We studied the effects of growth hormone to subthreshold, threshold, or suprathreshold dose of growth hormone-releasing hexapeptide (GHRP-6) in conscious and unconscious (anesthesized with ketamine and phenobarbital) female Sprague Dawley rats
with
hypothyroidism, induced with methimazole and compared these results with those in conscious and uncounscious rats with euthyroidism.
@ES The results were as below;
@EN 1) In conscious rate, the peak GH response to 10 g/kg of GHRP-6 was 4.8 0.5ng/ml and the peak GH response to 15 g/kg of GHRP-6 was 23.5 0.6ng/ml. With these results, we determined 10 g/kg as a subthreshold dose and 15 g/kg as threshold dose.
2) In conscious rats, the peak GH response to subthreshold dose, 10 g/kg was 17.2 1.8ng/ml in hypothyroid subgroup, which is significant higher than that (4.8 0.5ng/ml) in euthyroid subgroup(p<0.001). The peak GH response to suprathreshold dose,
100
g/kg, was 85.8 14.3ng/ml in hypothyroid subgroup, which is higher than that (185.1 14ng/ml) in euthyroid subgroup (p<0.001).
3) In unconscious rats, peak GH response to 1 g/kg of GHRP-6 was 9.0 2.5ng/ml and peak GH response to 3 g/kg of GHRP-6 was 52 13.9ng/ml. We determined 3 g/kg of GHRP-6 as threshold dose.
4) In Unconscious rats, the AUCs to the threshold dose of GHRP-6, 3 g/kg were 340.6 18.4ng/ml·min in hypothyroid subgroup and 830.8 346.4ng/ml·min in euthyroid group, which has borderline significant difference (p=0.05). In hypothyroid
unconscious
subgroup, there was no signficant difference between the GH responses to 3 and 6 g/kg of GHRP-6, but in euthyroid unconscious subgroup, there was borderline difference between the GH responses to 3 and 6 g/kg(p=0.05).
5) In unconscious rats, the AUCs to saline infusion were 382.4 35.1 ng/ml·min in hypothyroid subgroup and 262.5 20.5ng/ml·min in euthyroid subgroup, which has no significant difference. We could not observe any significant difference between GH
response to GHRP-6 in unconscious hypothyroid rats and GH response to saline in unconscious hypothyroid rats, but we could observe signficantly higher GH response to GHRP-6 in unconscious euthyriod rats, compared with that to saline in
unconscious
euthyroid rats (p<0.05).
With above results, it is suggested that the suppression of GH synthesis in hypothyroid state is partial and the increased GHRH from hypothalamus can synthesize the GH continuously, which stores in the somatotrophs and can be secreted by small
dose
of
GHRP-6 and this GH secretion is dose-dependent in hypothyroidism. But the exact mechanism by which GHRP-6 can secrete GH in hypothyroidism is remained to be studied.
In addition, it is suggested that hypothyroidism and anesthesizing agents could affect GH secretion by direct or indirect effect on the receptor to GHRP-6 or neurotansmitter.
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