Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition.

Bowen RL, Verdile G, Liu T, Parlow AF, Perry G, Smith MA, Martins RN, Atwood CS

The Journal of biological chemistry9 Feb 2004Cited by 127 (Europe PMC)

PMID14871891DOI10.1074/jbc.m311993200PepBankPUB-14871891

Publisher page PubMedAsk about this study

Summary

Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-beta (Abeta) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-beta precursor protein (AbetaPP) expression but did alter AbetaPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Abeta, decreased alphaAbetaPP secretion, and increased AbetaPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Abeta secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In C57Bl/6J mice, leuprolide reduced total brain Abeta1-42 concentrations 3.5-fold after 8 weeks.
In plain wordsIn mice, leuprolide reduced brain Abeta1-42 concentrations 3.5-fold after 8 weeks.
Peptide
Leuprolide
Outcome
DecreaseTotal brain Abeta1-42
Study
mousen: not reported in source
C57Bl/6J mice
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Measurements
Abeta1-42 reduction
3.5 fold
after 8 weeks
P value upper bound
0.0001
Abeta1-42 reduction
Source sentences
Summary
Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins.
Show in the study text Report a problemFND-1487189101
02AnimalAnimal study (in vivo)Efficacy outcome
In C57Bl/6J mice, leuprolide reduced total brain Abeta1-40 concentrations 1.5-fold after 8 weeks.
In plain wordsIn mice, leuprolide reduced brain Abeta1-40 concentrations 1.5-fold after 8 weeks.
Peptide
Leuprolide
Outcome
DecreaseTotal brain Abeta1-40
Study
mousen: not reported in source
C57Bl/6J mice
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · 8 weeksAs given in this study (mouse).
Measurements
Abeta1-40 reduction
1.5 fold
after 8 weeks
P value upper bound
0.024
Abeta1-40 reduction
Source sentences
Summary
Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins.
Show in the study text Report a problemFND-1487189102

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3NCT00231946

ALADDIN Study - Phase III: Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (VP-AD-301)

Voyager Pharmaceutical Corporationn = 555Start Sept 2005

Alzheimer's Disease

Trial page ClinicalTrials.govUpdated 20 Sept 2007

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:37 UTC
First added · source update from Europe PMC

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