Hormone Secretion In Rats Research Articles

Antihypercholesterolemic and Antioxidant Effects of Blumea balsamifera L. Leaf Extracts to Maintain Luteinizing Hormone Secretion in Rats Induced by High-Cholesterol Diets

BACKGROUND: The discovery of herbal ingredients for antihypercholesterolemic and to improve male reproductive function is very necessary due to high-cholesterol diet factors. Blumea balsamifera leaf extract (BBLE) is known to be able to increase the number and diameter of Leydig cells in rats given high-fat feed. This study was to conducted to determine the levels of total cholesterol, body weight, plasma malondialdehyde (MDA), Superoxide Dismutase (SOD), Luteinizing Hormone (LH) in high-cholesterol-fed male rats provided with BBLE.METHODS: This research utilized a randomized post-test only control group. Ethanol was used to extract the BBLE, which was then evaporated. For 21 days, 16 Wistar rats were given a high-cholesterol diet. To determine the effect of BBLE on the high-cholesterol diet, the samples were divided into two groups (control and BBLE group) on day 22. The treatments lasted 30 days. SOD, plasma MDA, LH, and total cholesterol were measured.RESULTS: The results showed that the SOD and LH parameters were significantly higher in the treatment of BBLE compared to the control group (p<0.05). The parameters of total cholesterol levels, bodyweight, and MDA of rats given BBLE were significantly lower than those of the control group (p<0.05).CONCLUSION: Our findings highlight that BBLE has antihypercholesterolemic and antioxidant effects. The BBLE also has potential to be used as a therapy to maintain male reproductive function because it has a positive effect on the hypothalamic-pituitary axis through increasing LH secretion.KEYWORDS: Malondialdehyde, Superoxide dismutase, Luteinizing hormone, Blumea balsamifera extract, High-cholesterol diet

Neuropeptide S increases motor activity and thermogenesis in the rat through sympathetic activation

The central role of neuropeptide S (NPS), identified as the endogenous ligand for GPR154, now named neuropeptide S receptor (NPSR), has not yet been fully clarified. We examined the central role of NPS for body temperature, energy expenditure, locomotor activity and adrenal hormone secretion in rats. Intracerebroventricular (icv) injection of NPS increased body temperature in a dose-dependent manner. Energy consumption and locomotor activity were also significantly increased by icv injection of NPS. In addition, icv injection of NPS increased the peripheral blood concentration of adrenalin and corticosterone. Pretreatment with the β1- and β2-adrenergic receptor blocker timolol inhibited the NPS-induced increase of body temperature. The expression of both NPS mRNA in the brainstem and NPSR mRNA in the hypothalamus showed a nocturnal rhythm with a peak occurring during the first half of the dark period. To examine whether the endogenous NPS is involved in regulation of body temperature, NPSR antagonist SHA68 was administered one hour after darkness. SHA68 attenuated the nocturnal rise of body temperature. These results suggest that NPS contributes to the regulation of the sympathetic nervous system.

Involvement of Neurokinin Receptors in the Control of Pulsatile Luteinizing Hormone Secretion in Rats

It has recently been shown that neurokinin B, a tachykinin, is associated with GnRH pulse generation in sheep and goats. The aim of the present study was to clarify the role of tachykinin receptors in the control of LH secretion in rats. To this end, we evaluated the effect of CS-003, an antagonist for all three neurokinin receptors (NK1, NK2 and NK3 receptors), on pulsatile LH secretion in both sexes of rats with different routes of administration. Both oral and third ventricular administration of CS-003 suppressed LH secretion in both sexes of gonadectomized animals. Furthermore, intact male rats with oral administration of CS-003 showed decreased serum testosterone levels, which might be due to suppressed LH secretion. None of the three subtype-specific neurokinin receptor antagonists showed a significant effect on LH secretion in ovariectomized rats when each antagonist was singly administered. The present results suggest that neurokinins play a role in the control of pulsatile GnRH/LH secretion via multiple neurokinin receptors in both male and female rats.

