Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows
Abstract:Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1-29)-NH 2 ] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, mUltiparous Hereford cows were immunized against 2 mg GRF(l-29)-(GlY)4-Cys-NH2 conjugated to human serum albumin (GRFi, n=3) or 2 mg human serum albumin (HSAi, n=3) at 52 ± 1 d prior to parturition. Boosters (1 mg) were administered on days 12,40 and 114 postpa… Show more
“…Immunoneutralization of GRF abolishes episodic release of ST and suppresses serum ST and IGF-I in cyclic gilts [38], lactating sows [39], lactating cows [27], growing steers [2,40], and heifers [3]. Administration of booster immunizations to GRFi cows maintained suppressed serum ST and IGF-I throughout the experiment ( Fig.…”
Section: Discussionmentioning
confidence: 73%
“…Cyclic nulliparous and primiparous Angus and Charolais (n = 43) [3,26] or multiparous Angus and Hereford (n = 12) females [27], previously immunized against GRF or human serum albumin, were used. The 2-to 3-yr-old Angus and Charolais cows weighed 407 ± 11 and 440 ± 14 kg, respectively.…”
Section: Methodsmentioning
confidence: 99%
“…The multiparous Angus and Hereford cows were 5-6 yr of age and weighed 475 + 31 kg. Cows were immunized with 1.5 mg GRF-(1-29)-Gly-Gly-Cys-NH 2 conjugated to 1.5 mg human serum albumin (GRFi; Hoffmann La-Roche, Inc., Nutley, NJ) or with 1.5 mg human serum albumin (HSAi; Sigma Chemical Co., St. Louis, MO) at 6 mo of age [3,26] or at 3-4 yr of age [27]. Cows were administered booster immunizations as previously described [3,26,27]; however, the most recent booster immunization would have been given at least 3 mo before initiation of this study.…”
We investigated the effect of administration of somatotropin (ST) and/or eCG on insulin-like growth factor I (IGF-I) and IGF-binding proteins (IGFBP) in serum and follicular fluid (FFL) of cattle actively immunized against growth hormone-releasing factor (GRF). Cyclic beef cattle, previously immunized against GRF-(1-29)-Gly-Gly-Cys-NH2 conjugated to human serum albumin (synthesized and provided by Hoffmann-LaRoche, Inc., Nutley, NJ; GRFi, n = 31) or to human serum albumin alone (HSAi, n = 26), received (i.m.): 1) 25 mg recombinantly derived methionyl somatotropin (rbST, n = 14; sometribove provided by Monsanto Co., St. Louis, MO); 2) 1100 IU eCG (n = 10); 3) rbST and eCG (rbST-eCG, n = 15); or 4) vehicle (VEH, n = 17) at 0 and 24 h after receiving prostaglandin F2 alpha (PGF2 alpha). Serum samples were collected at 0 and 40 h after PGF2 alpha, and the ovary bearing the largest follicle (DOM) was removed 44.0 +/- 0.5 h after PGF2 alpha; FFL was harvested from DOM and the subordinate follicle (SUB). Before treatment (0 h), GRFi cows had lower serum ST (0.6 +/- 0.2 vs. 2.2 +/- 0.2 ng/ml; p < 0.01) and IGF-I (26 +/- 4 vs. 72 +/- 4 ng/ml; p < 0.01), but greater IGFBP-2 (594 +/- 48 vs. 384 +/- 52 ng/ml; p < 0.01) than HSAi cows. Serum and FFL concentrations of IGF-I or IGFBP-2 were not different between rbST- and rbST-eCG-treated cows or between VEH- and eCG-treated cows at Hour 40 after the initial treatment injection; therefore, data were combined and designated as rbST and VEH, respectively. Serum IGF-I was increased to a greater extent (percentage increase above 0 h) by rbST treatment in GRFi (362 +/- 24) than in HSAi (176 +/- 16) cows (immunization by treatment, p < 0.01). Across GRFi and HSAi, rbST lowered serum IGFBP-2 (342 +/- 31 vs. 541 +/- 27 ng/ml, rbST vs. VEH; p < 0.01). Diameters of DOM or SUB were not affected by immunization or treatment. Concentrations of IGF-I and IGFBP-3 (determined by ligand blot analysis) in FFL from both DOM and SUB were lower (p < 0.05) in GRFi than in HSAi cows. In contrast, IGFBP-2 in FFL was elevated in SUB, but not DOM, in GRFi compared to HSAi cows.(ABSTRACT TRUNCATED AT 400 WORDS)
“…Immunoneutralization of GRF abolishes episodic release of ST and suppresses serum ST and IGF-I in cyclic gilts [38], lactating sows [39], lactating cows [27], growing steers [2,40], and heifers [3]. Administration of booster immunizations to GRFi cows maintained suppressed serum ST and IGF-I throughout the experiment ( Fig.…”
Section: Discussionmentioning
confidence: 73%
