Plasticity in medaka gonadotropes via cell proliferation and phenotypic conversion

Abstract

Follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) produced by the gonadotropes, play a major role in control of reproduction. Contrary to mammals and birds, Lh and Fsh are mostly produced by two separate cell types in teleost. Here, we investigated gonadotrope plasticity, using transgenic lines of medaka (Oryzias latipes) where DsRed2 and hrGfpII are under the control of fshb and lhb promotors respectively. We found that Fsh cells first appear in the pituitary at 8 dpf. Similar to in Lh cells, Fsh cells show hyperplasia from juvenile to adult stages. Hyperplasia is stimulated by estradiol exposure. Both Fsh and Lh cells show hypertrophy during puberty with similar morphology. They also share similar behavior, using their cellular extensions to make networks. We observed bi-hormonal gonadotropes in juvenile and adult fish but not during larval stage where only mono-hormonal cells are observed, suggesting the existence of phenotypic conversion between Fsh and Lh in later stages. This is demonstrated in cell culture, where some Fsh start to produce lhb, a phenomenon enhanced by gonadotropin releasing hormone (Gnrh) stimulation. We have previously shown that medaka Fsh cells lack Gnrh receptors, but here we show that with time in culture, some Fsh cells start responding to Gnrh, while fshb mRNA levels are significantly reduced, both suggestive of phenotypic change. All together, these results reveal high plasticity of gonadotropes due to both estradiol sensitive proliferation and Gnrh promoted phenotypic conversion, and also shows that gonadotropes lose part of their identity when kept in cell culture.