Characterization of GPR101 transcript structure and expression patterns.
We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X-LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes. GPR101 was the only gene highly expressed in their pituitary lesions, but little is known about its expression patterns. In this work, GPR101 transcripts were characterized in human tissues by 5'-Rapid Amplification of cDNA Ends (RACE) and RNAseq, while the putative promoter was bioinformatically predicted. We investigated GPR101 mRNA and protein expression by RT-quantitative PCR (qPCR), whole-mount in situ hybridization, and immunostaining, in human, rhesus monkey, rat and zebrafish. We identified four GPR101 isoforms characterized by different 5'-untranslated regions (UTRs) and a common 6.1kb long 3'UTR. GPR101 expression was very low or absent in almost all adult human tissues examined, except for specific brain regions. Strong GPR101 staining was observed in human fetal pituitary and during adolescence, whereas very weak/absent expression was detected during childhood and adult life. In contrast to humans, adult monkey and rat pituitaries expressed GPR101, but in different cell types. Gpr101 is expressed in the brain and pituitary during rat and zebrafish development; in rat pituitary, Gpr101 is expressed only after birth and shows sexual dimorphism. This study shows that different GPR101 transcripts exist and that the brain is the major site of GPR101 expression across different species, although divergent species- and temporal-specific expression patterns are evident. These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species.
Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Giampaolo
G
Trivellin
Section on Cellular SignalingEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Ivana
I
Bjelobaba
Department of EndocrinologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Adrian F
AF
Daly
Department of Obstetrics and GynecologyUniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Darwin O
DO
Larco
Department of EndocrinologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Leonor
L
Palmeira
Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Fabio R
FR
Faucz
Department of PathologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Albert
A
Thiry
Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA Department of PediatricsUniversity of Sao Paulo, Ribeirao Preto, São Paulo, Brazil.
Letícia F
LF
Leal
Department of EndocrinologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Liliya
L
Rostomyan
Laboratory of PathologyNational Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Martha
M
Quezado
Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Marie Helene
MH
Schernthaner-Reiter
Section on Cellular SignalingEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Marija M
MM
Janjic
Department of EndocrinologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium Hopital FochService d'Anatomie et Cytologie Pathologiques, Suresnes Cedex, France.
Chiara
C
Villa
Department of Obstetrics and GynecologyUniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
T John
TJ
Wu
Section on Cellular SignalingEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Stanko S
SS
Stojilkovic
Department of EndocrinologyUniversity of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Albert
A
Beckers
Division of Developmental BiologyEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Benjamin
B
Feldman
Section on Endocrinology and GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA stratakc@mail.nih.gov.
Constantine A
CA
Stratakis
D000328:Adult; D000818:Animals; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D020506:Untranslated Regions; D015027:Zebrafish
C112345:PRLHR protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D020506:Untranslated Regions
GPR101; expression analysis; hypothalamus; pituitary; transcripts structure