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Updated: Feb 28, 2026

Gene Expression Analyses in Human Follicles
Published on: February 17, 2023
LHCGR Expression During Follicle Stimulating Hormone-Induced Follicle Growth Is Negatively Regulated by Eukaryotic
Thippeswamy Gulappa1, Bindu Menon1, K M J Menon1,2
1Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
Abstract:
We have shown that the transient changes in the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) messenger RNA (mRNA) during the ovarian cycle occurs, at least in part, through a posttranscriptional mechanism involving an LHCGR mRNA-binding protein (LRBP). Eukaryotic initiation factor 5A (eIF5A), an LRBP-interacting protein, participates in this process. eIF5A undergoes hypusination, a unique posttranslational modification that is necessary for its functions. This study examined the role of eIF5A in follicle-stimulating hormone (FSH)-induced LHCGR expression during follicular growth. Treatment of primary cultures of rat granulosa cells with FSH and 17β-estradiol (E2) showed a time-dependent increase in LHCGR mRNA expression. Conversely, inhibition of endogenous hypusination of eIF5A using N1-guanyl-1,7-diaminoheptane (GC7), a hypusination inhibitor, showed a greater increase in LHCGR mRNA expression over that produced by FSH and E2 alone. Further studies were carried out to determine the mechanism by which inhibition of hypusination of eIF5A causes an increase in LHCGR mRNA expression. Because LHCGR expression is negatively regulated by LRBP, the effect of inhibiting hypusination of eIF5A on LRBP expression was examined. The results showed a decrease in the expression of LRBP mRNA and protein when hypusination of eIF5A was inhibited by GC7. Because LRBP promotes LHCGR mRNA degradation, the results of this study support the notion that by inhibiting eIF5A hypusination, FSH reduces the expression of LRBP. This increases LHCGR mRNA expression by abrogating the inhibitory action of LRBP.
Insights
Follicle-stimulating hormone (FSH) regulates luteinizing hormone/choriogonadotropin receptor (LHCGR) expression by modulating eukaryotic initiation factor 5A (eIF5A) hypusination, impacting LHCGR mRNA levels.
Area of Science:
- Reproductive Endocrinology
- Molecular Biology
- Cellular Signaling
Background:
- Transient changes in luteinizing hormone/choriogonadotropin receptor (LHCGR) messenger RNA (mRNA) during the ovarian cycle are regulated by posttranscriptional mechanisms.
- An LHCGR mRNA-binding protein (LRBP) and its interacting protein, eukaryotic initiation factor 5A (eIF5A), are involved in this regulation.
- eIF5A requires a unique posttranslational modification called hypusination for its function.
Purpose of the Study:
- To investigate the role of eIF5A in follicle-stimulating hormone (FSH)-induced LHCGR expression during follicular growth.
- To elucidate the mechanism by which eIF5A hypusination influences LHCGR mRNA levels.
Main Methods:
- Primary cultures of rat granulosa cells were treated with FSH and 17β-estradiol (E2).
- The hypusination inhibitor N1-guanyl-1,7-diaminoheptane (GC7) was used to assess the impact of eIF5A hypusination inhibition.
- Expression levels of LHCGR mRNA, LRBP mRNA, and LRBP protein were quantified.
Main Results:
- FSH and E2 treatment increased LHCGR mRNA expression in a time-dependent manner.
- Inhibition of eIF5A hypusination with GC7 resulted in a greater increase in LHCGR mRNA expression compared to FSH and E2 alone.
- Inhibiting eIF5A hypusination led to decreased expression of LRBP mRNA and protein.
Conclusions:
- FSH signaling reduces LRBP expression by inhibiting eIF5A hypusination.
- Reduced LRBP levels abrogate its inhibitory effect on LHCGR mRNA, thereby increasing LHCGR expression.
- This study reveals a novel mechanism involving eIF5A hypusination in the regulation of LHCGR expression during follicular development.
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