Preoperative short-term administration of octreotide for facilitating transsphenoidal removal of invasive growth hormone-secreting macroadenomas.
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The somatostatin analog octreotide was administered prior to transsphenoidal surgery in three patients with tumors that extended to the suprasellar space and one side of the cavernous sinus. Octreotide, 100 micrograms twice a day, was subcutaneously injected for 2 weeks. Octreotide administration reduced the serum growth hormone (GH) levels in these patients from 82 to 22 ng/ml, from 148 to 12 ng/ml, and from 129 to 9 ng/ml. The tumor size shrank by about 50%, and the suprasellar extension disappeared in two patients. The main tumor was sharply dissected from the normal pituitary gland at surgery. Intracavernous portions were removed using a curette. Postoperatively, GH levels were less than 5 ng/ml in two patients, and 8.5 ng/ml in one patient. Follow-up magnetic resonance imaging revealed a small residual tumor in one side of the cavernous sinus in all patients. Follow-up GH levels were less than 5 ng/ml in one patient, and less than 2 ng/ml in two patients treated with bromocriptine. Preoperative administration of octreotide for 2 weeks reduced tumor volume and allowed near-total surgical resection of invasive macroadenomas without compromising the treatment course. Residual tumor due to intracavernous extension can be managed with bromocriptine or gamma knife radiosurgery. (+info)
Effects of active immunization against growth-hormone releasing factor on puberty and reproductive development in gilts.
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Hormones within the somatotropin cascade influence several physiological traits, including growth and reproduction. Active immunization against growth hormone-releasing factor (GRFi) initiated at 3 or 6 mo of age decreased weight gain, increased deposition of fat, and delayed puberty in heifers. Two experiments were conducted to investigate the effects of GRFi on puberty and subsequent ovulation rate in gilts. Crossbred gilts were actively immunized against GRF-(1-29)-(Gly)2-Cys-NH2 conjugated to human serum albumin (GRFi) or against human serum albumin alone (HSAi). In Exp. 1, gilts were immunized against GRF (n = 12) or HSA (n = 12) at 92 +/- 1 d of age. At 191 d of age, antibody titers against GRF were greater (P < .05) in GRFi (55.5 +/- 1.3%) than in HSAi (.4 +/- 2%) gilts. The GRFi decreased (P < .05) BW (86 +/- 3 vs 104 +/- 3 kg) by 181 d of age and increased (P < .05) backfat depth (15.7 +/- .4 vs 14.8 +/- .4 mm) by 130 d of age. At 181 d of age, GRFi reduced the frequency of ST release (1.0 +/- .5 vs 5.0 +/- .5, peaks/24 h; P < .0001) and decreased (P < .01) ST (1.1 +/- .06 vs 1.7 +/- .06 ng/mL), IGF-I (29 +/- 2 vs 107 +/- 2 ng/mL), and insulin concentrations (3.5 +/- .2 vs 6.3 +/- .2 ng/mL). The GRFi decreased (P < .05) feed conversion efficiency but did not alter age at puberty (GRFi = 199 +/- 5 d vs HSAi = 202 +/- 5 d) or ovulation rate after second estrus (GRFi = 10.7 +/- .4 vs HSAi = 11.8 +/- .5). In Exp. 2, gilts were immunized against GRF (n = 35) or HSA (n = 35) at 35 +/- 1 d of age. The GRFi at 35 d of age did not alter the number of surface follicles or uterine weight between 93 and 102 d of age, but GRFi decreased (P < .05) ovarian weight (.41 +/- .08 vs 1.58 +/- .4 g) and uterine length (17.2 +/- 1.1 vs 25.3 +/- 2.3 cm). Immunization against GRF reduced (P < .05) serum IGF-I (GRFi = 50 +/- 4 vs HSAi = 137 +/- 4 ng/mL) and BW (GRFi = 71 +/- 3 vs HSAi = 105 +/- 3 kg) and increased (P < .05) backfat depth (GRFi = .38 +/- .03 vs HSAi = .25 +/- .02 mm/kg). Age at puberty was similar in GRFi and HSAi gilts, but ovulation rate was lower (P < .05) after third estrus in GRFi (11.3 +/- .8) than in HSAi (13.8 +/- .8) gilts. Thus, GRFi at 92 or 35 d of age decreased serum ST, IGF-I, and BW in prepubertal gilts without altering age of puberty. However, GRFi at 35 d of age, but not 92 d of age, decreased ovulation rate. These results indicate that alterations in the somatotropic axis at 1 mo of age can influence reproductive development in pubertal gilts. (+info)
Effects of recombinant equine somatotropin on wound healing, carbohydrate and lipid metabolism, and endogenous somatotropin responses to secretagogues in geldings.
