96 research outputs found
Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice
OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a
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Purification of Luteinizing Hormone-Releasing Factor from Bovine Hypothalamus
Determinants of GH-releasing hormone and GH-releasing peptide synergy in men
Age, sex steroids, and abdominal-visceral fat (AVF) jointly affect pulsatile growth hormone (GH) secretion. Pulsatile GH secretion in turn is controlled by GH-releasing hormone (GHRH), GH-releasing peptide (GHRP), and somatostatin. Marked stimulation of pulsatile GH secretion is achieved via GHRH-GHRP synergy. Nonetheless, how key modulators of GH secretion, such as age, sex steroids, and body mass index, modify GHRH-GHRP synergy is not known. The present strategy was to 1) infuse GHRH and GHRP-2 simultaneously to evoke synergy and 2) downregulate the gonadal axis with leuprolide and then restore placebo (Pl) or testosterone (T) to clamp the sex steroid milieu. Forty-seven men [18–74 yr of age, T = 7–1,950 ng/dl, estradiol (E2) = 5–79 pg/ml, insulin-like growth factor (IGF)-I = 115–817 μg/l, AVF = 11–349 cm2] were studied. GHRH-GHRP synergy correlated negatively with age and AVF (both P < 0.001) and positively with IGF-I (P < 0.001) and IGF-binding protein (IGFBP)-3 (P = 0.031). Unstimulated basal (nonpulsatile) GH secretion correlated positively with T (P = 0.015) and E2 (P = 0.004) concentrations. Fasting pulsatile GH secretion varied negatively with age (P = 0.017) and positively with IGF-I (P = 0.002) and IGFBP-3 (P = 0.001). By stepwise forward-selection multivariate analyses, AVF, IGF-I, and IGFBP-3 together explained 60% of the variability in GHRH-GHRP synergy (P < 0.001), E2 accounted for 17% of the variability in basal GH secretion (P = 0.007), and IGF-I explained 20% of the variability in fasting pulsatile GH secretion (P = 0.002). In conclusion, a paradigm examining GHRH-GHRP synergy under a sex steroid clamp reveals highly selective control of basal, pulsatile, and synergistic peptide-driven GH secretion by AVF, E2, and IGF-I in healthy men
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Antagonists of LHRH
LHRH analogs and congeners with high water solubility have been synthesized. These new analogs had 0%-100% antiovulatory activity at a 0.5 .mu.g dosage and 0%-80% at 0.25 .mu.g. The ED.sub.50 for histamine release was 30.5 .mu.g/ml->300 .mu.g/ml.Board of Regents, University of Texas Syste
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Thyrotropic Hormone Releasing Factor (TRF). Its Chemistry and Physiology
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Effective hormonal peptides: D-3-QA1 6-LHRH
Two sets of hormonal peptides are synthesized which are super agonists of the lutenizing hormone releasing hormone (LHRH). Chronic administration results in the inhibition of LHRH which is responsible for stimulating cell growth in the testes. One peptide has the D(dextro)-form of a mono-heterocyclic amino acid in position six (D-3-pyridyl-alanine) while the other peptide has a bi-heterocyclic amino acid in that same position (.beta.-(3-quinolyl)-D-.alpha.-alanine. Both peptides are less metabolically reactive than those in the prior art and yet both peptides are significantly more potent than LHRH itself.Board of Regents, University of Texas Syste
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