“…Cyclic nulliparous and primiparous Angus and Charolais (n = 43) [3,26] or multiparous Angus and Hereford (n = 12) females [27], previously immunized against GRF or human serum albumin, were used. The 2-to 3-yr-old Angus and Charolais cows weighed 407 ± 11 and 440 ± 14 kg, respectively.…”
Section: Methodsmentioning
confidence: 99%
“…The multiparous Angus and Hereford cows were 5-6 yr of age and weighed 475 + 31 kg. Cows were immunized with 1.5 mg GRF-(1-29)-Gly-Gly-Cys-NH 2 conjugated to 1.5 mg human serum albumin (GRFi; Hoffmann La-Roche, Inc., Nutley, NJ) or with 1.5 mg human serum albumin (HSAi; Sigma Chemical Co., St. Louis, MO) at 6 mo of age [3,26] or at 3-4 yr of age [27]. Cows were administered booster immunizations as previously described [3,26,27]; however, the most recent booster immunization would have been given at least 3 mo before initiation of this study.…”
We investigated the effect of administration of somatotropin (ST) and/or eCG on insulin-like growth factor I (IGF-I) and IGF-binding proteins (IGFBP) in serum and follicular fluid (FFL) of cattle actively immunized against growth hormone-releasing factor (GRF). Cyclic beef cattle, previously immunized against GRF-(1-29)-Gly-Gly-Cys-NH2 conjugated to human serum albumin (synthesized and provided by Hoffmann-LaRoche, Inc., Nutley, NJ; GRFi, n = 31) or to human serum albumin alone (HSAi, n = 26), received (i.m.): 1) 25 mg recombinantly derived methionyl somatotropin (rbST, n = 14; sometribove provided by Monsanto Co., St. Louis, MO); 2) 1100 IU eCG (n = 10); 3) rbST and eCG (rbST-eCG, n = 15); or 4) vehicle (VEH, n = 17) at 0 and 24 h after receiving prostaglandin F2 alpha (PGF2 alpha). Serum samples were collected at 0 and 40 h after PGF2 alpha, and the ovary bearing the largest follicle (DOM) was removed 44.0 +/- 0.5 h after PGF2 alpha; FFL was harvested from DOM and the subordinate follicle (SUB). Before treatment (0 h), GRFi cows had lower serum ST (0.6 +/- 0.2 vs. 2.2 +/- 0.2 ng/ml; p < 0.01) and IGF-I (26 +/- 4 vs. 72 +/- 4 ng/ml; p < 0.01), but greater IGFBP-2 (594 +/- 48 vs. 384 +/- 52 ng/ml; p < 0.01) than HSAi cows. Serum and FFL concentrations of IGF-I or IGFBP-2 were not different between rbST- and rbST-eCG-treated cows or between VEH- and eCG-treated cows at Hour 40 after the initial treatment injection; therefore, data were combined and designated as rbST and VEH, respectively. Serum IGF-I was increased to a greater extent (percentage increase above 0 h) by rbST treatment in GRFi (362 +/- 24) than in HSAi (176 +/- 16) cows (immunization by treatment, p < 0.01). Across GRFi and HSAi, rbST lowered serum IGFBP-2 (342 +/- 31 vs. 541 +/- 27 ng/ml, rbST vs. VEH; p < 0.01). Diameters of DOM or SUB were not affected by immunization or treatment. Concentrations of IGF-I and IGFBP-3 (determined by ligand blot analysis) in FFL from both DOM and SUB were lower (p < 0.05) in GRFi than in HSAi cows. In contrast, IGFBP-2 in FFL was elevated in SUB, but not DOM, in GRFi compared to HSAi cows.(ABSTRACT TRUNCATED AT 400 WORDS)
“…Blocking GRF from reaching hypophyseal somatotrophs, either by hypothalamic deafferentation (30), HST (31-33), or active immunization against GRF (34 -36) blocks episodic GH release both in ruminants and swine. Short-term experiments indicated that active immunization against GRF retarded normal growth in cattle (37).…”
Hypothalamic hormones regulate episodic and basal secretion of hormones from the anterior pituitary gland that affect metabolism and growth in cattle. This study focused on long-term growth in young calves subjected to hypophysectomy (HYPOX), hypophyseal stalk transection (HST), and sham operation control (SOC). Cross-bred (Hereford x Aberdeen Angus) and Hereford, and Aberdeen Angus calves were HYPOX (n ϭ 5), HST (n ϭ 5), or SOC (n ϭ 8) at 146 Ϯ 2 days of age, whereas another group was HST (n ϭ 5) or SOC (n ϭ 7) at 273 Ϯ 5 days of age. Body weight was determined every 21 days from birth to 1008 days of age. Anterior vena cava blood was withdrawn at 4-day intervals from day 64 -360 for RIA of GH, TSH, T 4 , T 3 , and LH, and at 20-min intervals for 480 min to determine episodic hormone secretion. Daily feed intake was determined in HST and SOC calves during an 80-day period. Birth weight averaged 35 Ϯ 1 kg (Ϯ SE) and was 142 Ϯ 4 kg at 126 days and 208 Ϯ 8 kg at 252 days before surgery. From day 146-1008, growth was arrested (P Ͻ 0.001) in HYPOX (0.06 Ϯ 0.01 kg/day) compared with SOC (0.50 Ϯ 0.04 kg/day) calves. Growth