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The primary purpose of this experiment was to assess the possible beneficial effects of recombinant equine somatotropin (reST) administration on wound healing in adult geldings. The effects of the 21-d reST treatment on carbohydrate and lipid metabolism and on endogenous ST characteristics were monitored as well. Single, full-thickness skin incisions (7.62 x 7.62 cm) were made in the pectoral region of all geldings on d 0. Treated geldings received reST at 20 microg/kg BW i.m., and control geldings received vehicle (10 mM sodium borate) at equivalent volumes daily from d 0 (immediately after surgery) through d 20. Tracings of the wounds were made with acetate transparencies, and wound areas were calculated via a digital analyzer. In addition to once-daily blood samples collected at specified days throughout the treatment period, an i.v. glucose tolerance test was performed on d 16, and three assessments of endogenous ST secretion were performed in the 2 d immediately following the end of treatment: epinephrine administration during the morning of d 21, an exercise test during the afternoon of d 21, and i.v. aspartic acid infusion on d 22. There was no effect (P > . 1) of reST treatment on wound healing as assessed by changes in wound areas. Daily plasma ST, IGF-I, glucose, and insulin concentrations were higher (P < .05) and urea-nitrogen concentrations were lower (P < .001) in geldings receiving reST relative to controls. Glucose, NEFA, and insulin concentrations were all higher (P < .01) in reST-treated geldings before glucose infusion on d 16, and the responses to glucose were greater (P < .05) as well. Epinephrine administration increased (P < .02) ST concentrations in control geldings on d 21 but not in reST-treated geldings; a similar suppressive effect of reST treatment was observed for the ST response to exercise (P < .001). After aspartic acid infusion on d 22, reST-treated geldings had a much smaller (P < .001) ST response than did control geldings. In conclusion, reST administered to geldings at 20 microg/kg BW i.m. caused hyperglycemia, hyperinsulinemia, insulin insensitivity, mobilization of fatty acids, and an apparent negative feedback on the pituitary's ST response to various stimuli known to induce ST secretion. However, there was no beneficial effect of reST treatment with the wound model used in this experiment. (+info)
Abnormal growth hormone responses to CB-154 and thyrotropin-releasing hormone (TRH) in patients with acromegaly.
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CB-154 (2-Br-alpha-ergocriptine) stimulates growth hormone (GH) release in normal subjects. In acromegaly, however, this agent often decreases plasma GH level paradoxically. In order to examine the mechanism of the so-called "paradoxical decrease" in plasma GH with CB-154, GH responses to CB-154 were compared with GH responses to thyrotropin-releasing hormone (TRH), arginine, and luteinizing hormone-releasing hormone (LH-RH) in 20 cases of acromegaly. CB-154, as well as L-dopa, elicited decrease in GH in those patients whose GH secretion was more responsive to TRH and less responsive to arginine. These results suggest that, like L-dopa, CB-154 has similar dual actions of TRH antagonistic GH decrease and GH-RF (GH-releasing factor) facilitative GH increase. Moreover, it was speculated from this study that CB-154 has no significant effect on LH-RH release. The value of (increase ratio of GH on TRH)/(increase ratio of GH on arginine) can be used as an index for the indication of chronic CB-154 therapy in patients with acromegaly. (+info)
Insulin hypoglycemia and growth hormone secretion in sheep: a paradox revisited.
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Although insulin-induced hypoglycemia is a potent stimulus for growth hormone (GH) secretion in humans, hypoglycemia was reported to suppress GH in sheep. We investigated whether GH suppression in sheep during insulin hypoglycemia resulted from the dose of insulin administered or the fed state of the animal. Saline or insulin (0.05, 0.2, 1.0, or 5.0 U/kg) intravenous boluses were administered to eight fasted ewes in a crossover experiment. In another experiment, four sheep were fed 2 h before intravenous administrations of either 0.2 or 5 U/kg of insulin. All doses of insulin resulted in comparable hypoglycemia, although the duration of hypoglycemia increased directly with insulin dose. Hypoglycemia in fasted animals stimulated GH secretion. The GH rise above baseline was inversely related to the insulin dose, and the insulin doses of 1 and 5 U/kg resulted in late suppression of GH below baseline concentrations. Insulin administration to fed animals caused an identical degree of hypoglycemia but no increase in GH. Insulin-hypoglycemia stimulates GH secretion in sheep in a manner similar to humans, and the response is dependent on both fed state and insulin dose. (+info)
Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis.
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This time-course study further explored the mechanisms whereby monoclonal antibodies (MAbs) may enhance growth hormone (GH) effects. Hypophysectomized rats were killed 0, 1, 3, 6, 12, 24, and 48 h after a single injection of bovine (b) GH alone or complexed with an anti-bGH MAb. Serum insulin-like growth factor I (IGF-I) concentrations were increased more and for a longer period after MAb-GH complexes (peak at 24 h: 295 +/- 24 ng/ml) than after bGH alone (peak at 12 h: 219 +/- 37 ng/ml; P < 0.01), whereas liver IGF-I mRNA was similar at 12 h in both groups but remained higher at 24 h (by 65%, P < 0.001) and 48 h (by 64%, P < 0.001) in the presence of the MAb. Induction of serum insulin-like growth factor-binding protein (IGFBP)-3 and liver IGFBP-3 mRNA by bGH also was markedly amplified by the MAb (3.6- and 2-fold at 24 h, respectively; P < 0.01). GH receptors (GHR) remained occupied for a longer period after MAb-GH injection (36 +/- 16 and 35 +/- 8% at 6 and 12 h, respectively) compared with bGH alone (0 +/- 28 and -15 +/- 11%), whereas total liver GH-binding sites and GHR mRNA levels were not affected by the MAb. We conclude that MAbs against GH amplify and prolong the serum IGF-I response to GH, which may result from both a prolongation of liver IGF-I synthesis and an enhanced induction of IGFBP-3. These two effects may in turn be the consequences of sustained GH binding to its liver receptors in the presence of MAb. (+info)
Effects of oral chlortetracycline and dietary protein level on plasma concentrations of growth hormone and thyroid hormones in beef steers before and after challenge with a combination of thyrotropin-releasing hormone and growth hormone-releasing hormone.
