Central administration of an antisense oligodeoxynucleotide against type I pituitary adenylate cyclase-activating polypeptide receptor suppresses synthetic activities of LHRH-LH axis during the pubertal process.

Central administration of an antisense oligodeoxynucleotide against type I pituitary adenylate cyclase-activating polypeptide receptor suppresses synthetic activities of LHRH-LH axis during the pubertal process In the present study, we determined the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP receptor type I (PAC1) genes during juvenile development and the pubertal process. Female rats were assigned--based on uterine weights, the presence and abundance of uterine fluid, and their vaginal patency--to one of the following: anestrus (AE), early proestrus (EP), late proestrus (LP) or first estrus (E). The hypothalami from 22-, 24- and 26-day-old animals and from those in the peripubertal phases of AE, EP, LP and E were collected, and the content of PACAP and PAC1 mRNA was assessed. These levels were found to decrease in EP and LP. To determine the effect of PACAP on prepubertal luteinizing hormone-releasing hormone (LHRH) and LH synthesis through PAC1, a PAC1 antisense oligodeoxynucleotide (ODN) was i.c.v.-administered, and mRNA levels of LHRH, LH beta, and LHRH receptor (LHRH-R) were determined. Prepubertal increases in LHRH, LH beta, and LHRH-R mRNA levels were markedly suppressed, and the onset of puberty was delayed by the i.c.v. injection of the antisense PAC1 ODN. These data suggest that PACAP may play a role in the regulation of hypothalamic LHRH neurons, through which it regulates synthetic machinery of pituitary LH, during the pubertal process.