Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.
The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.
Department of Animal Sciences (M.G., B.L.-S.) and The Interdepartmental Equipment Unit (E.Z.), The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; and Department of Marine Biotechnology (Y.Z.), University of Maryland Baltimore County and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202.
Matan
M
Golan
Department of Animal Sciences (M.G., B.L.-S.) and The Interdepartmental Equipment Unit (E.Z.), The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; and Department of Marine Biotechnology (Y.Z.), University of Maryland Baltimore County and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202.
Einat
E
Zelinger
Department of Animal Sciences (M.G., B.L.-S.) and The Interdepartmental Equipment Unit (E.Z.), The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; and Department of Marine Biotechnology (Y.Z.), University of Maryland Baltimore County and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202.
Yonathan
Y
Zohar
Department of Animal Sciences (M.G., B.L.-S.) and The Interdepartmental Equipment Unit (E.Z.), The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; and Department of Marine Biotechnology (Y.Z.), University of Maryland Baltimore County and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202.
Berta
B
Levavi-Sivan
D000818:Animals; D030801:Animals, Genetically Modified; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D052681:Gonadotrophs / Q000166:cytology* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000098:blood supply* / Q000166:cytology* / Q000378:metabolism; D015027:Zebrafish
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone