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Query: UMLS:C0432222 (SEM)
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Placental growth hormone (PGH) progressively replaces pituitary growth hormone in the maternal circulation from mid-gestation onwards in human pregnancy. Our previous investigations have shown that placental growth hormone concentrations correlate well with foetal growth. Despite the apparent correlation between PGH and birthweight, the physiology of its secretion during pregnancy has not been well defined. We investigated the response of maternal serum PGH to oral glucose loading in pregnant women (n = 24) who demonstrated normal glucose tolerance at a mean gestation of 29 weeks. Mean (SEM) fasting PGH concentrations were high (36.9 [6.4] ng/ml). No suppression of PGH was noted at one, two or three hours after a 75 g oral glucose load. Similarly, no changes were noted in growth hormone binding protein or in calculated free PGH over the course of the glucose tolerance test. As expected, insulin concentrations rose sixfold and insulin like growth factor binding protein 1 concentrations fell by 20 % with glucose loading. Correlation analysis showed maternal weight, BMI, fasting serum glucose serum insulin to be significantly correlated with the babies' birthweight. Our results support the proposition that PGH concentrations in maternal serum are not suppressed by oral glucose loading in non-diabetic mothers.
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PMID:Placental growth hormone is not suppressed by oral glucose loading in normal human pregnancy. 1206 38

Organs that respond to and metabolize GH are enriched in cognate high-affinity receptors. However, whether isologous receptors mediate the de facto access of ligand to cellular degradative pathways is not known. To address this query, we assessed the distribution and whole-body elimination kinetics of (endogenous and exogenous) GH before and after administration of a novel, potent, and selective recombinant human (rh) GH receptor antagonist peptide, pegvisomant. Sixteen healthy young adults (nine men and seven women) participated in a double-blind, prospectively randomized, within-subject cross-over study. The intervention comprised a single sc injection of placebo vs. a high dose of pegvisomant (1 mg/kg sc) timed 62 and 74 h before the overnight sampling and daytime infusion sessions, respectively. The half-life, metabolic clearance rate (MCR), and distribution volume of GH were quantitated by way of: 1) deconvolution analysis of serum GH concentration time series collected every 10 min for 10 h; 2) exponential regression analysis of the decay of GH concentrations after a 6-min iv pulse of rhGH (1 and 10 micro g/kg); 3) calculation of the MCR during constant iv infusion of rhGH (0.5 and 5.0 micro g/kg every 2 h); and 4) exponential fitting of the elimination time-course of GH concentrations following cessation of each constant infusion. Concentrations of GH and pegvisomant were measured in separate, noncross-reactive, two-site monoclonal, immunofluorometric assays. Pegvisomant concentrations averaged 4860 +/- 480 micro g/liter (+/-SEM) across the infusion interval, thus exceeding low steady state GH concentrations by 3000-fold. Inhibitory efficacy of the GH receptor antagonist peptide was affirmed by way of a 34% reduction in the serum total IGF-I concentration, i.e., from 257 +/- 37 (placebo) to 170 +/- 24 (drug) micro g/liter (P < 0.001); and a reciprocal 77% elevation of the (10-h) mean GH concentration, i.e., from 1.3 +/- 0.23 (placebo) to 2.3 +/- 0.42 (drug) micro g/liter (P = 0.003). ANOVA disclosed that prior administration of pegvisomant (compared with placebo) did not alter: 1) the calculated half-life (minutes) of secreted GH, which averaged 15 +/- 1.3 (placebo) and 14 +/- 0.69 (drug); 2) the half-time of disappearance (minutes) of an iv pulse of rhGH, 15 +/- 1.0 (placebo) and 13 +/- 0.5 (drug) (for the 10 micro g/kg dose); 3) the distribution volume (milliliters per kilogram) of rhGH, 59 +/- 6.2 (placebo) and 58 +/- 3.5 (drug); 4) the steady state GH concentration (micrograms per liter) attained during constant iv infusion of rhGH (at a rate of 5 micro g/kg every 2 h), 18.2 +/- 2.4 (placebo) and 18.3 +/- 2.3 (drug); 5) the half-life (minutes) of elimination of GH from equilibrium, 16 +/- 0.98 (placebo) and 16 +/- 1.8 (drug); and 6) the steady state MCR (liters per kilogram per day) of rhGH, 3.8 +/- 0.32 (placebo) and 3.5 +/- 0.31 (drug). In ensemble, the present data refute the a priori postulate that vascular-accessible GH receptors determine the in vivo pseudoequilibrium kinetics of GH disappearance in the human.
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PMID:Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men. 1246 80


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