Study of enteral versus parenteral application of the gonadotropin releasing hormone agonist Gonadorelin[6-D-Phe] (D-Phe6-LHRH) on LH secretion in Goettinger miniature pigs

Abstract

With respect to the assessment of residue situation and as a part of preclinical trials to determine the biological activities of potential gonadotropin releasing hormone (GnRH) residues in porcine organisms the GnRH agonist Gonadorelin[6-D-Phe] (D-Phe6-LHRH) was administered either enterally or intramuscularly (i.m.) to female Goettinger miniature pigs in order to evaluate the GnRH-induced luteinizing hormone (LH) surge. Gilts received an (i) enteral application of 10 mg D-Phe6-LHRH via a probang (enteral group, n=7), (ii) i.m. injection of 0.1 mg D-Phe6-LHRH (parenteral group, n=5), or (iii) saline injection (control group, n=4). The GnRH and saline applications were repeated every second day with up to seven repetitions. Blood samples were collected via previously fitted jugular catheters immediately before injections, over an 8 h period in 1 h intervals beginning 2 h after injections, and at 24, 26, 28 and 30 h after applications. Enteral application of D-Phe6-LHRH induced an LH surge in 23 of 30 treatments. All gilts in the parenteral group exhibited LH release after each D-Phe6-LHRH application (P<0.05), whereas no LH surges were observed after saline injection in the control group. A significant (P<0.05) LH rise to mean maximum LH concentrations of 3.25 ± 0.43 and 3.05 ± 0.26 ng/ml occurred in both the enteral and parenteral groups, but there was no difference in the time interval after GnRH (2.6 ± 0.3 vs. 2.3 ± 0.3 h) and the mean duration of LH peak (6.5 ± 0.4 and 6.8 ± 0.3 h) between the treatment groups. In conclusion, (i) enteral application of 10 mg D-Phe 6-LHRH induced LH release in a physiological range from the pituitary of female minipigs, and (ii) neither an accumulative effect nor a cumulative LH response were found after repeated GnRH application. Furthermore, (iii) in regard to consumer protection and gonadotropin secretion, D-Phe6-LHRH residues can be excluded from having long-term effects.