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.

Endocrinology
|June 13, 2017
PubMed

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.

Related Concept Videos

Folliculogenesis01:20

Folliculogenesis

Folliculogenesis is the development of ovarian follicles, the specialized structures within the ovarian cortex where oogenesis, or egg development, occurs. This process is essential for female reproductive health and begins during fetal development when primordial follicles are formed. Each primordial follicle comprises a primary oocyte in the center, surrounded by a single layer of squamous pre-granulosa cells. These follicles remain dormant in late prophase I of meiosis until triggered by...
2.9K
Hormonal Regulation of the Menstrual Cycle01:22

Hormonal Regulation of the Menstrual Cycle

The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
1.9K
Hormonal Control of the Ovarian Cycle01:30

Hormonal Control of the Ovarian Cycle

The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle.  At puberty, GnRH secretion increases in both frequency and...
7.2K
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
4.0K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.5K
Multipotency and Niche of Bulge Stem Cell01:06

Multipotency and Niche of Bulge Stem Cell

A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
4.3K