1-Methylhydantoin Inhibits The Secretion Of Growth Hormone In Rabbits

Objective: To explore whether 1-methylhydantoin(MH) could inhibit the basal secretion of growth hormone(GH) and suppress the promoting effect of growth hormone-releasing hormone(GHRH) in rabbits. Thus to verify whether 1-methylhydantoin had the fundamental function of somatostatin and provide experimental theory for the research and development of non-peptide somatostatin analogues.Methods: 36 rabbits were randomly divided into six experimental groups according to the kinds of dosing drugs, namely normal saline group(A), MH group(B), octreotide group(C), GHRH group(D), GHRH + MH group(E), GHRH + octreotide group(F), with 6 rabbits in each group. Each rabbit in A group was administrated normal saline 2.0 m L by intravenous injection, and 50 mg/m L MH solution 2.0 m L in B group, 5 ?g/m L octreotide solution 2.0 m L in C group, 5 ?g/m L GHRH solution 2.0 m L in D group, 10 ?g/m L GHRH solution 1.0 m L and 100 mg/m L MH solution 1.0 m L in E group, 10 ?g/m L GHRH solution 1.0 m L and 10 ?g/m L octreotide solution 1.0 m L in F group. Blood was sampled(1.0 m L each time) from each rabbit before injecting drugs and 5 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes after drug administration. Clotting spontaneously, rabbits blood samples were centrifugated for 20 minutes at approximately 1000×g and the supernatant was collected. Serum GH concentrations were determined by enzyme linked immunosorbent assay kit(ELISA Kit). The GH level variation of each group and each time point was compared to see if there were statistical significance.Results: 1. The GH level of rabbits in A group at each time point had no significant differences(P>0.05), suggesting that the basic GH level of rabbits had little fluctuation at 14:00-16:30. 2. The serum GH level began to go down about 5 minutes after the rabbits were administrated 100 mg MH through intravenous injection and reached to the low ebb at about 30 minutes. The action time of MH may exceed 60 minutes. 3. The serum GH level began to go up about 5 minutes after the rabbits were administrated 10 ?g GHRH through intravenous injection and reached to the peak at about 15 minutes. The action time of GHRH may maintain 60 minutes. 4. B group and C group rabbits GH levels were significantly lower than A group(P<0.05), while GH levels in D group rabbits were obviously higher than A group(P<0.05), indicating that 1-methylhydantoin and octreotide could inhibit the basal secretion of GH and GHRH could promote the secretion of GH in rabbits. 5. Compared with D group, rabbits GH levels in E group and F group decreased markedly(P<0.05), suggesting that 1-methylhydantoin and octreotide could suppress the promoting effect of GHRH in rabbits. 6. No obvious toxic and side effects had been observed within one week after the experimental rabbits were administrated corresponding drugs by intravenous injection, suggesting that MH had low toxicity.Conclusions: 1. 1-Methylhydantoin could inhibit the basal secretion of GH in rabbits. 2. 1-Methylhydantoin could suppress the promoting effect of GHRH in rabbits.