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Glucocorticoid receptor expression and glucocorticoidtherapeutic effect in nasal polyps

Peng Li MDYuan Li MBYong-Qi Li MDQin-Tai Yang MDGe-Hua Zhang MD

Department of Otolaryngology Head and Neck Sur-gery, The Third Affiliated Hospital, Sun Yat-SenUniversity, Guangzhou, Guangdong, 510630 China

Manuscript submitted 21st January, 2010 Manuscript accepted 23rd March, 2010 Clin Invest Med 2010; 33 (3): E181-E188.

Abstract

Purpose: To investigate the expression and quantity of glucocorticoid receptor- and - in polyp tissues takenfrom the patients treated were subsequently treated withtopical glucocorticoid (GC).Methods: Eighty patients with nasal polyps were initiallyenrolled in the study. All polyp specimens were obtained

prior to treatment. Patients then received daily topical GCspray treatment for one month. Polyp specimens were

tested for glucocorticoid receptor (GR) GR- and GR- mRNA expression using fluorescent quantitative-reversetranscription-polymerase chain reaction (FQ-RT-PCR).Thirty healthy nasal mucosa tissue samples were tested atthe same time.Results: Forty patients finished the study and were dividedinto two groups: GC-sensitive (n=26) and GC-insensitive(n=14), according to treatment results. GR- mRNAexpression in the nasal polyp tissues of the GC-insensitivegroup (5.720.58 102 copies/g) was higher than that inthe GC-sensitive group (4.820.28 102 copies/g, P


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Eighty patients (56 males and 24 females) withnasal polyps, identified by anterior rhinoscopy or na-sal endoscopy in the out-patient department of our hospital, were enrolled in the study. Patients had nohistory of allergic rhinitis, asthma, aspirin sensitivity,

previous surgery for chronic sinusitis or pregnancy.The average age was 42 years old. Nasal polyp speci-mens were obtained via nasal endoscopy. Before tis-sue sampling, all patients avoided GC systemic ad-ministration (for at least two months) or GC local ad-ministration (for at least one month).

The normal nasal mucosa was obtained from theinferior turbinate mucosa from 30 patients with de-flection of nasal septum (without history of allergic

rhinitis) who underwent surgical treatment in our hospital. The controls included 22 males and 8 fe-males, with an average age of 31 years old. None of them had a history of nasal or sinus disease, allergicrhinitis or upper respiratory tract infection, and nonehad GC treatment for at least 4 weeks prior to surgery.

All specimens were stored immediately at -80Cfor future use. Fluticasone propionate (200 g/d) wasadministrated once a day. One month after the GC lo-cal treatment, the therapeutic efficiency of GC was

evaluated as descrbribed by Jankowski et al. 6 Of the 80 patients originally identified, 40 (27

males and 13 females, mean age 39.2 years) werescreened for GC efficacy at the end of the study.Twenty-six cases had a score >3 - the most sensitivegroup for GC therapy, and 14 cases had a score


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Li et al. Glucocorticoids and nasal polyps

2010 CIM Clin Invest Med Vol 33, no 3, June 2010 E184 .

A

B

FIGURE 1. Expression of GR- mRNA. (A) Gradient amplification curves for GR- fluorescence quantification, (B) Standardcurve for GR- fluorescence quantification


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vealed the ability of GR- to act as a strong negativeinhibitor of GR- activity through a mechanism thatinvolves the formation of transcriptionally impairedGR- -GR- heterodimers. 7,8

In our study, the GR- mRNA expression wasfound to be higher for the GC-insensitive group incomparison with the GC-sensitive group (P


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method for quantitative analysis: there is a direct rela-tionship between the intensity of the fluorescence sig-nal and the amplification products at each time point,and the initial product can therefore be quantified di-rectly. Because its sensitivity range is 0-10 copies/ml,fluorescence quantitative PCR can reflect the productamount of the target gene in tissue more scientificallythan the conventional PCR. In Pujolss study, the

patients with nasal polyps were divided into GC-treated and untreated groups. 16 Even though therewere steroid-insensitive individuals in the GC-treatedgroup, because of the relatively small number, quanti-tative values of GR and GR expression from such

patients were likely masked by GR and GR

expression level in the majority of GC-sensitive patients. It may therefore be difficult to extrapolatefrom that data the actual quantitative levels of expression of the GR and GR in the steroid-insensitive patients. This may help explain why resultsappeared to differ in that study.

Based on the increased expression of GR- has been reported in patients with glucocorticoid-insensitive asthma and other diseases. 3-5 Therefore,according to the results of our study, the level of GR-

mRNA expression and the ratio of GR- to GR- mayreflect the effect of GR- on GR- activity within thenasal cavity. If overexpression of GR- mRNA ac-companied lower ratio of GR- to GR- was found innasal polyps, the result may show the condition of glucocorticoids insensitivity in the patients nasal cav-ity, which might result in poor effectiveness of localGC treatment. Otherwise, if the nasal polyps have theexpression of GR- mRNA and the ratio of GR- toGR- in normal level, local GC treatment for the pa-

tient might be effective because of glucocorticoid-sensitive condition in nasal polyps. So, before thetherapy of local GC treatment for the patients withnasal polyps, testing their level of GR- / expressionin nasal cavities might be significant for evaluation of glucocorticoid therapeutic effect in patients with nasal

polyps.

Currently, local GC treatment is still one of theeffective methods for nasal polyps. Therefore, it isnecessary to explore the mechanism of GC insensitiv-ity for nasal polyps, which will supply a basis for newtreatment strategy for the nasal polyps that is refrac-tory to GC treatment.

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Correspondence to:

Dr. Peng LiDepartment of Otolaryngology Head and Neck Surgery,The Third Affiliated Hospital, Sun Yat-Sen University,

Guangzhou, Guangdong,510630 China.E-mail: [email protected]




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