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Updated: May 13, 2026
Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an Analysis of Human Pituitary Adenoma Tissue Proteome
Published on: April 2, 2018
Gonadotropin-releasing hormone receptor mRNA expression by human pituitary tumors in vitro
1Neuroendocrine Unit, Massachusetts General Hospital, Boston 02114.
Abstract:
An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin-releasing hormone (GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10(-8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude (a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors.
Insights
A third of human gonadotroph adenomas respond to gonadotropin-releasing hormone (GnRH). Researchers found that the presence of GnRH receptor (GnRH-Rc) mRNA predicts tumor responsiveness, suggesting biosynthetic defects cause nonresponsiveness.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Human gonadotroph adenomas exhibit varied responses to GnRH.
- Understanding the mechanisms behind these heterogeneous responses is crucial for pathogenesis and regulation.
Purpose of the Study:
- To investigate the role of GnRH receptor (GnRH-Rc) biosynthesis and cell-signaling pathways in gonadotropin responsiveness in human gonadotroph adenomas.
- To determine if GnRH-Rc expression correlates with GnRH responsiveness in these tumors.
Main Methods:
- Analyzed gonadotropin responsiveness to pulsatile GnRH in 13 human gonadotroph adenomas.
- Utilized reverse transcriptase/polymerase chain reaction (RTPCR) to detect follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis.
- Assessed GnRH receptor (GnRH-Rc) transcript presence using RTPCR.
Main Results:
- Four out of 13 tumors showed increased gonadotropin/subunit secretion in response to GnRH.
- GnRH antagonist Antide blocked GnRH-induced secretory increases in responsive tumors.
- GnRH-Rc transcripts were detected only in GnRH-responsive tumors and normal pituitary tissue, not in non-responsive adenomas.
Conclusions:
- Approximately one-third of human gonadotroph adenomas are responsive to GnRH in vitro.
- GnRH receptor mRNA detection in gonadotroph adenomas serves as a predictor of GnRH responsiveness.
- Defects in GnRH receptor biosynthesis may explain the lack of GnRH responsiveness in certain gonadotroph tumors.
