In-vivo uptake of human growth hormone in male rat liver

1989 ◽  
Vol 121 (1) ◽  
pp. 19-25 ◽  
Author(s):  
F. Bullier-Picard ◽  
M. C. Postel-Vinay ◽  
C. Kayser
Keyword(s):  
Plasma Membranes ◽  
Human Growth ◽  
Rat Hepatocytes ◽  
Male Rats ◽  
Male Rat ◽  
Liver Homogenates ◽  
Isopycnic Centrifugation ◽  
Specific Labelling ◽  
In Vivo Uptake

ABSTRACT 125I-Labelled human GH (hGH) was injected i.v. to male rats and its subcellular distribution in the hepatocyte was examined using fractionation techniques. Uptake into liver homogenates was maximal by 15 min after injection and represented 24% of the injected radioactivity; it was markedly inhibited by coinjection of native hGH. 125I-Labelled hGH taken up by the liver underwent a time-dependent translocation process. The peak of specific labelling of plasma membranes occurred at 3 min whereas later on the radioactivity was concentrated in low-density structures present in Golgi-endosome fractions. To characterize the ligand-associated structures better, endosome-enriched fractions were prepared from a microsomal fraction by isopycnic centrifugation in a sucrose gradient and a Nycodenz gradient. The radioactivity was in one peak with a median density of 1·096 g/cm3 in the Nycodenz gradient fractions. The peak of radioactivity was distinct from that of galactosyltransferase activity which appeared at a median density of 1·114 g/cm3. The labelled material eluted from the various subcellular fractions appeared as intact hGH. Upon in-vivo interaction with male rat hepatocytes, 125I-labelled hGH was internalized with a sequential association with plasma membranes and endocytic structures distinct from Golgi elements. Journal of Endocrinology (1989) 121, 19–25

scholarly journals In vivo uptake of [14C]leucine by skeletal muscle ribosomes after injury in rats fed two levels of protein

1969 ◽  
Vol 23 (2) ◽  
pp. 271-280 ◽  
Author(s):  
V. R. Young ◽  
P. C. Huang
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Male Rats ◽  
Thigh Muscle ◽  
Left Femur ◽  
The Right ◽  
And Control ◽  
The Relationship ◽  
In Vivo Uptake

1. After 14 days on a diet containing 5 or 25% casein male rats received a fracture of the left femur. Four hours before they were killed the injured and control rats were injected with [1-14C]leucine; the incorporation of radioactivity into an isolated fraction of skeletal muscle ribosomes was studied 6, 12, 24, 48, 72, 96 and 228 h after injury.2. The incorporation of [14C]leucine into the ribosome fraction in right thigh muscles dropped to 40% of control values 72 h after fracture in well-nourished rats and after 96 h with diets containing 5 or 25%, casein.3. The specific activity of the trichloroacetic acid-soluble fraction of muscle from injured rats was equal to or higher than that of the controls during the first 72 h but lower at 96 h.4. These results suggest that a reduced incorporation of amino acids by ribosomes from the right thigh muscle occurred on day 3 after fracture in the group receiving 25% casein but not in the group receiving 5% casein.5. Muscle RNA and DNA concentrations were not affected by the injury.6. The relationship between these findings and the loss of muscle N after injury is discussed.

Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro

1987 ◽  
Vol 253 (5) ◽  
pp. E508-E514
Author(s):  
J. Weiss ◽  
M. J. Cronin ◽  
M. O. Thorner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Male Rat ◽  
Base Line ◽  
Additive Effects ◽  
Growth Hormone Releasing Factor ◽  
The Impact

Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal.

Quantification of the Uncertainties in Extrapolating From In Vitro Androgen Receptor Antagonism to In Vivo Hershberger Assay Endpoints and Adverse Reproductive Development in Male Rats

2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Adverse Outcome ◽  
In Utero ◽  
Male Rats ◽  
Male Rat ◽  
Rat Offspring ◽  
Hershberger Assay ◽  
Key Events

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of < 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.

AN AUTORADIOGRAPHIC STUDY ON THE LOCALIZATION OF ANDROGEN IN THE PROSTATE GLAND AND THE SEMINAL VESICLES OF THE MALE RAT

1970 ◽  
Vol 63 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Kjell J. Tveter
Keyword(s):  
Epithelial Cells ◽  
Prostate Gland ◽  
Autoradiographic Study ◽  
Seminal Vesicles ◽  
Radioactive Material ◽  
Male Rats ◽  
Male Rat ◽  
Selective Localization ◽  
Qualitative Pattern

ABSTRACT The distribution of radioactive material in the prostate gland and the seminal vesicles has been studied by autoradiography after intramuscular administration of [1,2-3H] testosterone in vivo to adult castrated male rats. Positive autoradiographs were obtained from 7½ min to 8 h after the administration. As early as after 15 min, there appeared to be a selective localization of radioactivity in the epithelial cells, with much of the labelling associated with the nuclei; the stromal labelling was markedly less. This picture was even more significant ½, 1 and 2 h after the injection, when the autoradiographs demonstrated a preferential labelling of the nuclei of the epithelial cells. A distinct labelling of the epithelial cells was also found 8 h after the injection. The same qualitative pattern of distribution of radioactivity was seen in the four prostatic lobes and the seminal vesicles. No significant labelling of the secretions in the glandular lumina was observed.

