The Phospholipid Drug Glyceryl‐phosphoryl‐O‐serine Modulates Pituitary Adrenocorticotropin and Hypothalamic Corticotropin Releasing Hormone in vitro Secretion in the Aging Rat

We have investigated the effects of the novel phospholipid′ yceryl‐phosphoryl‐O‐serine (GPS) on pituitary ACTH and hypothalamic corticotropin releasing hormone secreti ro in cultures from both 2‐ and 24 month‐old Sprague‐Dawley rats. Basal levels of ACTH in primary cultures o′ cells from 24 month‐old rats were lower than (100±12 pg/105 cells) in 2 month‐old rats (207±18 pg/105 cells). 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. Results suggest that defi‐citary signal transduction is possibly among causes of such impairment. Phospholipid drugs, such as GPS, appear to possess modulating effects on both pituitary ACTH and hypothalamic corticotropin releasing hormone