7 research outputs found
Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): Cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein
Searching for hormone-regulated genes in testicular Sertoli cells, we cloned and sequenced a cDNA of 3108 base pairs, named LRPR1 (signifying leucine-rich primary response gene 1). This cDNA sequence has an open reading frame of 2238 base pairs encoding a leucine-rich protein of 746 amino acid residues with a relative molecular mass of 85.6 kDa. As much as 16% of the amino acid residues is leucine. Database analysis revealed significant similarity of LRPR1 to the human brain cDNA sequence EST00443, but not to any other sequences present in databases. The expression of LRPR1 mRNA in Sertoli cells is strongly and rapidly up-regulated by follicle-stimulating hormone (FSH). The level of LRPR1 mRNA was very low in Sertoli cells isolated from 21-day-old rats and cultured for 3 days in the absence of FSH, but LRPR1 mRNA expression was markedly increased within 2 h after addition of FSH to these cultures. A maximal response was reached within 4 h. Dibutyryl-cyclic AMP [(Bu)2cAMP] and forskolin had similar effects compared to FSH, indicating that cAMP acts as a second messenger in the regulation of LRPR1 expression. The up-regulation of LRPR1 mRNA expression by FSH was also observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that FSH regulates LRPR1 mRNA expression through a direct mechanism which does not require de novo protein synthesis. Thus, LRPR1 represents a primary response gene in FSH action on Sertoli cells. The presently available data indicate that LRPR1 mRNA expression is regulated specifically by FSH, since several other hormones and growth factors did not affect LRPR1 mRNA expression in the cultured Sertoli cells. LRPR1 mRNA expression is relatively high in testis, ovary and spleen. A much lower mRNA level was found in brain and lung, and no expression was detected in liver, kidney, heart, muscle, pituitary gland, prostate, epididymis and seminal vesicle. The basal level of testicular LRPR1 expression in intact 21-day-old rats was markedly increased within several hours after a single i.p. injection of FSH, indicating that in vivo LRPR1 mRNA expression may appear to be a useful parameter to evaluate testicular FSH action
Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development
The fragile X syndrome is the most frequent hereditary form of mental
retardation. This X-linked disorder is, in most cases, caused by an
unstable and expanding trinucleotide CGG repeat located in the
5'-untranslated region of the gene involved, the fragile X mental
retardation 1 (FMR1) gene. Expansion of the CGG repeat to a length of more
than 200 trinucleotides results in silencing of the FMR1 gene promoter
and, thus, in an inactive gene. The clinical features of male fragile X
patients include mental retardat
Differential regulation of leucine-rich primary response gene 1 (LRPR1) mRNA expression in rat testis and ovary
In immature rat Sertoli cells, leucine-rich primary response gene 1
(LRPR1) represents a follicle stimulating hormone (FSH)-responsive gene;
the function of the encoded protein is not yet known. LRPR1 mRNA
expression is up-regulated very rapidly and specifically by FSH, both in
cultured Sertoli cells and in vivo in regulation in more detail, in testis
and ovary of fetal, immature, and adult rats. In addition, we have studied
the expression of FSH receptor (FSHR) mRNA in relation to LRPR1 mRNA
expression. In rat testis, LRPR1 mRNA and FSHR mRNA followed a similar
expression pattern, during postnatal development and also at different
stages of the spermatogenic cycle in the adult rat. Furthermore, after
short-term challenge of the FSH signal transduction pathway in intact
immature rats by injection with a relatively high dose of FSH, an inverse
relationship between LRPR1 mRNA (up-regulation) and FSHR mRNA expression
(down-regulation) was observed. Similar studies in the ovary provided
completely different results. LRPR1 mRNA in the postnatal ovary is present
well before expression of FSHR mRNA can be first detected. In addition,
incubation of ovaries of immature rats with FSH or dibutyryl cyclic AMP
(dbcAMP) did not result in up-regulation of LRPR1 mRNA expression. During
fetal development, the LRPR1 mRNA expression pattern involved many more
tissues, in contrast to the relatively tissue-specific expression of LRPR1
mRNA in gonads of 21 day old and adult rats. Moreover, LRPR1 mRNA
expression could be detected as early as 12.5 days post-coitum, whereas
FSHR mRNA is absent at this stage of fetal development. We concluded that
the pronounced regulation of LRPR1 by FSH observed in the immature rat
testis does not occur in the ovary. Furthermore, in the ovary LRPR1 mRNA
expression does not appear to be dependent on FSH action. Finally, the
LRPR1 gene product may play a general role during fetal development