The effect of hypophysectomy and growth hormone replacement on albumin synthesis and catabolism in the rat.
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ABSTRACT:
SUBMITTER: Kernoff LM
PROVIDER: S-EPMC1177221 | biostudies-other | 1971 Sep
REPOSITORIES: biostudies-other
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Project description:1. The influence of pituitary gonadotrophins and of testosterone on the conversion of linoleic acid into other polyunsaturated fatty acids by rat testicular tissue was studied. 2. In immature hypophysectomized rats, follicle-stimulating hormone caused a threefold increase in the incorporation of radioactivity from [1-(14)C]linoleic acid into testicular lipids; the distribution of (14)C in the polyunsaturated fatty acids, however, was not significantly affected. 3. In mature hypophysectomized rats, the hormonal treatments had less pronounced effects on (14)C incorporation into testicular lipids, but caused a significant increase in the percentage of (14)C incorporated into polyunsaturated fatty acids of the omega-6 series, luteinizing hormone and testosterone having the more pronounced influences. 4. A time-course study of the appearance of radioactivity in the ejaculated spermatozoa of rabbits, after they had been given a tracer dose of [1-(14)C]linoleic acid, indicated that incorporation of radioactivity into spermatozoa occurred during all stages of spermatogenesis.
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Project description:1. The effects of hypophysectomy and replacement therapy with sheep prolactin and bovine growth hormone on the lactose synthetase activity of the mammary glands of lactating rabbits were studied. 2. There was an approximately fourfold decline in the lactose synthetase activity of homogenates calculated on a DNA basis within 6-7 days of hypophysectomy. Prolactin reversed this decline but growth hormone had no effect. 3. Changes in the properties of a particulate fraction isolated from the glands indicated that a decline in the effective concentration of alpha-lactalbumin was one factor contributing to the decreased lactose synthetase activity after hypophysectomy. 4. As the changes in lactose output produced by hypophysectomy and prolactin therapy are much greater than the changes in total lactose synthetase activity it is concluded that the activity of this enzyme is not the main factor controlling lactose output under these conditions.
| S-EPMC1174549 | biostudies-other
Project description:A method described by McFarlane (1963a) for the measurement of the absolute rate of synthesis of liver-made plasma proteins was used to show that, within a few hours of giving bovine growth hormone to rats, fibrinogen synthesis increased significantly without a change in albumin synthesis.
| S-EPMC1179345 | biostudies-other
Project description:The effect of hypophysectomy on the protein metabolism of the liver in vivo was studied. Fractional rates of protein synthesis and degradation were determined in the livers of normal and hypophysectomized rats. Synthesis was measured after the injection of massive amounts of radioactive leucine. Degradation was estimated either as the balance between synthesis and accumulation of stable liver proteins or from the disappearance of radioactivity from the proteins previously labelled by the injection of NaH14CO3. The results indicate that: (1) hypophysectomy diminishes the capacity of the liver to synthesize proteins in vivo, mainly of those that are exported as plasma proteins; (2) livers of both normal and hypophysectomized rats show identical protein-degradation rates, whereas plasma proteins are degraded slowly after hypophysectomy.
| S-EPMC1186573 | biostudies-other
Project description:Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600.
| S-EPMC10522239 | biostudies-literature
Project description:The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency.
| S-EPMC5348436 | biostudies-literature
Project description:BACKGROUND:The aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment. METHODS:A randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of -?2 to -?1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires. RESULTS:Data from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor. CONCLUSIONS:The adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor. TRIAL REGISTRATION:This study is registered with ClinicalTrials.gov , number NCT01877512.
| S-EPMC6035403 | biostudies-literature
Project description:Background & aimsEffective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF.MethodsTen adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE).ResultsPatients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n = 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6 mg/ml to 18.9±1.7 mg/ml; p = 0.003), fatty acid-binding capacity (8.2±1.4 μM to 3.1±1.5 μM; p = 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5 mg/ml to 14.6±1.6 mg/ml; p = 0.001). Native albumin levels were increased throughout day 1-11 PE-A5% sessions (6.5±1.0 mg/ml to 10.2±1.4 mg/ml; p = 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none).ConclusionsPE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF.Impact and implicationsAcute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF.Clinicaltrialsgov identifierNCT01201720.Eudract number2010-021360-15.
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Project description:Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (?IMCL, ?IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ?IMCL and ?IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.
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Project description:1. The isolated perfused rat liver was used to study degradation rates of plasma albumin, transferrin and fibrinogen. 2. Constant fractional rates were observed for all three proteins even when the albumin concentration was drastically increased by the addition of large amounts to the perfusate pool. 3. Livers taken from rats deprived of dietary protein for 14-18 days showed greatly diminished fractional catabolic rates for albumin when perfused with blood from similarly deprived animals. 4. These rates could be restored to near-normal values by adding albumin or by perfusing with blood from normally fed rats. 5. These findings are consistent with the theory of pinocytosis as a step in the degradation of plasma proteins by hepatic parenchymal cells.
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