increase serum testosterone by Leydig cell stimulation.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typereview

Effect directionunclear

PopulationFetal and adult Leydig cells; men with declining testosterone/hypogonadism discussed in review context

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthInsufficientConfidence: 98% · Peer reviewed: yes

Main findings

This review summarizes discoveries on Leydig cell development, function, and regulation. It describes fetal and adult Leydig cell roles in androgen production, the LH/cAMP-driven steroidogenic pathway, mitochondrial cholesterol transport mechanisms, and factors regulating testosterone synthesis, while noting testosterone decline in some aging and young men and discussing replacement therapy and possible pharmacological stimulation of Leydig cells.

Outcomes measured

Leydig cell formation and development
Androgen/testosterone production
Regulation of steroidogenesis
LH receptor/cAMP signaling
Cholesterol translocation into mitochondria
Aging-related decline in testosterone
Testosterone replacement therapy

Limitations

Narrative review rather than a primary study
No EMF exposure assessed in the abstract
No sample size reported in the abstract
No quantitative effect estimates reported in the abstract

View raw extracted JSON

{
  "study_type": "review",
  "exposure": {
    "band": null,
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Fetal and adult Leydig cells; men with declining testosterone/hypogonadism discussed in review context",
  "sample_size": null,
  "outcomes": [
    "Leydig cell formation and development",
    "Androgen/testosterone production",
    "Regulation of steroidogenesis",
    "LH receptor/cAMP signaling",
    "Cholesterol translocation into mitochondria",
    "Aging-related decline in testosterone",
    "Testosterone replacement therapy"
  ],
  "main_findings": "This review summarizes discoveries on Leydig cell development, function, and regulation. It describes fetal and adult Leydig cell roles in androgen production, the LH/cAMP-driven steroidogenic pathway, mitochondrial cholesterol transport mechanisms, and factors regulating testosterone synthesis, while noting testosterone decline in some aging and young men and discussing replacement therapy and possible pharmacological stimulation of Leydig cells.",
  "effect_direction": "unclear",
  "limitations": [
    "Narrative review rather than a primary study",
    "No EMF exposure assessed in the abstract",
    "No sample size reported in the abstract",
    "No quantitative effect estimates reported in the abstract"
  ],
  "evidence_strength": "insufficient",
  "confidence": 0.98,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "Leydig cells",
    "testosterone",
    "androgen production",
    "steroidogenesis",
    "luteinizing hormone",
    "cAMP",
    "cholesterol translocation",
    "mitochondria",
    "CYP11A1",
    "steroidogenic acute regulatory protein",
    "hypogonadism",
    "testosterone replacement therapy"
  ],
  "suggested_hubs": []
}

AI can be wrong. Always verify against the paper.

AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1093/biolre/ioy059
PubMed: 29566165

Read the original paper →

Related papers

← Back to the Research Library