Functional and developmental heterogeneity of pituitary lactotropes in medaka

In fish, prolactin-producing cells (lactotropes) are located in the anterior part of the pituitary and play an essential role in osmoregulation. However, small satellite lactotrope clusters have been described in other parts of the pituitary in several species. The functional and developmental backgrounds of these satellite clusters are not known. We recently discovered two distinct prolactin-expressing cell types in Japanese medaka (Oryzias latipes), a euryhaline species, using single cell transcriptomics. In the present study, we characterize these two transcriptomically distinct lactotrope cell types and explore the hypothesis that they represent spatially distinct cell clusters, as found in other species. Single cell RNA sequencing shows that one of the two lactotrope cell types exhibits an expression profile similar to that of stem cell-like folliculo-stellate cell populations. Using in situ hybridization, we show that the medaka pituitary often develops additional small satellite lactotrope cell clusters, like in other teleost species. These satellite clusters arise early during development and grow in cell number throughout life regardless of the animal's sex. Surprisingly, our data do not show a correspondence between the stem cell-like lactotropes and these satellite lactotrope clusters. Instead, our data support a scenario in which the stem cell-like lactotropes are an intrinsic stage in the development of every spatially distinct lactotrope cluster. In addition, lactotrope activity in both spatially distinct lactotrope clusters decreases when environmental salinity increases, supporting their role in osmoregulation. However, this decrease appears weaker in the satellite lactotrope cell clusters, suggesting that these lactotropes are regulated differently.