Luteinizing hormone, follicle stimulating hormone and prolactin secretion in ewes and wethers after zeranol or estradiol injection

Plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) were determined over a 24-h period using radioimmunoassay in sheep injected with corn oil (control) or various doses of zeranol or estradiol-17 beta. Injection of .333, 1 or 10 mg of zeranol caused dose-related increases (P less than .01) in plasma PRL (peak levels at 12 to 18 h) and LH (peak levels at 12 to 20 h) in ovariectomized ewes. Similarly, PRL and LH increased following doses of 33 or 100 microgram of estradiol. Before the LH surge, plasma LH levels were significantly depressed (4 to 8 h). Plasma FSH levels were significantly decreased 4 to 8 h after zeranol and estradiol injection. Slight surges of FSH were observed at times similar to those of LH, but the peak level was never greater than control levels. Injection of 1 mg of zeranol or 100 microgram of estradiol into wethers resulted in a 24-h pattern of PRL secretion not significantly different of LH concentration and significantly prolonged inhibition of FSH secretion. These results indicate similarities in the effects of zeranol and estradiol on anterior pituitary hormone secretion within groups of animals of the same sex or reproductive state. Differences in secretion and plasma concentrations of LH, FSH and PRL due to underlying sexual dimorphism are maintained and expressed even when animals are challenged with structurally different compounds of varying estrogenic potencies.     

Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells

A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.     

The neurophysiological regulation of growth hormone secretion

With the advent of genetic engineering, the importance of GH in the regulation of growth and metabolism in domestic species has been clearly demonstrated. Ample evidence of an integral role for GH in the processes of growth and lactation exists in dairy cattle (1,2), sheep (3), beef cattle (4) and swine (5). For example, circulating GH levels are high during the period of rapid growth in several species including cattle (6), swine (7) and poultry (8). Endogenous GH secretion is primarily controlled by the central nervous system (CNS) via two specific hypothalamic neurohormones, growth hormone-releasing factor (GRF) and somatostatin (SRIF), an inhibitor of GH release. The secretion of GRF and SRIF is governed by a host of neuropeptides and neurotransmitters which provide a functional link between higher CNS centers and hypophysiotropic neurons. This review will focus on the CNS regulation of GH secretion and circulating factors which feedback to either stimulate or inhibit its release.     

Orexin-B modulates luteinizing hormone and growth hormone secretion from porcine pituitary cells in culture

To test the hypothesis that orexin-B acts directly on the anterior pituitary to regulate LH and growth hormone (GH) secretion, anterior pituitary cells from prepuberal gilts were studied in primary culture. On day 4 of culture, 10(5) cells/well were challenged with 0.1, 10 or 1000 nM GnRH; 10, 100 or 1000 nM [Ala15]-hGRF-(1-29)NH2 or 0.1, 1, 10 or 100 nM, orexin-B individually or in combinations with 0.1 and 1000 nM GnRH or 10 and 1000 nM GRF. Secreted LH and GH were measured at 4 h after treatment. Basal LH and GH secretion (control; n = 6 pigs) was 183 +/- 18 and 108 +/- 4.8 ng/well, respectively. Relative to control at 4 h, all doses of GnRH and GRF increased (P < 0.0001) LH and GH secretion, respectively. All doses of orexin-B increased (P < 0.01) LH secretion, except for the 0.1 nM dose. Basal GH secretion was unaffected by orexin-B. Addition of 1, 10 or 100 nM orexin-B in combinations with 0.1 nM GnRH increased (P < 0.001) LH secretion compared to GnRH alone. Only 0.1 nM (P = 0.06) and 100 nM (P < 0.001) orexin-B in combinations with 1000 nM GnRH increased LH secretion compared to GnRH alone. All doses of orexin-B in combination with 1000 nM GRF suppressed (P < 0.0001) GH secretion compare to GRF alone, while only 0.1 nM orexin-B in combination with 10 nM GRF suppressed (P < 0.01) GH secretion compared to GRF. These results indicate that orexin may directly modulate LH and GH secretion at the level of the pituitary gland.     