Role of urocortin 2 secreted by the pituitary in the stress-induced suppression of luteinizing hormone secretion in rats

We have previously shown that urocortin 2 (Ucn 2), a member of the corticotropin-releasing factor (CRF) peptide family that binds to CRF type 2 receptor, is expressed in proopiomelanocortin (POMC) cells of rat pituitary and that its secretion and expression are increased by CRF in both the anterior and intermediate lobes and suppressed by glucocorticoids in the anterior lobe. We have also shown that Ucn 2 secreted by POMC cells acts on gonadotrophs expressing CRF type 2 receptors and inhibits the expression and secretion of gonadotropins. In the present study, we examined whether pituitary Ucn 2 is involved in stress-induced inhibition of gonadotropin secretion. A 90-min period of immobilization stress increased POMC mRNA expression without influencing Ucn 2 mRNA expression and suppressed luteinizing hormone (LH) β-subunit mRNA expression in the anterior lobe and plasma LH levels, while it increased both POMC and Ucn 2 mRNA expression in the intermediate lobe of the pituitary. Pretreatment with anti-CRF IgG blocked immobilization-induced increases in plasma ACTH and corticosterone and in POMC mRNA expression in both pituitary lobes and Ucn 2 mRNA expression in the intermediate pituitary. It also blocked immobilization-induced suppression of plasma LH and LH β-subunit mRNA expression. Pretreatment with anti-Ucn 2 IgG blocked immobilization-induced suppression of plasma LH and LH β-subunit expression without affecting immobilization-induced ACTH and corticosterone release and POMC or Ucn 2 mRNA expression. These results suggest that CRF suppresses the secretion and expression of LH probably through pituitary Ucn 2 in stress.

The effect of Glutamine- enriched Enteral Nutrition on Metabolic Hormone secretion in rats with severe head injury

目的 探讨谷氨酰胺强化的肠内营养对大鼠重型颅脑损伤后代谢激素分泌的影响.方法 采用重度颅脑损伤大鼠模型,40只SD雌雄性大鼠随机分为3组:正常对照组(C组);肠内营养组(EN组);肠内营养添加Gln组(Gln组).C组8只动物,其余各组16只.C组不致伤,其余2组于致伤后4 h开始灌胃等氮、等热卡的肠内营养制剂.第1天给予半量71.49 kcal/(kg·d),第2天给予全量142.97 kcal/(kg·d),每天2次.连续灌喂第3、7天后,取外周血标本,应用放射免疫法检测血清胰岛素(INS)、胰高血糖素(GIU)、皮质醇(Cor)含量.结果 伤后第3、7天EN组和Gln组的INS/GLU较C组非常显著的下降(P＜0.01),Cor含量则非常显著升高(P＜0.01).Gln组的INS/GLU在第3天和EN组无统计学意义(P＞0.05),到了第7天明显高于EN组(P＜0.05).Gln组的Cor含量在各时相点都非常显著低于EN组(P＜0.01).结论 重型颅脑损伤后大鼠出现明显的代谢激素分泌紊乱,添加Gln的肠内免疫营养可促进机体合成代谢激素分泌,降低分解代谢激素释放。

Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

A series of ghrelin receptor ligands based on the trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the significance of the aminoisobutyryl (Aib) moiety, a common feature in numerous growth hormone secretagogues described in the literature. Potent agonist and antagonist ligands of the growth hormone secretagogue receptor type 1a (GHS-R1a) were obtained, i.e., compounds 41 (JMV2894) and 17 (JMV3031). The best compounds were evaluated for their in vivo activity on food intake, after sc injection in rodents. Among the tested compounds, few of them were able to stimulate food intake and some others, i.e., compounds 4 (JMV2959), 17, and 52 (JMV3021), acted as potent in vivo antagonist of hexarelin-stimulated food intake. These compounds did not stimulate growth hormone secretion in rats and furthermore did not antagonize growth hormone secretion induced by hexarelin, revealing that it is possible to modulate food intake without altering growth hormone secretion.

