Recently, we have localized a rat urinary and serum protein Alpha 2u globulin (Alpha2u) in the anterior pituitary and shown the absence of specific Alpha2u mRNA sequences in pituitary RNA extract. Pituitary intermediate and posterior lobes were devoid of Alpha2u globulin. Intravenously injected Alpha2u was specifically taken up by anterior pituitary cells and by no other tissue examined except the kidney. The presence of Alpha2u globulin was further confirmed by radioimmunoassay. Also, Alpha2u had a direct stimulatory effect on the release of pituitary hormones in vitro and in vivo. These findings are extremely relevant because Alpha2u hepatic mRNA level, rate of hepatic biosynthesis and serum levels are known to be controlled by growth hormone and androgen, glucocorticoid, thyroid hormone; the latter 3 hormones are in turn controlled by anterior pituitary hormones. To our knowledge Alpha2u could be a unique system to study a possible liver-pituitary axis. Using immunocytochemistry (IC) and electron microscopy (TEM), we expect to be able to identify the pituitary cell types that contain Alpha2u and study its subcellular localization. This might help us elucidate its physiological role which is unknown. Using IC, TEM, autoradiography and radioreceptor binding assay we shall study its possible binding and internalization in anterior pituitary cells, and whether the characteristics of this eventual process (receptor-mediated endocytosis) are similar to those of other peptidergic and non-peptidergic hormones. Using radioimmunoassay and cell culture, we shall further study its effects on all pituitary hormone secretion and its interaction with other known pituitary secretalogues such as LHRH, TRH, somatostatin, dopamine and sex steroids. To extend these investigations, we shall also study whether a similar mouse urinary protein (MUP) known to be hormonally modulated is localized in the mouse anterior pituitary. More generally, the proposed studies would raise the question of whether other serum proteins, secreted by """"""""non-endocrine"""""""" tissues under pituitary control, are also present in the pituitary and might modulate pituitary hormone secretion. Because liver diseases such as cirrhosis and hepatoma, which generally induce a reduction in the hepatic biosynthesis of serum proteins, are often accompanied by endocrine abnormalities, this project which might give evidence for a liver-pituitary axis, might help us to explain such abnormalities.