Influence of frame size and zeranol on growth, compositional growth and plasma hormone characteristics

A 2 X 2 factorially arranged trial was conducted to compare effects of implant (zeranol) and frame size on weight and compositional gain, and plasma hormone concentrations. Angus, Charolais X Hereford and Hereford X Angus yearling steers (34 steers averaging 270 kg body weight) were randomly assigned to treatments of small (SF) vs large frame (LF) and implant (I) vs no implant (NI). Steers were implanted at 0 and 97 d and individually fed an 81% whole shelled corn and 11.5% corn silage-based diet (dry basis) for a 175-d period. Shrunk weights and body measurements for frame size determination were taken initially and at approximately 28-d intervals; blood was collected via venipuncture at 14-d intervals for analyses of insulin (IN), triiodothyronine (T3), thyroxine (T4) and glucose concentrations. Steers were also counted in a whole body counter for measurement of 40K content and prediction of whole body protein and fat. The I steers showed an improvement (P less than .05) in daily gain regardless of frame size for the total trial. The I LF steers required 18% more dry matter to attain higher daily gain for 97 to 175 d; I steers were more efficient (P less than .05) at converting dry matter to gain during 0 to 97 d and 0 to 175 d. Daily fat deposition was increased (P less than .05) in I steers, while protein deposition was not affected by I. Plasma IN concentrations were numerically elevated (P less than .10) in I steers regardless of frame size, during the initial 97 d. Implant did not influence (P greater than .10) plasma T3, T4 and glucose concentrations regardless of frame size. Steers responded differently to zeranol implant over time regarding plasma T4 concentrations (P less than .003). Steers differing in frame size responded similarly in rate of gain, in feed conversion and in patterns of plasma insulin concentrations to zeranol implants.     

三价铬对肥育猪生长激素分泌及垂体mRNA表达的影响

将96头体质量约65 kg的杜长大三元杂交猪,按体质量相近、公母各半的原则随机分成4组,每组3个重复.试验猪1组设为对照,饲喂基础饲粮,其余3组为试验组,分别饲喂在基础饲粮基础上添加来源于氯化铬、吡啶羧酸铬,纳米铬的含200 μg/kg铬试验饲粮.试验猪充分饲喂,自由饮水,试验为期40 d.饲养试验结束前1 d,从每组中选择6头猪,间隔15 min颈静脉采血1次,连续3 h,制备血清用于生长激素动态分泌模式研究.饲养试验结束后,按体质量相近原则从每组中选择8头猪进行屠宰,测定背膘厚和背最长肌面积;并各采取3头猪的脑垂体,RT-PCR法测定生长激素mRNA水平.结果表明,饲粮中添加200μg/kg三价纳米铬使肥育猪日增重提高了6.31%(P<0.05),料重比降低了4.61%(P<0.05),背膘厚降低了24.32%(P<0.05),背最长肌面积提高了20.22%(P<0.05).生长激素动态模式分析结果显示,纳米铬组试验猪生长激素总体水平、最低值、峰值和峰持续时间分别提高了42.62%(P<0.05)、87.94%(P<0.05)、26.60%(P<0.05)和17.19%(P<0.05),吡啶羧酸铬组试验猪生长激素总体水平、峰值分别提高了36.58%(P<0.05)和27.18%(P<0.05).垂体生长激素基因RT-PCR分析结果显示,纳米铬组试验猪垂体生长激素mRNA水平提高了27.63%(P<0.05).研究结果提示,三价纳米铬可提高肥育猪垂体生长激素mRNA水平,促进机体生长激素分泌,从而促进生长和改善胴体特性.     

Neuroendocrine regulation of growth hormone secretion in sheep. II. Effect of somatostatin on growth hormone and glucose levels.

