Age- and sex-specific promoter function of a 2-kilobase 5 '-flanking sequence of the murine luteinizing hormone receptor gene in transgenic mice

A transgenic (TG) mouse model carrying a 2-kb murine LH receptor (LHR) prom oter/beta-galactosidase (beta-GAL) fusion gene was created to study the reg ulatory function of the 5'-flanking region of the murine LHR gene. Of the f ive TG mouse Lines produced, three displayed high beta-GAL expression in th e testis, but none showed any expression in the ovary. In addition, all mou se lines of both sexes expressed beta-GAL consistently in the brain, most p rominently in hippocampus, hypothalamus, midbrain, and cortex. Weak stainin g was found in a few pituitary samples. All other tissues examined were neg ative for transgene expression. In support of sex-specific gonadal expressi on of the transgene, transient transfection of the LHR/beta-GAL gene constr uct into immortalized mouse granulosa (KK-1) and Leydig (mLTC-1) tumor cell s revealed a more than 5-fold higher expression level in the Leydig cells. Histological examination of the TG testes demonstrated strong beta-GAL expr ession in Leydig cells, but, unexpectedly, also in elongating spermatids of adult age and in some spermatogonia of the neonatal testis. The functional significance of the latter findings remains open. The transgene was only e xpressed in adult Leydig cells; no expression was found in the fetal popula tion of these cells. Hence, these findings indicate that the immediate 2-kb fragment of the murine LHR 5'-flanking sequence is transcriptionally activ e only in adult Leydig cells and certain brain areas, but of her promoter s equences are apparently needed for ovarian and fetal testicular expression of the LHR gene.