Effects of systemic GHRH on sleep in intact and hypophysectomized rats

Abstract

The role of pituitary growth hormone (GH) in the mediation of enhanced sleep elicited by GH-releasing hormone (GHRH) was studied in the rat. Intact and hypophysectomized (HYPOX) rats received systemic injections of GHRH or physiological saline. GHRH (0.5, 5.0, or 50 micrograms/kg in the intact rats and 0.5 or 50 micrograms/kg in HYPOX rats) was injected 6 h after light onset (P.M. injection) or just before light onset (A.M. injection, 0.5 microgram/kg in both A.M. groups). Sleep-wake activity and brain cortical temperature were recorded for 23 h (12 h light + 11 h dark). A.M. injection of GHRH did not alter sleep in normal or HYPOX rats. Each dose of P.M. GHRH increased rapid-eye-movement sleep (REMS) during 6 h postinjection in the intact rats. Hypophysectomy abolished the REMS-promoting activity of GHRH. P.M. injection of 0.5 microgram/kg GHRH increased non-REM sleep (NREMS) and enhanced electroencephalogram slow-wave activity during NREMS in both the intact and the HYPOX rats. The NREMS-promoting activity disappeared when the dose of GHRH was increased in the intact rats, whereas a tendency to enhanced NREMS was still observed after 50 micrograms/kg GHRH in the HYPOX rats. GHRH stimulated GH secretion dose dependently in the intact rats. A.M. injection of 0.5 microgram/kg GHRH tended to be less effective in stimulating GH release than the same dose administered P.M. The results confirm the time-of-day variations in the GHRH effects on sleep previously reported in human subjects. It is likely that pituitary GH is involved in the mediation of the REMS-promoting activity of GHRH but not in the NREMS-promoting activity of GHRH. Nevertheless, the results do not exclude the possibility that GH may modulate NREMS.

Central effects of the somatotropic system

“…REM sleep is also stimulated by GHRH in normal rats but not in hypophysectomized rats (152). Thus non-REM sleep appears to be directly stimulated by GHRH, whereas REM sleep seems to be mediated by GH but not by GHRH.…”

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

“…GHRH displays the best-documented sleeppromoting activity. NREMS increases after GHRH is injected into the cerebral ventricles (Ehlers et al, 1986;Nistico et al, 1987;Obál et al, 1988), into the medial preoptic area in rats (Zhang et al, 1999b), or systemically (Steiger et al, 1992;Kerkhofs et al, 1993;Marshall et al, 1999;Obál et al, 1996), and in response to GHRH-containing nasal spray (Perras et al, 1999). NREMS decreases when GHRH is inhibited by means of a competitive receptor antagonist (Obál et al, 1991) or by the activation of the negative feedback in the somatotropic axis, e.g., after high doses of GH (Mendelson et al, 1980), IGF-1 , or after somatostatinergic stimulation (Frieboes et al, 1997;Beranek et al, 1999).…”

Peripheral Injection of Chicken Growth Hormone-Releasing Hormone Inhibits Feeding Behavior in Chicks

“…However, there remained a possibility that GHRH47 might induce abnormal behavior such as sleeping in chicks, and thereby inhibit feeding behavior as the side effect. Indeed, the injection of GHRH promotes non-rapid eye movement sleeping in rats (Obál et al, 1996). In addition, the injection of anti-GHRH antibody suppresses spontaneous sleeping, demonstrating that GHRH is related to sleeping in rodents (Obál et al, 1996).…”

“…Indeed, the injection of GHRH promotes non-rapid eye movement sleeping in rats (Obál et al, 1996). In addition, the injection of anti-GHRH antibody suppresses spontaneous sleeping, demonstrating that GHRH is related to sleeping in rodents (Obál et al, 1996). Furthermore, GHRH-deficient mice shows increase in activity and decreased anxiety-and depression-related behavior (Leone et al, 2014).…”