The effect of intravenous (iv) and intracerebroventricular (icv) administration of somatostatin on the plasma levels of growth hormone (GH) and glucose was studied in sheep. Intravenous somatostatin decreased (P less than 0.001) circulating GH when infused at the rate of 5 micrograms/min (150 ng/kg/min) over 1 hr, but when used at 1 microgram/min there was no effect on plasma GH levels during infusion. At both doses used there was an indication of an increase in GH following the cessation of somatostatin infusion. Somatostatin given at both these doses iv had no effect on plasma glucose levels. When given icv neither 1.8 micrograms, 18 micrograms nor 180 micrograms somatostatin had any significant effect of plasma GH levels, although there was a significant (P less than 0.05) elevation in GH levels 75 min after 180 micrograms somatostatin icv. Plasma glucose levels did not increase following injection of somatostatin icv at 1.8 or 18 micrograms, but there was a clear hyperglycaemic episode following 180 micrograms icv. Despite a lack of effect of somatostatin on GH release when given icv, there was a clear elevation (P less than 0.05) in plasma GH levels immediately following icv administration of a somatostatin antiserum. These data indicate that iv administration of somatostatin at pharmacological levels can depress unstimulated GH levels in sheep while administration icv does not. Central administration of somatostatin increases plasma glucose levels only at high doses and seems unlikely to be of physiological importance in glucose homeostasis.     

The effect of zeranol and testosterone on Merino wethers exposed to highly oestrogenic subterranean clover pasture

Groups of Merino wethers treated with 2 doses of zeranol (6 mg and 12 mg), or testosterone cyclopentyl propionate (150 mg) and untreated controls were grazed at 2 sites, one an oestrogenic subterranean clover (Trifolium subterraneum) pasture and the other a low oestrogen medic (Medicago truncatula) pasture. The influence of oestrogenic subterranean clover on these treatments was assessed by measuring changes in teat length, bulbourethral gland weight and pathology, bodyweight, carcase weight, dressing percentage and greasy and clean fleece weights. Teat lengths were increased by all treatments except 6 mg of zeranol where increases were not significant, and although increased by exposure to oestrogenic pasture this effect were not additive. Bulbourethral gland weights were increased by both of the zeranol treatments and by oestrogenic pasture, and these effects appeared to be additive. Differences observed histologically indicated that testosterone protected whereas zeranol exacerbated the influence of oestrogen. The bodyweights of all treated groups were heavier than the controls, but carcase weights were not significantly different. However an effect was seen in the group given the 6 mg dose of zeranol on the low oestrogen site, where the dressing percentage was significantly lower than in the control and testosterone treated groups. Differences in greasy and clean fleece weights were not significant except that the washing yield of the testosterone-treated group was significantly lower at the low oestrogen site.     

Influence of catecholamines, prostaglandins and thyroid hormones on growth hormone secretion by chicken pituitary cells in vitro

In young chickens plasma concentrations of growth hormone (GH) are depressed by prostaglandins (PG) E1 and E2, epinephrine, norepinephrine, alpha 2 and beta agonists or thyroid hormones. A primary culture of chicken adenohypophyseal cells was used to examine the direct effects of these agents at the level of the pituitary as evaluated by GH release in the presence and absence of growth hormone releasing factor (GRF). Following collagenase dispersion and culture (preincubation, 48 hr) cells were exposed (incubation, 2 hr) to test agents, except for thyroid hormones which were added during the preincubation, and incubation period. Growth hormone release was increased (P less than .05) in the presence of PGE1 (10(-8)M by 34%; 10(-7)M by 54%), PGE2 (10(-8)M by 29%; 10(-7)M by 29%), PGF2 alpha (10(-8)M by 28%), and the beta agonist isoproterenol (10(-7)M by 46%). Basal GH release from chicken pituitary cells was not affected by dopamine, norepinephrine, epinephrine, thyroxine (T4), triiodothyronine (T3), or alpha adrenergic agonists. Growth hormone releasing factor stimulated GH release was not affected by the presence of prostaglandins E1, E2 or F2 alpha in the incubation media. However, GRF stimulated GH release was reduced by high doses of catecholamines: dopamine (10(-6)M by 34%), norepinephrine (10(-6)M by 74%), epinephrine (10(-8)M by 47%; 10(-7)M by 41%; 10(-6)M by 89%), and by the alpha 1 adrenergic agonist, phenylephrine (10(-7)M by 52%), the alpha 2 agonist, clonidine (10(-8)M by 34%; 10(-7)M by 83%) and the beta agonist, isoproterenol (10(-7)M by 64%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroendocrine regulation of growth hormone secretion in sheep. V. Growth hormone releasing factor and thyrotrophin releasing hormone.

