title: Plasminogen deficiency attenuates postnatal erythropoiesis in male C57BL/6 mice through decreased activity of the LH-testosterone axis.
abstract: Novel roles for the serine protease plasmin have been implicated recently in physiological and pathological processes. However, whether plasmin is involved in erythropoiesis is not known. In the present study, we studied the consequences of plasminogen deficiency on erythropoiesis in plasminogen-deficient (Plg knockout [KO]) mice. Erythroid differentiation was attenuated in male Plg KO mice and resulted in erythroblastic accumulation within the spleen and bone marrow, with increased apoptosis in the former, erythrocytosis, and splenomegaly, whereas similar erythropoietic defect was less prominent in female Plg KO mice. In addition, erythrocyte lifespan was shorter in both male and female Plg KO mice. Erythropoietin levels were compensatory increased in both male and female Plg KO mice, and resulted in a higher frequency of burst-forming units-erythroid within the spleen and bone marrow. Surprisingly, we found that male Plg KO mice, but not their female counterparts, exhibited normochromic normocytic anemia. The observed sex-linked erythropoietic defect was attributed to decreased serum testosterone levels in Plg KO mice as a consequence of impaired secretion of the pituitary luteinizing hormone (LH) under steady-state condition. Surgical castration causing testosterone deficiency and stimulating LH release attenuated erythroid differentiation and induced anemia in wild-type animals, but did not further decrease the hematocrit levels in Plg KO mice. In addition, complementation of LH using human choriogonadotropin, which increases testosterone production, improved the erythropoietic defect and anemia in Plg KO mice. The present results identify a novel role for plasmin in the hormonal regulation of postnatal erythropoiesis by the LH-testosterone axis.
authors: Frontier Research Initiative, Institute of Medical Sciences, University of Tokyo, Tokyo, Japan.
authors: Yurai
authors: Y
authors: Okaji
authors: Yoshihiko
authors: Y
authors: Tashiro
authors: Ismael
authors: I
authors: Gritli
authors: Chiemi
authors: C
authors: Nishida
authors: Aki
authors: A
authors: Sato
authors: Yoko
authors: Y
authors: Ueno
authors: Sandra
authors: S
authors: Del Canto Gonzalez
authors: Makiko
authors: M
authors: Ohki-Koizumi
authors: Haruyo
authors: H
authors: Akiyama
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: Koichi
authors: K
authors: Hattori
authors: Beate
authors: B
authors: Heissig
mesh_terms: D000818:Animals; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005341:Fibrinolysin / Q000502:physiology; D007986:Luteinizing Hormone / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010958:Plasminogen / Q000172:deficiency / Q000502:physiology*; D013739:Testosterone / Q000502:physiology*
chemical_list: D004921:Erythropoietin; D013739:Testosterone; D010958:Plasminogen; D007986:Luteinizing Hormone; D005341:Fibrinolysin