High-phosphorus diet stimulates receptor activator of nuclear factor-κB ligand mRNA expression by increasing parathyroid hormone secretion in rats

The purpose of the present study was to clarify the manner by which the supplementation of high-P diet induces bone loss. Eighteen 4-week-old male Wistar-strain rats were assigned randomly to three groups and fed diets containing three P levels (0.3, 0.9, and 1.5 %) for 21 d. A lower serum Ca concentration was observed in the rats fed on the 1.5 % P diet than in the other two groups. Serum P and parathyroid hormone concentrations and urinary excretion of C-terminal telopeptide of type I collagen were elevated with increasing dietary P levels. Serum osteocalcin concentration was increased in the rats fed on the 1.5 % P diet than in the other two groups. Bone formation rate of the lumbar vertebra was significantly increased in the two high-P groups than in the 0.3 % P group. Osteoclast number was significantly increased with increasing dietary P levels. Bone mineral content and bone mineral density of the femur and lumbar vertebra and ultimate compression load of the lumbar vertebra were decreased with increasing dietary P levels. Additionally, ultimate bending load of the femur was decreased in the rats fed on the 1.5 % P diet than in the other two groups. Receptor activator of NF-kappaB ligand (RANKL) mRNA expression in the femur was significantly higher with increasing dietary P levels. These results suggest that secondary hyperparathyroidism due to a high-P diet leads to bone loss via an increase in bone turnover. Furthermore, an increase in osteoclast number was caused by increased RANKL mRNA expression.

Glucocorticoid counteracts the suppressive effect of tumor necrosis factor-alpha on the surge of luteinizing hormone secretion in rats

We have previously reported that tumor necrosis factor-alpha (TNF-alpha) suppressed pulsatile secretion of luteinizing hormone (LH) in adrenalectomized (ADX) rats, which was restored by replacement of glucocorticoid. In the present study, we examined the role of glucocorticoid in inducing the preovulatory LH surge under conditions of infectious stress. Intravenous injection of TNF-alpha (1 microg) into the proestrous rats at 1300 h attenuated the LH surge and decreased the number of oocytes ovulated. The inhibitory effect of TNF-alpha on the LH surge was blocked by pretreatment with indomethacin, suggesting that the effects of TNF-alpha were mediated by prostaglandins (PGs). On the other hand, ADX markedly enhanced the inhibitory effect of TNF-alpha on the LH surge and subsequent ovulation, which was almost completely restored by pretreatment with a subcutaneous injection of corticosterone (10 mg). These results suggest that glucocorticoid counteracts the inhibitory effect of the cytokines on the preovulatory LH surge by suppressing PG synthesis, and thereby helps to maintain reproductive function under infectious stress conditions.

Evaluation of the Role of Melanocortin 3 and 4 Receptors in Leptin-Stimulated and Spontaneous Growth Hormone Secretion in Rats

It has been reported that the melanocortin 4-receptor (MC4-R) may act downstream of leptin to mediate its effects on food intake and several neuroendocrine functions (the reproductive system, the hypothalamo-pituitary-thyroid axis, and prolactin secretion). However, no previous study examined whether MC4-R mediates leptin stimulatory actions on growth hormone (GH) secretion, or whether MC4-R signaling is involved in spontaneous pulsatile GH release in fed rats. Therefore in this study we examined the involvement of both MC3-R and MC4-R (the predominant MC-R subtypes expressed in the brain) in these two aspects of GH secretion in freely-moving male rats. In both fed and 3-day fasted rats, plasma GH levels were determined every 15 min over 5 h after single intracerebroventricular injections of the following substances or vehicle. Fasting diminished and leptin (0.3 nmol) reinstated the GH pulse amplitude without affecting the pulse frequency. Neither HS014 (1.0 nmol, a selective MC4-R antagonist) nor agouti-related peptide (1.0 nmol, a non-selective MC3/4-R antagonist) was effective in altering leptin-stimulated or spontaneous GH secretion. In addition, neither melanotan-II (1.0 nmol, a non-selective MC3/4-R agonist) nor γ₁-melanocyte-stimulating hormone (10 nmol, a selective MC3-R agonist) affected significantly GH release in fasted rats. We have previously demonstrated that stimulation or blockade of MC4-R, achieved by the same drug dosage as in this study, significantly affect luteinizing hormone and prolactin secretion in rats. The present results thus suggest that neither MC4-R nor MC3-R is involved in leptin-stimulated or spontaneous GH secretion, or at least that the level of MC4-R involvement in GH secretion is much lower than that in luteinizing hormone and prolactin release regulation.

Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet.

Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg.kg-1.day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.