The effects of intravenous (IV) and intracerebroventricular (ICV) administration of either bovine growth hormone releasing hormone (GRF) or thyrotrophin releasing hormone (TRH) on plasma growth hormone (GH) and glucose levels have been examined in sheep. Intravenous GRF 1-29NH2 at 3 and 30 micrograms stimulated an increase in GH levels in a dose-dependent fashion; administration of GRF into a lateral cerebral ventricle, however, produced a smaller GH response which was similar at these two doses. Evaluation of somatostatin levels in petrosal sinus blood (which collects pituitary effluent blood) showed that ICV administration of GRF stimulated a release of somatostatin into the blood. Furthermore, concurrent administration of GRF and a potent anti-somatostatin serum ICV resulted in a much enhanced release of GH which was similar to that obtained with a comparable dose of GRF given IV. TRH (as another putative GH-secretagogue) was also administered both IV and ICV. When given IV, 200 micrograms (but not 100 micrograms) TRH produced an elevation in GH levels. By contrast, when 5 micrograms TRH was given ICV there was a decrease in circulating GH levels, but no change in plasma somatostatin concentrations. These results indicate that the smaller GH response to ICV- compared with IV-administered GRF is due to the release of somatostatin within the brain. In addition, it would seem that TRH is not a physiological GH-secretagogue in sheep.     

Injection of neuropeptide Y into the third cerebroventricle differentially influences pituitary secretion of luteinizing hormone and growth hormone in ovariectomized cows.

Hypothalamic neurons that control the luteinizing hormone (LH) and growth hormone (GH) axes are localized in regions that also express neuropeptide Y (NPY). Increased hypothalamic expression of NPY due to diet restriction has been associated with suppressed secretion of LH and enhanced secretion of GH in numerous species. However, these physiological relationships have not been described in cattle. Thus, two studies were conducted to characterize these relationships using ovariectomized (Experiment 1) or ovariectomized estrogen-implanted (Experiment 2) cows. In Experiment 1, four well-nourished, ovariectomized cows received third cerebroventricular (TCV) injections of 50 and 500 micrograms of NPY in a split-plot design. Venous blood was collected at 10-min intervals from -4 hr (pre-injection control period) to +4 hr (postinjection treatment period) relative to TCV injection. NPY suppressed (P < or = 0.04) tonic secretion of LH irrespective of dose and tended to stimulate (P < or = 0.10) an increase in tonic secretion of GH. In Experiment 2, six ovariectomized cows that were well nourished and implanted with estradiol received TCV injections of 0, 50, or 500 micrograms of NPY in a replicated 3 x 3 Latin Square. Both doses of NPY suppressed (P < 0.06) mean concentration of LH relative to the 0-microgram dose. The 50-microgram dose of NPY tended (P < 0.10) to increase the amplitude of GH pulses. In conclusion, TCV injection of NPY suppressed pituitary secretion of LH and simultaneously tended to increase pituitary secretion of GH.     

Neuropeptide Y modulates growth hormone but not luteinizing hormone secretion from prepuberal gilt anterior pituitary cells in culture