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The objective of this study was to determine the effect of a subtherapeutic level of chlortetracycline (CTC) fed to growing beef steers under conditions of limited and adequate dietary protein on plasma concentrations of GH, thyroid-stimulating hormone (TSH), and thyroid hormones before and after an injection of thyrotropin-releasing hormone (TRH) + GHRH. Young beef steers (n = 32; average BW = 285 kg) were assigned to a 2x2 factorial arrangement of treatments of either a 10 or 13% crude protein diet (70% concentrate, 15% wheat straw, and 15% cottonseed hulls) and either a corn meal carrier or carrier + 350 mg of CTC daily top dressed on the diet. Steers were fed ad libitum amounts of diet for 56 d, and a jugular catheter was then placed in each steer in four groups (two steers from each treatment combination per group) during four consecutive days (one group per day). Each steer was injected via the jugular catheter with 1.0 microg/kg BW TRH + .1 microg/kg BW GHRH in 10 mL of saline at 0800. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 120, 240, and 360 min after releasing hormone injection. Plasma samples were analyzed for GH, TSH, thyroxine (T4), and triiodothyronine (T3). After 84 d on trial, the steers were slaughtered and the pituitary and samples of liver were collected and analyzed for 5'-deiodinase activity. Feeding CTC attenuated the GH response to releasing hormone challenge by 26% for both area under the response curve (P<.03) and peak response (P<.10). Likewise, CTC attenuated the TSH response to releasing hormone challenge for area under the response curve by 16% (P<.10) and peak response by 33% (P<.02), and attenuated the T4 response for area under the curve by 12% (P<.08) and peak response by 14% (P<.04). Type II deiodinase activity in the pituitary was 36% less (P<.02) in CTC-fed steers than in steers not fed CTC. The results of this study are interpreted to suggest that feeding subtherapeutic levels of CTC to young growing beef cattle attenuates the release of GH and TSH in response to pituitary releasing hormones, suggesting a mechanism by which CTC may influence tissue deposition in cattle. (+info)
Effects of porcine sometotropin on calcium and phosphorus balance and markers of bone metabolism in finishing pigs.
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Six sets of four littermate barrows initially averaging 75.5 kg BW were equally fed (within blocks) fortified corn-soybean meal diets (1.30% lysine) containing two concentrations of Ca (.50 and 1.00%) and P (.45% and .90%) in a 34-d test. One-half of the pigs were injected with 4 mg of porcine ST (pST)/d. Following a 7-d adjustment period, total collection of feces and urine was performed during two periods (d 1 to 10 and d 20 to 30) for the determination of Ca and P apparent digestibility (absorption) and retention. Pigs were bled after each period (d 10, 20, and 30) for the determination of serum metabolites associated with Ca, P, and bone metabolism. Feed intake for the 30-d period averaged 2,020 g/d. There were no treatment x period interactions, so the absorption and retention data were pooled across periods. The absorption and retention of Ca and P were greater (P<.01) in pigs fed the higher Ca and P levels. Within each Ca and P level, pST reduced (P<.01) fecal Ca and P excretion. Administration of pST did not affect urinary P excretion, but it increased (P<.03) urinary Ca excretion in pigs fed the low-Ca diet. The absorption and retention of Ca and P were increased (P<.01) by pST; however, the increases in Ca retention and P absorption and retention on an absolute basis (g/d) were more pronounced in pST-treated pigs consuming the higher Ca and P diet (interaction, P<.10). Serum concentrations of 1,25-dihydroxyvitamin D3, osteocalcin, and IGF-I on d 10 and 30 were increased (P<.07) with pST administration. However, the increases in 1,25-dihydroxyvitamin D3 and osteocalcin in pST-treated pigs were more pronounced when the lower dietary Ca and P levels were fed (interaction, P<.08). Urinary excretion of hydroxyproline increased (P<.01) with pST administration, but this effect was more pronounced in pST-treated pigs fed the lower Ca and P diet (interaction, P<.09). These results suggest that pST increases the absorption and retention of Ca and P independent of dietary Ca and P level. However, serum measures associated with Ca, P, and bone metabolism in pST-treated pigs were dependent on the Ca and P content of the diet, suggesting an effect of pST on the homeostatic control of Ca, P, and bone metabolism. (+info)