In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.

Abstract

Physiology/PharmacologyIn vitro effect of A9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2 (in vitro 2). The central site of action of THC is also supported by the finding that in vivo administration of THC elevated the LHRH content in the mediobasal hypothalamus (MBH) (1, 3) at a time when plasma LH levels were lowered. It is known that the release of LHRH is stimulated by noradrenergic terminals in the MBH that release prostaglandin E2 (PGE2). This in turn stimulates the release of LHRH. PGE2 increases LHRH release into peripheral (4, 5) and hypophyseal portal blood (6) and stimulates the release of LHRH from hypothalamic fragments (7). We hypothesized that the suppression of LH release by THC may be caused by a reduction of noradrenergic stimulation of PGE2 and LHRH release since THC was shown to reduce norepinephrine turnover in the MBH (3). The release of GH, which is also suppressed by THC, is controlled by GH-releasing hormone and somatostatin (SRIF), and SRIF release is inhibited by PGE2 (8).Consequently, the present experiments were performed to determine the mechanisms by which THC affects the release of LHRH and SRIF from median eminence fragments (MEs) in vitro. The effect of THC was evaluated under both basal conditions and during stimulation by catecholamines. Measurements of release of PGE2 and PGF2a and the metabolism of ['4C]arachidonic acid in the MBH were also performed in the presence and absence of THC. MATERIALS AND METHODSExperimental Animals. Male (Sprague-Dawley) rats (230-270 g) (Holtzman, Madison, WI) were used as tissue donors. They were housed in group cages (10 rats per cage) under controlled conditions of light (14 hr of light/10 hr of dark) and temperature (24 + 10C); rat chow and water were provided ad libitum.Experimental Procedures for Measurement of SRIF and LHRH. The rats were decapitated, their brains were removed, and MEs were dissected free under a stereoscopic microscope according to a described procedure (9). The tissue sample included only the ME and the proximal stump of the pituitary stalk. The MEs were incubated in KrebsRinger bicarbonate glucose buffer (pH 7.4) (KRBG) in an atmosphere of 95% 02/5% CO2 with constant shaking at 60 cycles per min at 370C. The ethanol solution of THC of >95% purity was provided by the National Institute of Drug Abuse.Immediately before use, the alcohol was evaporated under N2, and the residue was redissolved in a volume of ethanol such that the final ethanol concentration in the medium was 0.01%. The same concentration of ethanol was added to media of control flasks. Each flask contained one ME fragment in 500 ,Al of medium. In all cases, tissues were preincubated for 30 min, after which the medium was replaced by fresh medium containing different concentrations of THC (10 nM to 10 pM) and/or dopamine (50 ,uM) and/or norepinephrine (50 ,M). Both dopamine and norepinephrine were obtained from Sigma. PGE2 (Sigma) was added ...

Progesterone receptor and dopamine receptors are required in Δ 9 -tetrahydrocannabinol modulation of sexual receptivity in female rats

“…ICV administration of THC elevated LHRH content in the MBH within 30 min followed by a decrease at 60 min, concurrent with lowered plasma LH levels in male rats (53). In vitro studies indicated that the suppressive effect of THC on LH release was because of the reduction in noradrenergic stimulation of prostaglandin E 2 (PGE 2 ) and LHRH release in MBH (54). De Miguel et al (42) have provided evidence for a role of CB 1 receptors in the suppressive effects of THC on LH release.…”

Distribution of type 1 cannabinoid receptor (CB1)‐immunoreactive axons in the mouse hypothalamus

“…Exogenous administration of cannabinoids influences neuroendocrine axes, e.g., it stimulates the hypothalamic-pituitary-adrenal (HPA) axis through CB1 (Murphy et al, 1998) and inhibits the hypothalamicpituitary-thyroid, gonadal, and growth hormone axes (Lomax, 1970;Tyrey, 1978;Rettori et al, 1990;Pagotto et al, 2006). In addition, the endocannabinoid system also plays a critical role in the hypothalamic control of energy homeostasis (Pagotto et al, 2006).…”

Effects of CP 55,940 — agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas

“…Rettori et al [32] found in their study a reduced secretion of the growth hormone, both from the normal pituitary gland of man, as well as from cells of somatotropic adenomas, as an effect of cannabinoid activity, which the authors associated with stimulation of somatostatin release in the hypothalamus.…”