Pituitary cells, from seven 160- to 170-day-old pigs, were studied in primary culture to determine the affects NPY on LH and GH secretion at the level of the pituitary. On day 4 of culture, medium was discarded, plates were rinsed twice with serum-free medium and cells were cultured in 1 ml fresh medium without serum and challenged individually with 10(-10), 10(-8) or 10(-6) M [Ala(15)]-h growth hormone-releasing factor-(1-29)NH(2) (GRF); 10(-9), 10(-8) or 10(-7) M GnRH or 10(-9), 10(-8), 10(-7) or 10(-6) M NPY individually or in combinations with 10(-9) or 10(-8) M GnRH or 10(-8) or 10(-6)M GRF. Cells were exposed to treatment for 4 h at which time medium was harvested and quantified for LH and GH. Basal LH secretion (control; n = 7 pituitaries) was 12 +/- 6 ng/well. Relative to control at 4 h, 10(-9), 10(-8) and 10(-7) M GnRH increased (P < 0.01) LH secretion by 169, 176 and 197%, respectively. Neuropeptide-Y did not alter (P > 0.4) basal LH secretion nor 10(-8) M GnRH-induced increase in LH secretion but 10(-9) M GnRH-stimulated LH secretion was reduced by NPY and was not different from control or GnRH alone. Basal GH secretion (control; n = 7 pituitaries) was 56 +/- 12 ng/well. Relative to control at 4 h, 10(-10), 10(-8) and 10(-6) M GRF increased GH secretion by 111%, 125% (P < 0.01) and 150% (P < 0.01), respectively. Only 10(-6) M (134%) and 10(-7) M (125%) NPY increased (P < 0.04) basal GH secretion. Addition of 10(-9), 10(-8) and 10(-7) M NPY in combination with 10(-8) M GRF suppressed (P < 0.04) GRF-stimulated GH secretion. However, 10(-9) M NPY enhanced (P < 0.06) the GH response to 10(-6) M GRF. These results demonstrate that NPY may directly modulate GH secretion at the level of the pituitary gland.     

Influence of zeranol and breed on growth, composition of gain, and plasma hormone concentrations

Seven Angus and six Brangus steers averaging 225 and 245 kg, respectively, were assigned randomly to zeranol (36 mg) implant (I) and no implant (NI) treatments. Steers had ad libitum access to a corn silage diet plus .68 kg of a soybean meal-based supplement fed daily. Steers were bled via jugular catheters on d 0, 28, 56, and 84 at 15-min intervals for 4 h before and 4 h after feeding. Concentrations of growth hormone (GH), insulin (INS), triiodothyronine (T3), thyroxine (T4), and glucose were determined. Whole-body protein and fat contents were monitored. A breed x I interaction (for d 56 to 84 and d 0 to 84) was observed for ADG (P less than .05 and P less than .07, respectively), feed conversion (P less than .05 and P less than .07, respectively), and protein deposition (for d 0 to 29 and d 0 to 84; P less than .07 and P less than .05, respectively). These interactions were attributed to a greater response to I by Angus than by Brangus steers. A feeding x period interaction (P less than .10) was observed for mean GH concentration, and INS, T4, and T3 concentrations were higher (P less than .05) during the 4-h postfeeding period than during the 4-h prefeeding period. The implant increased (P less than .08) mean GH concentration but did not alter the frequency, duration, or amplitude of plasma GH peaks. Steers that were implanted had lower (P less than .05) plasma T3. Brangus steers had lower (P less than .05) plasma glucose, T3, and T4 concentrations than Angus steers. Results indicate that growth factors beyond those measured are responsible for the anabolic response to zeranol.     

Adrenergic regulation of growt hormone secretion in the ewe

This study examined the role of the adrenergic system in the regulation of growth hormone (GH) secretion in sheep. Intravenous infusion of noradrenaline (0.5μg/kg per min for 2 hr) totally suppressed plasma GH concentrations. Concomitant treatment of animals with the β-adrenergic antagonist propranolol completely blocked the noradrenaline-induced suppression of GH. In contrast, intravenous injection of the centrally acting α₂-agonist clonidine (2μg/kg) elicited a release of GH. To further investigate the central adrenergic regulation of GH secretion 10 μg of noradrenaline or adrenaline was microinjected (1μl) directly into the preoptic area of the hypothalamus of ovariectomized ewes. When the time of injection coincided with a GH trough period, both noradrenaline and adrenaline caused an increase in plasma GH concentrations, whereas if the injection coincided with an endogenous pulse of GH no additional GH response was obtained. In conclusion, these results provide evidence for the involvement of the adrenergic system in the regulation of GH secretion in sheep. Centrally, adrenergic pathways exert a stimulatory effect on GH release via an α₂-adrenergic system, whereas peripherally adrenergic pathways exert an inhibitory effect via β-adrenergic mediated mechanisms. Furthermore, adrenergic stimulation of the preoptic area may inhibit somatostatin activity and directly facilitate a GH pulse. Alternatively, adrenergic innervation of the preoptic area may influence neurons (somatostatin or other) that project to the arcuate nucleus and stimulate the release of GH-releasing factor.     