The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats

Background & Aims: Visceral sensory information is transmitted to the brain through the afferent vagus nerve. Ghrelin, a peptide primarily produced in the stomach, stimulates both feeding and growth hormone (GH) secretion. How stomach-derived ghrelin exerts these central actions is still unknown. Here we determined the role of the gastric afferent vagal nerve in ghrelin's functions. Methods: Food intake and GH secretion were examined after an administration of ghrelin intravenously (IV) to rats with vagotomy or perivagal application of capsaicin, a specific afferent neurotoxin. We investigated Fos expression in neuropeptide Y (NPY)-producing and growth hormone–releasing hormone (GHRH)-producing neurons by immunohistochemistry after administration IV of ghrelin to these rats. The presence of the ghrelin receptor in vagal afferent neurons was assessed by using reverse-transcription polymerase chain reaction and in situ hybridization histochemistry. A binding study on the vagus nerve by 125I-ghrelin was performed to determine the transport of the ghrelin receptor from vagus afferent neurons to the periphery. We recorded the electric discharge of gastric vagal afferent induced by ghrelin and compared it with that by cholecystokinin (CCK), an anorectic gut peptide. Results: Blockade of the gastric vagal afferent abolished ghrelin-induced feeding, GH secretion, and activation of NPY-producing and GHRH-producing neurons. Ghrelin receptors were synthesized in vagal afferent neurons and transported to the afferent terminals. Ghrelin suppressed firing of the vagal afferent, whereas CCK stimulated it. Conclusions: This study indicated that the gastric vagal afferent is the major pathway conveying ghrelin's signals for starvation and GH secretion to the brain.GASTROENTEROLOGY 2002;123:1120-1128

Effects of dopamine and dopamine-active compounds on oxytocin and vasopressin production in rat neurohypophyseal tissue cultures

The effects of dopamine (DA) or DA-active drugs on the synthesis of neurohypophyseal (NH) hormones were studied in 13–14 day cultures of isolated NH tissue from rats. The following DA-active compounds were used (10 −6 M in each medium): DA, apomorphine (APM), Pro-Lys-Gly (PLG), butaclamol (B), haloperidol (HP), chlorpromazine (CPZ) and sulpiride (SP). The oxytocin (OT) and vasopressin (VP) contents of the condensed media were determined by RIA after a 1 or 2 h incubation. Significantly increased contents of OT and VP were detected in the tissue culture media following DA, APM or PLG administration. This elevation of NH hormone production could be blocked by previous administration of B or the DA receptor antagonists HP, CPZ or SP. The application of B after DA agonists proved ineffective. The results indicate that NH hormone production can be directly influenced by the DA-ergic system. The DA-ergic control of NH hormone secretion in rats can occur independently of the hypothalamus, at the level of the posterior pituitary.

Water ingestion provides an early signal inhibiting osmotically stimulated vasopressin secretion in rats.

Dehydrated dogs are known to inhibit secretion of vasopressin (VP) within minutes after drinking water, before plasma osmolality (P(osmol)) diminishes. The present studies determined whether water ingestion causes a similar rapid inhibition of neurohypophyseal hormone secretion in rats. Adult rats were infused with 1 M NaCl (2 ml/h iv) for 240 min to stimulate VP and oxytocin (OT) secretion. After 220 min of infusion, rats were given water to drink for 5 min, and blood samples were taken 5 and 15 min later for RIA. Plasma VP (pVP) was much lower when rats ingested water than when they drank nothing even though P(osmol) was not significantly altered. Plasma OT (pOT) was affected similarly. In contrast, no effects on pVP or pOT occurred when rats drank isotonic NaCl solution for 5 min in amounts comparable to the water intakes (approximately 5.5 ml). These results suggest that neurohypophyseal secretion of VP and OT in rats is inhibited rapidly by water drinking, and that this inhibition is mediated by a visceral signal of osmotic dilution rather than by the act of drinking per se.

Adrenocorticotropic hormone secretion in rats induced by stimulation with serotonergic compounds. hsj@mfi.ku.dk.

