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. 2022 Apr 21;27(9):2671.
doi: 10.3390/molecules27092671.

Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches

Zsuzsanna Szabo  1 , Eva Juhasz  2 , Andrew V Schally  3   4   5 , Balazs Dezso  6 , Sandor Huga  7 , Zoltan Hernadi  7 , Gabor Halmos  1   3 , Csongor Kiss  2
Affiliations

Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches

Zsuzsanna Szabo et al. Molecules. .

Abstract

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.

Keywords: GHRH; human endometrial carcinoma; receptors for GHRH; splice variants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative RT-PCR analysis of the splice variants of GHRH receptor in a human pituitary sample used as a positive control for PCR (lanes 1–4) and in an endometrium carcinoma sample from patient 29 (lanes 7–10). Lane 5, 50-bp DNA Step Ladder. PCR products were of the expected sizes: SV1 415-bp, SV2 523-bp, SV3 245-bp (present only in the pituitary) and SV4 120-bp long. PCR products were separated by agarose gel electrophoresis and stained with ethidium bromide. Lane 6: negative template control.
Figure 2
Figure 2
Representative RT-PCR analysis of the expression of mRNA for GHRH ligand. Lanes 1–11: representative endometrium tumor tissues; lane 12: positive control (human pituitary); lane 13: no template control; lane 14: 50-bp DNA ladder. PCR products were of the expected size of 150 base pairs. In samples with low or no expression, a primer dimer was also detected.
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