Life and Medical Sciences
Cell & Developmental Biology
Wiley InterScience Backfile Collection 1832-2000
This immunoperoxidase study identifies the hepatocytes that synthesize alpha 2u globulin during male ontogeny and other endocrine states wherein its synthesis is modulated. To correlate biochemical parameters with the immunocytochemistry, alpha 2u globulin mRNA (alpha 2u mRNA) sequences were evaluated by Northern blot hybridization and Rot analysis to a cloned alpha 2u globulin cDNA probe and the functional level of this mRNA measured by cell-free translation. Alpha 2u globulin and its mRNA were detectable in the liver only after male rats reached puberty. During its developmental and hormonal induction, marked heterogeneity was observed; centrolobular hepatocytes showed the strongest staining, whereas periportal hepatocytes were devoid of, or weakly stained for, this protein. This difference between centrolobular and periportal hepatocytes was enhanced during development. Mature male rats exhibited the strongest staining reaction and the highest levels of hepatic alpha 2u globulin mRNA. Almost all hepatocytes in the adult male were stained; however, centrolobular ones were remarkably more stained than periportal ones. Female rat liver was devoid of this protein and of its mRNA. Following androgen administration to castrated female rats, or hydrocortisone administration to adrenalectomized male rats, the alpha 2u globulin mRNA level as well as the number and intensity of centrolobular alpha-2u-globulin-staining hepatocytes were increased in parallel. Following hypophysectomy, almost no alpha 2u globulin could be localized; likewise its mRNA was undetectable. However, when hypophysectomized adult male rats were treated with growth hormone, testosterone, thyroid hormone, and hydrocortisone, the hepatic immunocytochemical staining as well as the level of alpha 2u globulin mRNA sequences and of functional alpha 2u globulin mRNA, and the in vivo biosynthetic rate of alpha 2u globulin, became comparable to that of intact mature male rats. These studies indicate functional heterogeneity among hepatocytes which seems to be determined by their anatomical location within the hepatic lobule. Furthermore, hormonal and developmental induction of alpha 2u globulin involves both an increase in the number of hepatocytes committed to its synthesis and an increase in the rate of its synthesis in already committed cells. These events are accompanied by a concurrent increase in the hepatic alpha 2u globulin mRNA level.
Type of Medium: