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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Use of reverse hemolytic plaque assays revealed that, as in the rat, bovine somatotropes are functionally heterogeneous with respect to regulated GH release. Uniquely, this heterogeneity is manifested by the appearance of a distinct subpopulation of GH cells that release hormone only in the presence of the hypothalamic secretagogues GRF and/or TRH. Although these cells did not release GH in the absence of stimulatory agents, immunocytochemical detection of GH demonstrated these cells were capable of hormone storage. The relative abundance of silent somatotropes varied according to the hypothalamic secretagogue applied to the culture (GRF and/or TRH) and the physiologic state of the tissue donor. In cell cultures obtained from castrated males, 4.2 +/- 1.2%, 3.0 +/- 0.7%, and 6.8 +/- 1.2% (mean +/- SEM; n = 14) of all pituitary cells were induced to release detectable amounts of GH by GRF, TRH, and GRF/TRH, respectively. When pituitary cells obtained from gonad-intact males (n = 4) and females (n = 4) were tested, only incubation with GRF (14.1 +/- 2.5%; 6.9 +/- 2.3%, respectively) and GRF/TRH (15.2 +/- 2.4%; 9.2 +/- 2.6%, respectively) stimulated a significant population of these silent cells. A combined analysis of the proportion of GH secretors and the relative amount of hormone released per cell revealed that a substantial fraction of the GH secreted in vitro after stimulation is attributable to the recruitment of silent somatotropes into the secretory pool. Taken together, these results reveal the existence of a unique form of GH cell heterogeneity--the silent somatotrope. Moreover, our findings demonstrate that this somatotrope population could provide a cellular basis for the readily releasable pool of GH in the bovine pituitary.
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PMID:Bovine pituitary cells exhibit a unique form of somatotrope secretory heterogeneity. 212 61

In an attempt to clarify the regulatory role in GH secretion of central alpha-adrenergic and dopaminergic mechanisms, the effects of iv administration of alpha 1- and alpha 2-adrenergic antagonists and dopaminergic antagonists were investigated in undisturbed conscious male rabbits. During a 6-h observation period (1030-1630 h), control animals demonstrated spontaneous pulsatile GH secretion with mean (+/- SEM) 6-h GH levels of 6.49 +/- 0.54 ng/ml (n = 16). Intravenous injection of yohimbine (YOM; an alpha 2-antagonist), chlorpromazine (CPZ), and haloperidol (HAL; dopamine and alpha-adrenergic antagonists) completely suppressed this pulsatile GH secretion (mean 6-h GH levels, 2.98 +/- 0.24, 3.48 +/- 0.24, and 2.91 +/- 0.29 ng/ml, respectively; P less than 0.001), whereas prazosin (an alpha 1-antagonist), pimozide (a selective dopamine antagonist), sulpiride, and YM-09151-2 (YM; D2-specific antagonists) failed to affect the GH secretory pattern (mean 6-h GH levels, 6.61 +/- 0.73, 6.71 +/- 0.56, 5.44 +/- 0.44, and 6.87 +/- 1.44 ng/ml, respectively). While an iv injection of 2 micrograms synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) induced GH rises in prazosin-, HAL-, pimozide-, sulpiride-, and YM-treated rabbits as well as control rabbits, YOM and CPZ completely abolished these GH responses to hGRF injection. An iv injection of 10 ml antisomatostatin gamma-globulin caused a prompt and transient GH rise, followed by a sustained elevation of GH trough levels in normal control rabbits. YOM treatment completely abolished this highly oscillated GH release. However, suppression by YOM or CPZ of hGRF-induced GH rises was significantly reversed by iv administration of 10 ml antisomatostatin gamma-globulin. Therefore, the inhibitory effect of YOM and CPZ on both episodic GH release and hGRF-induced GH rises is due to the enhanced release of somatostatin, with a simultaneous suppression of endogenous GRF. On the other hand, HAL, possessing a weaker alpha-blocking action than CPZ, blunted pulsatile GH secretion, but only modestly suppressed hGRF-induced GH rises. These results suggest the following. 1) Central alpha 2-adrenergic mechanisms play a more important role in the regulation of GH secretion than alpha 1-adrenergic mechanisms in the rabbit as well as in other species. 2) The alpha 2-adrenergic blockade causes suppression of the release of hypothalamic GRF and enhanced release of endogenous somatostatin, thereby suppressing GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. 247 28

