Alternative splicing of follicle-stimulating hormone receptor pre-mRNA: cloning and characterization of two alternatively spliced mRNA transcripts

Glycoprotein hormone receptors contain a large extracellular domain that is encoded by multiple exons, facilitating the possibility of expressing alternatively spliced transcripts. We have cloned two new splice variants of the rat follicle-stimulating hormone (FSH) receptor gene: FSH-R1 and FSH-R2. The splice variant FSH-R1 differs from the full-length FSH receptor mRNA by the inclusion of a small extra exon between exons 9 and 10. FSH-R2 lacks the first three base pairs o

Transient down-regulation of androgen receptor messenger ribonucleic acid (mRNA) expression in Sertoli cells by follicle-stimulating hormone is followed by up-regulation of androgen receptor mRNA and protein

In Sertoli cells from 21-day-old rats, the expression of the mRNA encoding the alpha-subunit of inhibin, and the production of immunoreactive inhibin are stimulated by follicle-stimulating hormone (FSH). In contrast, the amount of beta B-subunit mRNA is not increased after FSH treatment of the cells, and the ratio between bioactive and immunoactive inhibin decreases after stimulation with FSH. These data suggest that the beta B-subunit is the limiting factor in the production of bioactive inhibin. The aim of the present experiments was to investigate the effect of changes in the amount of beta B-subunit mRNA on the production of bioactive and immunoreactive inhibin. During early postnatal testicular development, the relative amounts of the 4.2 kb and 3.5 kb mRNAs encoding the beta B-subunit of inhibin changed markedly. The meaning of this changing ratio between beta B-subunit mRNAs is not clear, since both mRNAs are actively translated, as demonstrated by polysomal analysis. The total amount of beta B-subunit mRNA correlated with the in vitro production of bioactive inhibin as published earlier. Prolonged stimulation of cultured Sertoli cells from 14-day-old rats with 4 beta-phorbol 12-myristate 13-acetate (PMA) caused a decreased expression of the beta B-subunit mRNAs, presumably by down-regulation of protein kinase C. A similar effect was obtained after addition of the calcium ionophore A23187. Concomitantly, a decreased production of bioactive inhibin was observed. Furthermore, Western blotting revealed that secr

Follitropin receptor down-regulation involves a cAMP-dependent post-transcriptional decrease of receptor mRNA expression

The androgen receptor (AR) is activated upon binding of testosterone or dihydrotestosterone and exerts regulatory effects on gene expression in androgen target cells. To study transcriptional regulation of the rat AR gene itself, the 5' genomic region of this gene was cloned from a genomic library and the promoter was identified. S1-nuclease protection analysis showed two major transcription start sites, located between 1010 and 1023 bp upstream from the translation initiation codon. The area surrounding these start sites was cloned in both orientations in a CAT reporter plasmid. Upon transfection of the constructs into COS cells, part of the promoter stimulated transcription in an orientation-independent manner, but the full promoter showed a higher and unidirectional activity. In the promoter/reporter gene constructs, transcription initiated from the same positions as in the native gene

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

Is cognitive functioning associated with subjective quality of life in young adults with spina bifida and hydrocephalus?

Objective: To test the hypothesis that cognitive functioning is associated with subjective quality of life of young adults with spina bifida and hydrocephalus (SBHC). Design: Cross-sectional multi-centre study in The Netherlands. Subjects: A total of 110 young adults with SBHC (16-25 years old, 63% female). Methods: Cognitive domains measured were intelligence (Raven Standard Progressive Matrices), memory (Wechsler Memory Scale) and executive functioning (Wisconsin modified Card Sorting Test (WmCST), Trail Making Test A and B (TMT) and UNKA word production test). Subjective quality of life was measured with a visual analogue scale. Correlations and hierarchical regression analysis controlling for age, gender and functional independence were applied. Results: The TMT score was significantly associated (-0.25) with subjective quality of life. In the hierarchical regression analysis both the WmCST and TMT scores were significant determinants of subjective quality of life (Beta values 0.24 and -0.31 respectively). Intelligence, memory and word production were not related to subjective quality of life. All 5 cognitive variables together explained a significant additional 14.6%, of the variance of subjective quality of life (total explained variance 19.9%). Conclusion: Executive functioning was associated with subjective quality of life in young adults with spina bifida and hydrocephalus. This finding underlines the importance of examining cognitive functioning of persons with SBHC in addition to medical and functional status in medical care and outcome research