The effect of maternal somatostatin administration from days 14 to 20 of gestation was examined. Fetal body growth was unchanged but brain cell DNA synthesis per gram of tissue decreased. Maternal serum levels of growth hormone and brain trophin were elevated following treatment conclusion. It was suggested that this was a rebound phenomenon and that short term blockade of pituitary growth hormone release during somatostatin treatment had impaired fetal brain cell DNA synthesis.
5-Hydroxy-L-tryptophan is a potent stimulus for growth hormone (GH) secretion in normal rats. This stimulus is completely blocked by melatonin and also by the serotonin antagonist, cyproheptadine.Materiala ancl Methods Groups of non-handled male and female Wistar rats 80 days old were injected intraperitoneally with the following drugs or drug combinations dissolved in 0.5 ml physiological saline containing 20% v/v ethanol: 5-hydroxy-L-tryptophan (5-HTP, 10 mg/kg); 5-HTP (10 mg/kg) plus melatonin (80 mg/kg); 5-HTP (10 mg/kg) plus cyproheptadine (10 mg/kg). Thirty minutes later the rats were decapitated and their blood collected. The serum level of radioimmunoassayable (RIA) GH of each rat was determined in the one assay using materials supplied by Dr. A Parlow (NIAMD, Rat Pituitary Hormone Program). The assay had a lower level of sensitivity of 4 ug/ml, a within assay precision (95% confidence limits) at 15 ng/ml of ± 8 ng and at 120 ng/ml ± 42 ng. Data were evaluated statistically using Student's t-test.
ResultaThe GH responses and serum GH levels of male and female rats receiving the same treatment were virtually identical and the results for both sexes are combined in the Figure. S-HTP caused a highly signi!icant elevation of RIA GH (p < 0.0005). i l z " i 10 E ~ • • 10 Figure .... •• 10 COilTlIOLI . •• 13 I-NTP + Mn ••• I-NTP + CypThis effect was completely blocked by the simultaneous administration of melatonin (MEL) or cyproheptadine (CYP). 5-HTP Vs 5-HTP+MEL, p < 0.0005 and 5-HTP Vs 5-HTP+CYP, P < 0.0005. The level of GH achieved by 5-HTP+MEL was not signi!icantly different from the controls, but with 5-HTP+CVP the level was significantly lower than controls (p < 0.05). The serum RIA rat GH levels for each test group (± SEM) are shown in the Figure. "n" refers to the number of animals in each group.
DiIcussionThe observation that 5-HTP, which elevates brain serotonin levels, is a potent stimulus for rat GH secretion supports the postulate that rat GH is released via serotoninergic pathways (Collu, FralJchini, Visconti and Martini 1972). The data show this stimulus to be blocked by the serotonin antagonist cyproheptadine and more importantly, by melatonin. We propose that the pineal gland is an important regulator of GH secretion, exerting inhibitory (melatonin) control via the hypothalamo-pituitary axis.
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