The serotonin receptors involved in the secretion of adrenocorticotropin hormone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5-HT), 5-hydroxytryptophan (5-HTP) in combination with the serotonin reuptake inhibitor fluoxetine (Flx), or of the 5-HT agonists 8-OH-DPAT (5-HT1A), 5-carboxamido-tryptamine (5-HT1A+1B+5A+7), RU 24969 (5-HT1B+1A), DOI (5-HT2A+2c), S-alpha-methyl-5-HT (5-HT2A+2B+2c), MK212 (5-HT2B+2c), or methyl-chlorophenyl-piperazine (5-HT2A+2c) dose-dependently stimulated ACTH secretion. The 5-HT3 agonist 2-methyl-5-HT had no effect. Administration of a 5-HT1 agonist in combination with any of the 5-HT2 agonists DOI, S-alpha-methyl-5-HT or MK212 had an additive effect on the plasma concentration of ACTH. The ACTH stimulating effect of each of the 5-HT agonists was inhibited by pretreatment with antagonists with corresponding 5-HT receptor affinity. The ACTH response to 5-HT or 5-HTP/Flx was inhibited by injection with the 5-HT1A+2A+2c+5A+7 antagonist methysergide, the 5-HT2A antagonist ketanserine and the 5-HT2C+2A antagonist LY 53857. The 5-HT1A antagonist WAY 100635 enhanced 5-HT- and 5-HTP/Flx-induced ACTH secretion, suggesting a presynaptic 5-HT1A autoreceptor effect of the drug. The 5-HT3 antagonist ondansetrone had no effect on the either of the 5-HT agonists. The 5-HT3+4 antagonist tropisetrone attenuated the effect of 5-HTP/Flx, which may suggest a stimulation of ACTH secretion via 5-HT4 receptors. It is concluded that 5-HT1A, 5-HT2A+2C, and to a lesser extent 5-HT1B receptors, but not 5-HT3 receptors are involved in the effects of serotonin agonists on ACTH secretion. Furthermore, an involvement of the 5-HT5A and the 5-HT7 receptor is possible.

Evidence for a dual function of oxytocin in the control of growth hormone secretion in rats

The aim of the present study was to investigate the role of oxytocin (Oxy) in the control of growth hormone (GH) release. Oxy was administered subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) to male rats. The animals were decapitated and trunk blood was collected at 30 and 120 min after Oxy administration. GH levels were analyzed by radioimmunoassay. Oxy (100 μg, s.c) increased plasma levels of GH significantly 30 min after administration. Oxy (2 ng, i.c.v.) caused a significant rise of GH after 120 min. This effect was completely abolished by previous administration of the Oxy antagonist 1-deamino-2- d-Tyr-(OEt)-4-Thr-8-Orn-oxytocin. When 5 μg of Oxy were given i.c.v. or 1 mg s.c., an inhibition of GH secretion was seen after 120 min. This effect was also abolished by the Oxy antagonist. Thus Oxy may influence GH in opposite directions depending on the doses given.

Inhibitory effect of neuropeptide Y on growth hormone secretion in rats is mediated by both Y1- and Y2-receptor subtypes and abolished after anterolateral deafferentation of the medial basal hypothalamus

Neuropeptide Y (NPY) may play a physiological role in the regulation of growth hormone (GH) secretion by acting via somatostatin (SS) in the periventricular nucleus (PeV), as well as via the GH-releasing factor in the arcuate nucleus (ARC) of the medial basal hypothalamus (MBH). The objectives of the present study were to determine the neuron structures and receptor subtypes necessary for mediating the inhibitory effect of NPY on GH secretion in unanesthetized male rats. To eliminate the influence of hypophyseotropic SS, anterolateral deafferentation (ALC) of the hypothalamus was performed. Intracerebroventricular (i.c.v.) administration of 1.17 nmol of NPY decreased the blood level of GH for 3–4 h in sham-operated rats, while the procedure was without effect in ALC rats. The i.c.v. administration of 1.17 nmol of a Y1-receptor agonist ([Leu 31, Pro 34]-NPY) or a Y2-receptor agonist (NPY 13–36 and NPY 3–36) similarly suppressed the blood GH level. The data support the hypothesis that neuron structures anterolateral to the MBH are required for NPY-induced inhibition of GH secretion that is mediated via Y1- and Y2- receptor subtypes. Combined with data of other investigators, SS is likely the neurohumoral mediator of the effect of NPY on GH secretion.

Impact of uraemia on food efficiency and the pulsatile mode of growth hormone secretion in rats.