We previously reported that systemic administration of the recently described GRF peptide antagonist (N-Ac-Tyr1,D-Arg2)GRF-(1-29)-NH2 to adult male rats would suppress the pulsatile release of GH. In the present study, we have sought to determine whether this same antagonist would be efficacious in immature male rats to block spontaneous GH secretion and, as a result, retard several parameters of somatic growth. Indwelling Silastic catheters were placed into the jugular veins of immature male rats (120-140 g) at 29 days of age. After a recovery period of 48 h, beginning at 1000 h, 100-400 micrograms/kg GRF antagonist or its vehicle (controls) were injected iv immediately after withdrawing an initial blood sample from conscious undisturbed animals. Subsequent samples were obtained every 20 min until 1520 h. Red blood cells were resuspended in a restorative volume of saline and reinjected after each blood sample. Results showed that both doses of antagonist prevented the two major periods of episodic GH release observed in controls. For example, mean plasma GH (+/- SEM; nanograms per ml) at 1120 h was 9.0 +/- 2.7 in antagonist-treated rats and 37.1 +/- 5.1 in controls (P less than 0.05). Mean plasma GH (+/- SEM) at 1340 h was 10.8 +/- 3.7 in antagonist-treated rats and 38.8 +/- 9.6 in controls (P less than 0.05). Injection of 400 micrograms/kg of the structurally related VIP antagonist (N-Ac-Tyr1,D-Phe2)GRF-(1-29)-NH2, iv failed to suppress spontaneous GH release. GRF antagonist (100 micrograms/kg) was next administered twice daily iv for 4 days to 31-day-old rats in metabolic cages. This treatment essentially arrested the normal rapid body weight gain, significantly suppressed increases in body and tail lengths, and reduced increases in heart and kidney weights (P less than 0.01). Food intake and fecal output were unchanged by antagonist treatment and, therefore, did not contribute to the observed effects. These results support the idea that a number of tissues and organs are stimulated by the pulsatile secretion of GH and that a peptidic GRF receptor antagonist is useful in blocking episodic GH release in immature animals. As a consequence, this specific antagonist is effective in suppressing numerous aspects of somatic growth.
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PMID:Inhibition of pulsatile growth hormone (GH) secretion and somatic growth in immature rats with a synthetic GH-releasing factor antagonist. 249 21

We postulated that an increase in the biological effectiveness of somatostatin (SRIF) accounts, at least in part, for the decrease in basal and GRF-induced ovine GH (oGH) secretion observed around birth in the ovine fetus and neonate. To test this hypothesis, SRIF (SRIF-14; given as 30 micrograms/kg iv bolus, followed by 2 micrograms/kg.min for 75 min) was infused into chronically catheterized fetal and neonatal lambs, and the oGH response induced by GRF [GRF-(1-44) amide; 1 microgram/kg] in the presence of exogenous SRIF was compared to the oGH response induced by GRF in saline-infused controls. In fetuses of 115-122 days gestation, SRIF had no detectable effect on the oGH response to GRF [peak incremental oGH response (mean +/- SEM), 527 +/- 124 vs. 562 +/- 103 ng/ml in controls]. In neonatal lambs (3-17 days old), SRIF completely suppressed the immediate oGH response to GRF (peak incremental response, 0.8 +/- 1.3 vs. 111 +/- 34 ng/ml in controls; P less than 0.02). In late gestational fetuses (126-139 days old), a transitional pattern was observed (peak incremental oGH response, 207 +/- 56 vs. 324 +/- 30 ng/ml in controls; P less than 0.04). In the second part of this study, we explored, in the neonatal lamb, the hypothesis that SRIF withdrawal plays a role in pulsatile GH secretion and that the amount of GRF to which the somatotrope is exposed before SRIF withdrawal is a major factor in determining the amplitude of GH bursts. SRIF (SRIF-14; a 30 micrograms/kg bolus, followed by 2 micrograms/kg.min) was infused iv for 40 min, GRF [GRF-(1-44) amide; 1 microgram/kg] was injected iv 20 min after starting the SRIF infusion, and the oGH rise after SRIF withdrawal was evaluated. In one series of controls GRF was replaced by saline, and in the other SRIF was replaced by saline. The oGH rise during recovery after SRIF alone was lower than that after the combined administration of SRIF and GRF (peak oGH increment, 8 +/- 3 vs. 38 +/- 12 ng/ml; P less than 0.04). The amplitude of the GH pulse after SRIF and GRF was similar to the immediate oGH response to GRF alone. These studies show that SRIF is unable to suppress the immediate oGH response to GRF in the ovine fetus, and that the suppressive effect of SRIF on the immediate oGH response to GRF increases gradually in late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone ontogeny in the ovine fetus and neonate. XXII. The effect of somatostatin on the growth hormone (GH) response to GH-releasing factor. 256 81

