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Possible link between FSH and RANKL release from adipocytes in men with impaired gonadal function including

Li Juel Mortensen1, Mette Lorenzen2, Niels Jørgensen3

  • 1Group of skeletal, mineral and gonadal endocrinology, University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark; Division of Bone and Mineral Research, HSDM/HMS, Harvard Medical School, Boston, USA.

Bone
|March 28, 2019
PubMed
Abstract

Insights

Follicle-stimulating hormone (FSH) is inversely linked with soluble-RANKL (sRANKL) in men with infertility or Klinefelter syndrome. FSH may directly stimulate RANKL production in adipocytes, suggesting potential roles in metabolic and bone health.

Area of Science:

  • Endocrinology
  • Metabolic Health
  • Bone Biology

Background:

  • The FSH receptor (FSHR) is present in human bone cells and adipocytes.
  • Mouse studies suggest gonadotropins influence glucose, adipocyte, and bone homeostasis.
  • Investigating gonadotropin links to glucose and lipid metabolism in hypergonadotropic men is crucial.

Purpose of the Study:

  • To examine associations between gonadotropins (LH, FSH) and metabolic/bone markers in hypergonadotropic men.
  • To explore FSHR expression and FSH's effect on RANKL in human adipocytes.
  • To clarify potential extra-gonadal roles of FSH.

Main Methods:

  • Cross-sectional study of 307 infertile men and 28 Klinefelter syndrome (KS) men.
  • Measured serum LH, FSH, sRANKL, OPG, osteocalcin, glucose, insulin, sex steroids, and body composition.
  • Investigated FSHR expression and FSH stimulation of RANKL in human adipocyte models (hMADS, TERT-hWA).

Main Results:

  • Serum FSH was not directly linked to glucose/lipid metabolism but inversely associated with sRANKL (p < .05).
  • Elevated FSH in infertile men correlated with lower sRANKL (p = .015).
  • sRANKL positively associated with fat percentage, insulin, and glucose (p < .05); higher in prediabetic men (p = .021).
  • FSHR expressed in adipocytes; FSH treatment increased RANKL release (p < .05).

Conclusions:

  • Hypergonadotropic men with prediabetes show low Inhibin B/testosterone but high RANKL.
  • FSH and sRANKL are inversely associated, with potential direct FSH effects on adipocyte RANKL production.
  • Further research is needed to confirm FSH's role in skeletal RANKL regulation.
Keywords:
AdipocytesGonadotropinsInfertilityPrediabetesRANKL

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