3973

LHCGR

HHG|LCGR|LGR2|LH/CG-R|LH/CGR|LHR|LHRHR|LSH-R|ULG5;luteinizing hormone/choriogonadotropin receptor;LHCGR;luteinizing hormone/choriogonadotropin receptor

hypergonadotropic hypogonadism|lutropin-choriogonadotropic hormone receptor|lutropin/choriogonadotropin receptor

2p21

protein-coding

BACKGROUND: Malignant neoplasia of the adrenal cortex is usually associated withvery poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence ordissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goalof the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizinghormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. METHODS: We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. RESULTS: Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, wasdetected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed onthose tumors with better clinical outcome. CONCLUSION: Our data suggest that theexpression of GATA-6 in human adrenal cortex is not affected by tumorigenesis. GATA-4 expression is more abundant in MR tumors, while NM tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors.

While a germline activating mutation of the luteinizing hormone receptor (LHR) gene is known to cause autonomous production of testosterone from testicular Leydig cells in male-limited precocious puberty, only a few studies have addressed the role of somatic LHR mutation in testicular pathology. The authors report a case of a 6-year-old boy who developed secondary sex characteristics including facial acne, enlarging genitalia, and aggressive behavior, for which serial biochemical evaluation confirmed the status of peripheral precocious puberty. Examination revealed asymmetrical testicular volume, following which a left testicular tumor was detected through ultrasonography. A left orchiectomy was performed, and histopathology revealed a well-circumscribed Leydig cell tumor Molecular study of the exon 11 of the LHR gene revealed a missense mutation at the nucleotide position 1,732, leading to a substitution of histidine for aspartic acid at codon 578. Interestingly, the substitution was consistent with ALL previously reported LHR alteration in pediatric Leydig cell adenoma, but which had never before been reported in male-limited precocious puberty, suggesting that the mutation is a molecular signature of the adenoma.