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Chorionic Gonadotropin ß-Subunit Gene Expression in the Marmoset Pituitary Is Controlled by Steroidogenic Factor 1, Early Growth Response Protein 1, and Pituitary Homeobox Factor 1

University Clinic Münster, Institute of Reproductive Medicine, D-48129 Münster, Germany

Address all correspondence and requests for reprints to: Prof. Dr. Jörg Gromoll, Institute of Reproductive Medicine, Domagkstrasse 11, D-48129 Münster, Germany. E-mail: joerg.gromoll{at}ukmuenster.de.

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 CGß 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 LßT2 cells showed that marmoset monkey CGß is GnRH responsive and activated similar to human LHß 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 CGß 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 CGß promoter activity was reduced after introduction of the human CGß 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.

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