Differential regulation of the luteinizing hormone genes in teleosts and tetrapods due to their distinct genomic environments – Insights into gonadotropin beta subunit evolution

The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are essential for the control of vertebrate reproduction. Although the molecular structures of these two hormones are well conserved from teleosts to mammals, some studies report differences in their regulatory mechanisms of gene expression between teleosts and tetrapods. In the present study, we examined the molecular evolution of the gonadotropin gene loci in vertebrates and found that there is a syntenic conservation among the teleost fshb and tetrapod fshb and lhb loci. However, the teleost lhb locus has no syntenic homology to either tetrapod lhb or teleost fshb; this fact suggests that an extensive genome-wide rearrangement of the lhb locus, caused by an accelerated genome evolution speed after the third round of genome-wide duplication, occurred in the teleost lineage. We subsequently demonstrated by double labeling in situ hybridization using a teleost medaka that the fshb and lhb genes in teleosts are expressed in completely separate cellular populations in the pituitary, which is different in tetrapods. Furthermore, the expression analysis in ovariectomized and steroid-treated medaka revealed that, under breeding conditions, the expression of the medaka LHβ was down-regulated by ovariectomy and recovered by treatment with gonadal steroids; this result is also completely opposite in mammals, where the steroids have negative-feedback effects on LHβ expression. We suggest that these differences between teleosts and mammals in the cellular expression pattern and dynamic expressional changes of the lhb gene are the result of the drastic changes in the genomic environment of the lhb gene that occurred early in teleost evolution.

► Synteny is conserved among teleost fshb, tetrapod fshb and lhb loci.
► Teleost lhb lacks synteny with neither teleost fshb nor tetrapod fshb/lhb.
► Teleost lhb cells do not co-express fshb unlike tetrapod gonadotrophs.
► Lhb expression is upregulated in teleosts that is opposite to tetrapod cases.
► We hypothesize drastic genomic rearrangement changed teleost lhb properties.