Effects of zeranol on reproduction in beef bulls: luteinizing hormone, follicle-stimulating hormone, and testosterone secretion in response to gonadotropin-releasing hormone and human chorionic gonadotropin

Effects of zeranol on the maturation of the adenohypophyseal-gonadal axis were studied in beef bulls. Calves were implanted with 36 mg of zeranol at 3-month intervals from birth through 6 months of age (group 2, n = 10) or were not treated (control group 1, n = 10). After 9 months, group-2 calves were given implants of 36 mg of zeranol at 3-month intervals through 18 months of age (group 2B, n = 5) or were not reimplanted (group 2A, n = 5). Areas under the curves outlined by concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone for 6 hours after the administration of 100 micrograms of gonadotropin-releasing hormone (GnRH) were calculated. Gonadotropin-releasing hormone was administered at 3-month intervals from 1.5 through 19.5 months of age. Areas under the curves for concentrations of testosterone for 4 hours after the administration of 10,000 IU of human chorionic gonadotropin (HCG) at 4.5, 7.5, and 10.5 months or 1,000 IU at 13.5 and 16.5 months of age also were calculated. The amount of FSH released was greater (P less than 0.05) for group-2 than for group-1 calves at 4.5 and 7.5 months of age. The amount of FSH released in groups 2A and 2B tended (P less than 0.10) to be greater than that for group 1. Significant differences between groups 2A and 2B were not observed. The amount of LH released at 7.5 months of age was less for groups 1 and 2 than that at earlier ages, and the decrease was greater (P less than 0.05) for group 2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin

The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly (icv) or intravenously (iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 μg or 200 μg of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P<0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of anti-somatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 μg icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P<0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.     

猪铜蓝蛋白的分离纯化及对垂体细胞分泌生长激素的影响

采用硫酸铵分级沉淀分离,DEAE-sepharose离子交换,羟基磷灰石吸附层析,Superdex-200凝胶过滤纯化,从猪血清中分离纯化出电泳纯的一种蛋白质.进一步研究,其相对分子质量为123 500,等电点为5.08,分子含铜原子数为6个,含糖量为7.8%,亚基数为1,经分析为猪血清铜蓝蛋白.用含不同质量浓度铜蓝蛋白(0、0.1、0.2、0.4、0.8、1.2 g/L)的无血清培养液培养已培养48 h的新生仔猪脑垂体细胞12 h,于2、4、8、12 h分别收集培养液,用放免法测定培养液中GH浓度,结果表明铜蓝蛋白质量浓度为0.2、0.4、0.8、1.2 g/L组垂体细胞生长激素的分泌显著高于0 g/L组,其中以0.4 g/L组、换液培养8 h,垂体细胞生长激素分泌最为明显.     

Neuroendocrine regulation of growth hormone secretion in sheep. III. Serotoninergic systems.

The role of serotoninergic pathways in the regulation of growth hormone secretion in the sheep has been investigated. Both peripheral and central routes of administration of serotonin agonists and antagonists have been used. Intravenous administration of the serotonin agonist, buspirone, at 1.2 mg/kg/h lowered plasma GH levels (P less than 0.001) but at 0.21 mg/kg/h there was no significant decrease. Intracerebroventricular (icv) administration of serotonin itself also depressed GH levels (P less than 0.01). The serotonin antagonist, cyproheptadine, failed to affect GH concentrations when given either intravenously (0.25 mg/kg/h) or intracerebroventricularly (4 mg). Neither serotonin nor cyproheptadine had any significant effect on plasma glucose or cortisol levels when administered icv. The possible role of somatostatin in mediating the serotonin associated decrease in GH was investigated by concurrent administration of serotonin and a specific, potent anti-somatostatin serum into a cerebral ventricle. This treatment also resulted in a marked, sustained depression in GH (P less than 0.001). These data suggest that serotonin can inhibit release of GH from the pituitary in sheep and that this is independent of hypothalamic somatostatin.