FIG. 3.

Pter bioavailability in brain and the pituitary gland and its effect on ACTH synthesis and POMC expression in AtT-20 cells. (A) Whole brain and pituitary gland levels of Pter after its i.v. administration (30 mg/kg) (n = 6–7 mice; *Significantly different p < 0.01, comparing hypophysis vs. whole brain levels). Data in (A) correspond to tissues obtained from nontumor-bearing mice (results obtained in A2058 or MeWo melanoma-bearing mice were not significantly different, not shown). (B) Effect of Pter on ACTH production by AtT-20 cells in a 24 h-period (measured between 24 and 48 h or between 48 and 72 h). (C) Effect of Pter on POMC expression and (D) POMC protein levels (72 h of culture time) in AtT-20 cells (n = 6 for B, C, and D; *Significantly different p < 0.01, comparing +Pter vs. controls). For the in vitro experiments (B, C, and D), Pter (15 μM, see under the Results section) and CRH (100 nM) were added at time 0 and every 24 h through the culture time and were present, after each addition, for only 30 min. After the 30-min period, culture flasks were washed out (thrice with PBS) and the medium was renewed (controls received identical treatment). POMC, proopiomelanocortin.