The phospholipid drug glyceryl-phosphoryl-O-serine modulates pituitary adrenocorticotropin and hypothalamic corticotropin releasing hormone in vitro secretion in the aging rat.

Abstract

We have investigated the effects of the novel phospholipid drug glyceryl-phosphoryl-O-serine (GPS) on pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in vitro in cultures from both 2- and 24 month-old Sprague-Dawley rats. Basal levels of ACTH in primary cultures of pituitary cells from 24 month-old rats were lower than (100 +/- 12 pg/10(5) cells) in 2 month-old rats (207 +/- 18 pg/10(5) cells). Basal medium corticotropin releasing hormone levels in hypothalamic cultures were higher in 24 month-old rats (45 +/- 7 pg/well/20 min.), than in 2 month-old rats (29 +/- 5.5 pg/well/20 min). Treatment of both pituitary cells with corticotropin releasing hormone and hypothalami with serotonin resulted respectively in a significant, concentration-dependent, increase of medium ACTH and corticotropin releasing hormone. However, concentration-response curves for ACTH and corticotropin releasing hormone were shifted to the right in cultures from 24 month-old rats. Incubation with graded concentrations of GPS produced significant increase in medium ACTH and corticotropin releasing hormone in cultures from 24 month-old rats, whereas the drug was ineffective in stimulating secretion of both hormones from 2 month-old rat cells. In addition, the adenylate cyclase stimulator forskolin and the protein kinase C activator oleyl-acyl-glycerol stimulated ACTH secretion in pituicytes from rats of both ages. However, response to oleyl-acyl-glycerol was blunted in pituicytes from 24 month-old rats. Combination of either forskolin or oleyl-acyl-glycerol with GPS resulted in a potentiation of the effect. Our data confirm an impairment of both pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in the aging rat.(ABSTRACT TRUNCATED AT 250 WORDS)