Female Hormone hCG Seen to Protect Key Neurons in Mouse Study
The female hormone known as chorionic gonadotropin (hCG) protects nerve cells in the brain that are lost in people with Parkinson’s disease, a mouse model study showed, reportedly for the first time.
These findings suggest that hCG may be an effective therapeutic agent to slow Parkinson’s progression, its researchers concluded.
The study, “Effects of hCG on DA neuronal death of Parkinson’s disease,” was published in the journal Biochemical and Biophysical Research Communications.
Across all age groups, Parkinson’s disease occurs twice as often in men than it does in women. As such, sex differences may provide clues to finding treatment targets to stop or slow disease progression.
The protein hormones — luteinizing hormone (LH) and chorionic gonadotropin (hCG) — play an essential role in the female reproductive system and are found at higher levels in women than in men. Because of their similarities, both LH and hCG bind to the same LHCGR receptor.
hCG is known to mediate the activation of pathways that regulate the survival of dopaminergic neurons — the dopamine-producing nerve cells that help to control movement and are lost in Parkinson’s. Clinically, the hormone also works to partly ease behavioral disorders in people with the condition.
However, the impact of hCG on the survival of dopaminergic neurons in Parkinson’s has yet to be explored.
Researchers at the Guangdong Pharmaceutical University in China investigated the potential neuroprotective effects of hCG in a mouse model of Parkinson’s disease induced by MPTP, a neurotoxin that destroys dopaminergic neurons.
They first measured changes in LH and its LHCGR receptor. In response to MPTP induction, blood levels of LH fell significantly. At the same time, there was a drop in the activity of the gene that encodes for LH in the substantia nigra, the region of the brain where dopaminergic neurons are lost.
Although LHCGR protein levels did not change significantly with the neurotoxin’s use, the activity of the receptor in the substantia nigra decreased. This activity was restored following hCG treatment.
Next, in MPTP-exposed mice, suppressing (knocking down) LHCGR production increased the loss of dopaminergic neurons, from 56.22 to 74.15%, compared with MPTP exposure alone. This indicated that “knocking down the LHCGR aggravates MPTP-induced [dopaminergic] neuronal death,” the researchers wrote.
“These results indicate that LHCGR activity is quite important for the death of [dopaminergic] neurons, and enhancing LHCGR activity by hCG is a potential strategy for treatment of [Parkinson’s disease],” they added.
Compared to a saline-treated control mouse group, the number of dopaminergic neurons in the substantia nigra of mice after MPTP exposure fell by 59.63%. After hCG treatment, the number of dopaminergic neurons in this MPTP group was 32.29% lower, a statistically significant improvement.
Consistently, the density of neurons decreased from 43.64% after MPTP to 21% with hCG, “indicating that hCG protects dopaminergic neurons” and presents “a new idea for the treatment and clinical medication of [Parkinson’s disease],” the investigators wrote.
Lastly, in both cells and the animal model, experiments showed that hCG exerted its neuroprotective effects by blocking the activity of GSK3-beta, an enzyme that mediates the death of dopaminergic neurons in Parkinson’s. The “specific mechanism of hCG’s regulating of [GSK3-beta] should be further explored,” the investigators noted.
“Our results show, for the first time, that hCG restores the decrease of LHCGR activity and protects [dopaminergic] neuronal death in the MPTP model, and the inhibition of [GSK3-beta] activation is involved in this protective effect,” they concluded. “Therefore, hCG could be considered as an effective therapeutic agent to hinder [Parkinson’s disease] progression.”
Further study, however, is warranted “to explore if there are other underlying molecular mechanisms involved,” the scientists added.
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