Comprehensive histological and immunological studies reveal a novel glycoprotein hormone and thyrostimulin expressing proto-glycotrope in the sea lamprey pituitary

In the adenohypophysis (anterior pituitary) of all gnathostomes, there are six tropic cell types: corticotropes, melanotropes, somatotropes, lactotropes, gonadotropes and thyrotropes; each cell type produces specific tropic hormones. In contrast, we report in this study that there are only four tropic cell types in the sea lamprey ( Petromyzon marinus ) adenohypophysis. We specifically focused on the cell types that produce the glycoprotein hormones (GpHs). The gnathostome adenohypophyseal GpHs are follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and thyrostimulin. However, lampreys only have two heterodimeric adenohypophyseal GpHs consisting of unique α and β subunits, lamprey GpH (lGpH) (lGpA2/lGpHβ) and thyrostimulin (lGpA2/lGpB5). We used an array of histological techniques to determine the (co)-localization and (co)-expression of the lGpH and thyrostimulin subunits in the lamprey adenohypophysis at different life stages (larval, parasitic, adult) and to identify their synthesizing cell(s). The thyrostimulin subunits (lGpA2/lGpB5) were co-expressed throughout the adenohypophysis (larval, parasitic, and adult), while the GpH β-subunit (lGpHβ) exhibited localized distribution (adult); all three subunits were co-localized and co-expressed, suggesting that both GpHs are synthesized in the same cells, novel proto-glycotropes, in specific adenohypophyseal regions at different life stages. In summary, we provide the first comprehensive study using histology, transmission electron microscopy, in situ hybridization and immunohistochemistry that strongly supports further evidence for four definitive adenohypophyseal cell types in the lamprey, including: corticotropes, somatotropes, melanotropes, and the first identification of a novel proto-glycotrope. In addition, our studies show that there is developmental and region-specific co-localization and co-expression of lGpH and thyrostimulin in the lamprey adenohypophysis.