In view of the profound growth failure resulting from renal insufficiency and uraemia, the present studies were designed to specifically investigate food efficiency and the pattern of GH secretion under these conditions. Animals were made uraemic by 5/6 nephrectomy (Nx) and feeding a high-protein diet. Three groups of animals were studied: uraemic (Ur); sham-operated, fed ad libitum (Sh); and sham-operated pair-fed with the uraemics (PF). Food intake per 100 g body weight and food efficiency (g weight gained per g food consumed) were calculated. Fourteen days after 5/6 Nx, blood samples were taken via intra-atrial catheters at 10-min intervals over a period of 6 h. GH was measured in plasma by radioimmunoassay. GH pulsatility was analysed by multiple parameter deconvolution. The growth rate of Ur animals was significantly lower than that of Sh. The body weights of the Ur animals were also lower than PF due to an initial period of weight loss. Both Sh and PF animals showed the typical negative slope of food intake as body weight increased. In contrast, the Ur animals showed a positive slope of food intake. The lower rate of growth and the elevated food intake corresponded to a decreased food efficiency for the Ur group. Deconvolution analysis of pulsatile GH release demonstrated a significant increase in GH half-life in the Ur animals. The amplitude and mass of GH secretory pulses were decreased, whereas the number of detectable secretory bursts was increased. These changes were specific to uraemia with respect to half-life and number of pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

μ- and δ-opioid receptor antisense oligodeoxynucleotides antagonize morphine-induced growth hormone secretion in rats

Effects of i.c.v. pretreatment with antisense oligodeoxynucleotides (antisense oligos) targeted against either μ- or δ-opioid receptors on morphine-induced release of growth hormone (GH) and prolactin were studied in male rats. The stimulation of GH secretion by i.c.v. morphine was completely inhibited by the antisense oligo targeted against the cloned μ-opioid receptor and significantly reduced by the antisense oligo targeted against the cloned δ-opioid receptor. The antisense oligo targeted against the cloned μ-opioid receptor, but not that targeted against the cloned δ-opioid receptor, abolished the stimulatory effect of acute morphine on prolactin secretion. It is concluded that both the GH and prolactin secretion stimulating effect of morphine is mainly mediated by the cloned μ-opioid receptor. Further, the cloned δ-opioid receptor is involved in the morphine-induced stimulation of GH secretion.

Carbamazepine effects on preoptic GABA release and pituitary luteinizing hormone secretion in rats.

In vivo effects of carbamazepine (CBZ) on the neuroendocrine preopticopituitary feedback system were studied by local application of CBZ through a push-pull cannula into the preoptic area and measurement of local effects on gamma-aminobutyric acid (GABA) and distant effects on a subsequent biologic response: luteinizing hormone (LH). Perfusion with 8 and 12 micrograms CBZ/ml cerebrospinal fluid caused a reduction in preoptic GABA release and concomitant suppression of plasma LH levels. These results suggest a GABA component to the mechanism(s) of action of CBZ: (a) CBZ reduces extracellular available GABA concentration, and (b) owing to the known inhibitory role of preoptic GABA in pituitary LH secretion, an increase of postsynaptic GABAergic transmission by CBZ itself could be inferred.

Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation

To test the hypothesis that growth retardation in nonanion gap acidosis may be associated with impairment of growth hormone (GH) secretory patterns, we examined GH secretion in rats made acidotic with ammonium chloride ingestion. Considerable growth retardation was demonstrated in pair-fed and acidotic rats after 1 wk of ammonium chloride ingestion compared with control. With stable metabolic acidosis sustained on the 8th day of experiment, pulsatile secretion of GH was evaluated by blood samples drawn every 10 min for 6 h. Using deconvolution analysis to quantitate in vivo GH secretory rates, we found significant inhibition of pulsatile GH secretion in acidotic rats. Changes in amplitude of GH pulses and mean mass of GH pulses correlated with changes in body weight. These studies showed that chronic metabolic acidosis causes growth impairment, reduced food efficiency, and amplitude-specific inhibition of pulsatile secretion of GH. We propose that this GH axis suppression, whether mediated by decreased nutrients or not, contributes significantly to growth failure in children with renal tubular acidosis. Because a similar degree of inhibition of GH secretion was seen in pair-fed rats, we infer that insufficient calorie intake in metabolic acidosis may contribute to disruption of normal GH secretion patterns. These changes in GH secretion were specific, because acidotic rats were different from pair-fed controls in that they showed no change in either half-life of GH in circulation or in pulse frequency. Such observations offer a rationale for more detailed clinical investigations into the impact of metabolic acidosis on physiological regulation of pulsatile GH secretion in humans.