Effects of somatostatin on the growth hormone-releasing factor-induced growth hormone secretion in rats with electrical and chemical inhibitions of endogenous growth hormone-releasing factor and somatostatin.
Abstract The episodic pattern of growth hormone (GH) secretion of the male rat was simulated in rats exhibiting impaired GH-releasing factor (GRF) and Somatostatin (SRIF) secretion, by administering various combinations of human GRF-(1-44)NH(2) (hGRF) and SRIF. Electrical lesions of the arcuate nucleus resulted in a marked decrease in the amplitude of GH secretory bursts, while the administration of cysteamine (200 mg/kg) did not change the GH secretory profile in rats with arcuate nucleus lesions. Immunohistochemical examinations revealed a marked decrease of GRF and SRIF immunoreactivity in the median eminence of the cysteamine-treated rats with arcuate nucleus lesions. The intravenous injection of 5 mug of hGRF every 3 h caused equivalent surges of GH in the cysteamine-treated rats with arcuate nucleus lesions. The additional infusion of 4 mug/h of SRIF during the trough periods of GH secretion did not affect the amplitude of the GH surges. Hourly injection of 5 mug of hGRF caused transient desensitization to hGRF. Interestingly, the additional infusion of 4 mug/h of SRIF every 3 h enhanced the amplitude of the GH bursts induced by the fourth and the seventh hGRF injections. However, the more frequent injection of 5 mug of hGRF every 30 min caused constant desensitization to hGRF with time, and the additional infusion of 4 mug/h of SRIF every 3 h did not change the attenuated responses to hGRF. These results indicated that the simultaneous administration of hourly GRF and continuous SRIF with brief pauses was most effective for producing high GH peaks. This simulation model suggests that SRIF may play an important role not only in the production of GH troughs, but also in the maintenance of GH surges with distinct peaks in the male rat.
Sato
M
M
First Department of Internal Medicine, Kagawa Medical School, 1750-1, Miki-Cho, Kita-Gun, Kagawa, Japan.
Takahara
J
J
Niimi
M
M
Irino
S
S