continued but at a significantly lower rate (P Ͻ 0.05) in calves HST at 146 days (0.32 Ϯ 0.07 kg/day) and 273 days (0.32 Ϯ 0.06 kg/day) compared with SOC (0.50 Ϯ 0.09 kg/day). Growth continued to be impaired to 1008 days, but more so in those HST at 146 days (432 Ϯ 43 kg BW) than 273 days (472 Ϯ 5 kg BW) and less (P Ͻ 0.05) than SOC (586 Ϯ 37 kg BW). Daily feed intake was consistently less (P Ͻ 0.05) in HST compared with SOC calves. Although episodic GH secretion was abolished and peripheral serum GH concentration remained consistently lower in HST (2.4 ng/ml) than SOC (5.5 ng/ml; P Ͻ 0.01), the calves continued to grow throughout 1008 days. Peripheral serum TSH concentration was less (P Ͻ 0.05) HST compared with SOC calves. There was an abrupt decrease (P Ͻ 0.001) in serum T 4 (4-fold) and T 3 (3-fold) concentration after surgery that remained to 360 days in HST compared with SOC calves. At the time calves were killed, pituitary gland weight was markedly reduced (P Ͻ 0.001) in HST (0.18 Ϯ 0.01 g/100 kg BW) compared with SOC (0.54 Ϯ 0.03 g/100 kg BW). Histological examination of pituitary glands from HST calves indicated the persistence of secretory GH and TSH cells in the same areas of the adenohypophysis as SOC calves. Coronal sections of the gland stained with performic acid-Alcian blue-periodic acid-Schiff-orange G, revealed GH and TSH secreting cells in HST calves similar to controls. These results indicate that long-term growth continues, but at a slower rate, after hypophyseal stalk transection of immature calves in spite of complete abolition of episodic GH secretion and consistently decreased basal secretion of GH, TSH, T 4 , and T 3 compared with sham-operated animals. Growth was abolished after hypophysectomy of immature calves in which circulating GH and TSH was undetectable. (Endocrinology 140: [2405][2406][2407][2408][2409][2410][2411][2412][2413][2414] 1999)
“…Secretion of GH from somatotrophs is regulated by growth hormone-releasing hormone (GHRH) secreted from neuronal terminals adjacent to capillaries of the hypothalamic-hypophyseal portal system in the infundibulum [3–4]. In cattle, the endocrine relevance of GHRH for anterior pituitary gland secretion of GH is demonstrated by observations that concentrations of GH in circulation are reduced in animals immunized against GHRH [5–7]. However, release of GH is also influenced by many other factors of peripheral and hypothalamic origin, including somatostatin, IGF-I, leptin, neuropeptide Y (NPY), ghrelin, and opioids [8–10].…”
Objectives were to 1) characterize the relationship of third-ventricle (IIIV) cerebrospinal fluid (CSF) concentrations of growth hormone releasing hormone (GHRH) with concentrations of GH in the peripheral circulation, and 2) assess the influence of acute administration of appetite-regulating peptides, leptin (anti-orexigenic) and neuropeptide Y (NPY; orexigenic) on release of GHRH. Six mature beef cows fitted with IIIV and jugular vein cannulae were treated intracerebroventricularly with saline, and leptin (600 μg) and NPY (500 μg) in saline, in a replicated 3 x 3 Latin square design. Third-ventricle CSF and blood were collected 10 min before and continued 220 min after treatments. Mean concentrations of GHRH and frequency of pulses after treatments were 2.2 ± 0.13 ng/mL and 1.2 ± 0.15 pulses/220 min, respectively. These measures were not influenced by treatments. Concentrations of GHRH in CSF were weakly correlated (r = 0.15; P < 0.03) with serum concentrations of GH; however, 58% of the GH pulses were preceded by a pulse of GHRH and 90% of the GHRH pulses occurred within 20 min preceding a pulse of GH. Leptin tended (P < 0.10) to suppress GH area under the curve (AUC) compared to saline. Concomitantly, NPY tended (P < 0.10) to increase GH AUC, which appeared to be a consequence of increased (P < 0.05) pulse amplitude. Infusion of NPY also increased (P < 0.05) AUC of GHRH relative to saline. No differences were detected among treatments in serum concentrations of IGF-I or its AUC. Sampling CSF from the IIIV appears to be a viable procedure for assessing hypothalamic release of GHRH coincident with anterior pituitary gland secretion of GH in cattle. These data also demonstrate the differential responsiveness of the GH axis to appetite-regulating peptides.
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