The aims of this study were: (1) to test the possibility that pre-GHRH plasma GH values could reflect the functional status of the hypothalamic-somatotroph rhythm (HSR) at testing, and thus explain if it is responsible for the marked variability in GH responsiveness to GHRH challenge and (2) to see if exogenous somatostatin (SS) could disrupt this endogenous HSR and thus make the GH responses homogeneous. (1) Two to 14 GHRH acute tests (GRF-29, 1 micrograms/kg, i.v. bolus) were performed in 12 normal men and 10 normal women at the same time (0830 h) at random intervals (2 to 60 days). Blood samples to measure plasma GH were drawn at 15 min intervals before and after GHRH challenge. Given that the increments in pre-GHRH plasma GH values (I = value at 0 min minus value at -15 min) were highly correlated with either GHRH-elicited peaks of GH (men, r = 0.81; women; r = 0.69; P less than 0.0001) or the rise in GH after the challenge (r = 0.685; P less than 0.0001, in the total of tests performed), three theoretical HSR phases were proposed: (A) I greater than or equal to 0.4 microgram/l Secretory Phase; (B) I less than or equal to 0, (from GH at -15 min greater than or equal to 1.5 microgram/l), Secretion Plateau; (C) I less than or equal to 0, (from GH at -15 min less than or equal to 1.5 microgram/l), Refractory Phase. Individually, 91% of the men and 86% of the women showed a constant HSR phase when tested at the same time of day independently of the intervals between tests. GH responses (peaks, mean +/- SEM, g/l) in Phase A (women, 51.5 +/- 4.1; men, 31.4 +/- 3.2) were significantly higher (P less than 0.01) than those in Phase B (women, 22.6 +/- 1.8; men, 19.7 +/- 1.5), and these than those in Phase C (women, 9.2 +/- 1.5; men, 6.2 +/- 0.5). The great dispersion observed when GH peaks were analysed as a whole disappeared (except in Phase A in women) when they were evaluated according to the HSR Phase at testing. (2) In seven men and eight women 7 min after stopping an infusion of SS (250 micrograms/h for 3 h) a new GHRH test was performed. Plasma GH variations prior to SS infusion expressed the previous HSR Phase, while the GHRH-elicited peak of GH established the Phase at the moment of testing.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reasons for the variability in growth hormone (GH) responses to GHRH challenge: the endogenous hypothalamic-somatotroph rhythm (HSR). 257 45

The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly.
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PMID:Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly. 288 93

In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 +/- 5 ng/ml, mean +/- SEM) than in the control group (362 +/- 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 +/- 153 ng/ml) than in the control group (268 +/- 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 +/- 0.06 microgram/2 pituitaries X 2 min) was lower than that from cells of control rats (1.60 +/- 0.18 micrograms/2 pituitaries X 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10(-9) M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pituitary level.
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PMID:Growth hormone responsiveness in vivo and in vitro to growth hormone releasing factor in the spontaneously diabetic BB Wistar rat. 288 37

The effects of the diabetic state on the somatotroph's responsiveness to the secretagogues GRF and (Bu)2-cAMP and to the inhibitor somatostatin (SRIF) were evaluated in enzymatically dissociated rat adenohypophyseal cells in primary monolayer culture. Primary cultures were prepared from pituitary tissue of spontaneously diabetic BB/W rats 23-51 days after the onset of hyperglycemia and glycosuria and of age-matched diabetes-resistant control rats. Dose-related stimulation of GH release by GRF and (Bu)2cAMP did not differ significantly in the two preparations. There was no evidence of abnormal sensitivity to TRH in cultured somatotrophs of diabetic rats. Dose-related suppression of (Bu)2cAMP (0.5 mM)-stimulated GH release by 0.01-10 nM SRIF, on the other hand, was significantly affected by diabetes, as indicated by a parallel shift of the dose-response curve to the right and an increase in the IC50 value from 76 +/- 2 to 204 +/- 5 pM (mean +/- SEM; n = 3; P less than 0.001). Maximal suppression by 10 nM SRIF was identical in the two preparations. The degree to which the cultured cells' responsiveness to SRIF was reduced was unrelated to the duration and severity of the diabetic state. Hypothalamic SRIF content did not differ significantly between diabetic and diabetes-resistant rats (186 +/- 12 vs. 178 +/- 10 ng/mg protein). Nevertheless, the SRIF concentration may be elevated in hypophysealportal blood of diabetic rats; we, therefore, examined the effect of prolonged exposure of the cell cultures to SRIF or SMS 201-995 on the subsequent suppression of (Bu)2cAMP-stimulated GH release by SRIF. Addition of either SRIF (10 nM) or SMS 201-995 (5.5 nM) to the culture medium for 4 days significantly increased the IC50 values for SRIF to values similar to those obtained in cultured cells of diabetic rats. We conclude that the somatotrophs of diabetic rats are relatively resistant to SRIF. Since prolonged exposure to SRIF in vitro produced similar resistance, the desensitization in diabetic rats may be due to elevated concentrations of SRIF in hypophyseal-portal blood. This impaired responsiveness to SRIF may contribute to aberrant GH secretion in diabetes.
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PMID:Impaired suppression of growth hormone release by somatostatin in cultured adenohypophyseal cells of spontaneously diabetic BB/W rats. 290 49

