Chorionic gonadotropin beta-subunit gene expression in the marmoset pituitary is controlled by steroidogenic factor 1, early growth response protein 1, and pituitary homeobox factor 1.
In most mammals, the gonads are under the control of the pituitary gonadotropins LH and FSH. However, in the common marmoset monkey Callithrix jacchus, no LH is detectable in the pituitary but chorionic gonadotropin (CG) instead, normally produced in the placenta. This study investigated the mechanism of CGbeta subunit activation in the pituitary and why humans do not express CG in the pituitary. 5'-Rapid amplification of cDNA ends, EMSA, and promoter-driven luciferase assays performed with the gonadotropic LbetaT2 cells showed that marmoset monkey CGbeta is GnRH responsive and activated similar to human LHbeta by the transcription factors steroidogenic factor 1 (SF1), early growth response protein 1 (Egr1), and pituitary homeobox factor 1 (Pitx1) and displayed a transcriptional start site 7 bp upstream of exon 1. In contrast, the human CGbeta promoter displayed in the binding elements for pituitary homeobox factor 1 and early growth response protein 1 three consensus sequence mismatches, leading to very low activity that could be drastically increased by mutation to the consensus sequences. Vice versa, marmoset CGbeta promoter activity was reduced after introduction of the human CGbeta mismatches. An in vivo study in pregnant marmoset monkeys showed that during pregnancy, there is no significant decrease of pituitary CG production, contrasting human LH down-regulation. In conclusion, pituitary CG production is lacking in humans due to the absence of appropriate DNA-binding elements, which are present in marmosets, thereby enabling GnRH activation of expression. However, during pregnancy of marmosets, pituitary CG expression is not inhibited.
Henke
Alexander
A
Institute of Reproductive Medicine, University Clinic Münster, Domagkstrasse 11, Münster, Germany.
Luetjens
C Marc
CM
Simoni
Manuela
M
Gromoll
Jörg
J
D000818:Animals; D001483:Base Sequence; D002144:Callithrix; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000097:blood / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D006063:Chorionic Gonadotropin; D051766:Early Growth Response Protein 1; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D054339:Steroidogenic Factor 1; C101485:homeobox protein PITX1; D007986:Luteinizing Hormone; D008156:Luciferases