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ER-depletion lowering the 'hypothalamus-uterus-kidney' axis functions by perturbing the renal ERβ/Ptgds signalling

Yan-Ru Liu1, Zhi-Shu Tang1, Jin-Ao Duan2

  • 1Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712083, P.R. China.

Aging
|November 12, 2019
PubMed

Insights

Estrogen receptor depletion accelerates aging in the hypothalamus-uterus-kidney axis, leading to kidney dysfunction and cognitive decline in menopausal syndrome models.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Gerontology

Background:

  • Estrogen decline is linked to menopausal syndromes, but its direct causal role remains unclear.
  • The influence of estrogen fading on systemic aging and cognitive function requires further investigation.

Purpose of the Study:

  • To investigate the causal link between estrogen receptor depletion and the aging of the hypothalamus-uterus-kidney (HUK) axis.
  • To elucidate the molecular mechanisms underlying estrogen depletion-induced renal and cognitive dysfunction.

Main Methods:

  • Utilized an ovariectomy (OVX)-induced estrogen receptor depletion rodent model.
  • Integrated multi-tissue (hypothalamus, uterus, kidney) data including proteomics, lipidomics, cytochemistry, and histopathology.
  • Assessed renal function and cognitive abilities using the Morris water maze test.

Main Results:

  • OVX rats exhibited altered prostaglandin D2 synthase (Ptgds) expression in the kidneys, uterus, and hypothalamus.
  • Degenerate renal function and impaired learning/memory were observed in OVX rats.
  • A regulatory axis involving estrogen receptors (ERβ), Ptgds, and HUK function was identified.

Conclusions:

  • Estrogen receptor depletion promotes HUK axis aging, primarily due to a renal ERβ/Ptgds signaling imbalance.
  • This imbalance contributes to the degenerate renal function and cognitive deficits observed in the model.
Keywords:
estrogen receptor betamenopauseprostaglandin D synthase 2‘hypothalamus-uterus-kidney’ axis

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