The time course, concentration dependence, and mechanism of rat anterior pituitary desensitization to GRF were studied. Chronic stimulation of cultures of rat anterior pituitary cells with rat GRF (rGRF) resulted in desensitization to a subsequent challenge with the peptide. Despite a slight enhancement of GH synthesis, prolonged exposure to GRF caused substantial depletion of cellular GH pools. As a result, acute secretory responses were markedly blunted. Depletion was accompanied by a time-dependent decrease in sensitivity to rGRF; GRF EC50 values for GH release of 0.5 nM rGRF-pretreated cells were 24.8 +/- 6 (+/- SEM) pM after 2 h, 46.2 +/- 2.4 pM after 4 h, and 154.7 +/- 31 pM after 8 h compared to 9.2 +/- 0.6 pM for control cells. The process of desensitization was complete within 8 h, as cells pretreated for 24 h exhibited sensitivity to rGRF comparable to that of cells pretreated for 8 h. Desensitization was associated with a time-dependent decrease in rat anterior pituitary cell GRF-binding capacity; a 48% loss of binding sites was evident after a 2-h pretreatment with 0.5 nM rGRF, with a maximum loss occurring after 8 h. The dose of rGRF required to produce an attenuation of responsiveness did not completely correlate with the dose requirement for down-regulation of binding sites. The decrease in GRF-binding sites was not associated with any alteration of apparent Kd values, which were 0.36 (0.18-0.72) nM in control and 0.1 (0.01-0.82) nM after 8 h of exposure to 0.5 nM rGRF. Both the reduction in GRF-binding capacity and decreased sensitivity to GRF were reversible after 24 h, although cellular GH pools were not restored to control levels. These results suggest that rat anterior pituitary cells become desensitized to rGRF after chronic stimulation with a maximal concentration of the peptide. One mechanism for this decrease in apparent sensitivity to rGRF may be the pronounced reduction or down-regulation of GRF-binding sites.
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PMID:Desensitization to growth hormone-releasing factor (GRF) is associated with down-regulation of GRF-binding sites. 300 46

Three experiments were conducted to determine serum growth hormone (GH) response of bull calves (N = 4; 83 kg body wt) to iv injections and infusions of human pancreatic GH-releasing factor 1-40-OH (hpGRF). Peak GH responses to 0, 2.5, 10, and 40 micrograms hpGRF/100 kg body wt were 7 +/- 3, 8 +/- 3, 18 +/- 7, and 107 +/- 55 (mean peak height +/- SEM) ng/ml serum, respectively. Only the response to the 40-microgram dose was greater (P less than 0.05) than the 0-microgram dose. Concentrations of prolactin in serum were not affected by hpGRF treatment. In calves injected with hpGRF (20 micrograms/100 kg body wt) at 6-hr intervals for 48 hr, GH increased from a mean preinjection value of 3.1 ng/ml serum to a mean peak response value of 70 ng/ml serum. Differences in peak GH response between times of injection existed within individual calves (e.g., 10.5 ng/ml vs 184.5 ng/ml serum). Concentrations of GH in calves infused continuously with either 0 or 200 micrograms hpGRF/hr for 6 hr averaged 7.4 +/- 3 and 36.5 +/- 11 ng/ml serum, respectively (P less than 0.05). Concentrations of GH oscillated markedly in hpGRF-infused calves, but oscillations were asynchronous among calves. We conclude that GH response of bull calves to hpGRF is dose dependent and that repeated injections or continuous infusions of hpGRF elicit GH release, although magnitude of response varies considerably. We hypothesize that differences in GH response to hpGRF within and among calves, and pulsatile secretion in the face of hpGRF infusion may be related to the degree of synchrony among exogenous hpGRF and endogenous GRF and somatostatin.
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PMID:Growth hormone response of bull calves to growth hormone-releasing factor. 310 19


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