Effects of hypophysectomy and GH administration on bovine and human GH binding to rat liver membranes

1985 ◽  
Vol 249 (1) ◽  
pp. E56-E62
Author(s):  
J. L. Messina ◽  
S. Eden ◽  
J. L. Kostyo
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Specific Binding ◽  
Human Growth ◽  
Male Rats ◽  
Normal Male ◽  
Number Of Binding Sites ◽  
Liver Membranes ◽  
Isolated Liver

Experiments were conducted to investigate the specific binding of highly purified bovine and human growth hormones (bGH and hGH) to purified liver plasma membranes of male rats at various times after hypophysectomy and after the acute intravenous administration of bGH. Liver membranes prepared from hypophysectomized male rats showed a two- to threefold increase in the specific binding of either [125I]iodo-bGH or [125I]iodo-hGH, when compared with membranes prepared from the livers of age-matched normal male rats. The increase in GH binding was apparent within 3 days after hypophysectomy and persisted for a number of weeks after the operation. The increase in GH binding produced by hypophysectomy appeared to be due to an increase in the number of binding sites present on the membranes. The intravenous injection of 200 micrograms of bGH into hypophysectomized male rats 5-60 min before they were killed markedly reduced the ability of liver membranes prepared from these animals to bind [125I]iodo-bGH specifically. This decrease in GH binding seen after the injection of bGH may have been due to the development of a slowly dissociating hormone-binding site complex, which thereby reduced the number of available binding sites. This conclusion is supported by the finding that bGH, which is bound in vitro to isolated liver membranes, dissociates slowly and incompletely in the presence of an excess of unlabeled hormone. Moreover, the degree to which the bound hormone can dissociate appears to depend on the length of time that association is allowed to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

AN EXPERIMENTAL ANALYSIS OF THE EFFECTS OF OESTROGEN ON THE THYROID GLAND OF CASTRATED ADULT MALE RATS

1968 ◽  
Vol 40 (4) ◽  
pp. 397-408 ◽  
Author(s):  
J. F. BITHELL ◽  
K. BROWN-GRANT
Keyword(s):  
Thyroid Gland ◽  
Rate Constant ◽  
Adult Male ◽  
Time Course ◽  
Hormone Secretion ◽  
Male Rats ◽  
Male Rat ◽  
Exit Rate ◽  
Experimental Conditions

SUMMARY The uptake of 131I by the thyroid gland of the castrated adult male rat is increased 24 hr. and is maximal 48 hr. after the injection of a single dose of 50 μg. oestradiol. The response is not dose-dependent between 25 and 1600 μg. The thyroid:serum (T:S) concentration ratio for 131I is also increased by oestradiol with a time-course similar to the changes in uptake, but release of 131I-labelled hormone from the gland in vivo and radioactive phosphate uptake were not affected. Analysis of the kinetics of 131I accumulation by the blocked gland show that the effects on 131I uptake and T:S ratio were due to an increase in the clearance rate with a possible associated decrease in the exit rate constant for iodide from the gland to the blood. Under the conditions of these experiments, the effects of oestradiol are not consistent with their being produced by an increase in pituitary thyrotrophic hormone secretion; a direct action on the gland appears likely. These conclusions apply solely to the experimental conditions described here and do not provide the basis for any generalization about the action of oestrogens on the thyroid gland. The method of analysis developed for the estimation of the unilateral clearance constant and the exit rate constant, together with their standard deviations, is presented in an appendix.

Significance of experimental studies for assessing adverse effects of endocrine-disrupting chemicals

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2125-2141 ◽  
Author(s):  
L. E. Gray ◽  
P. M. D. Foster
Keyword(s):  
Adverse Effects ◽  
Statistical Power ◽  
Experimental Studies ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Tier 2 ◽  
In Vivo Assays ◽  
Endocrine Disrupting

The U.S. Environmental Protection Agency (USEPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce androgen (AR) and estrogen (ER) receptor-mediated effects in mammals and other animals. The utility of this approach is based upon the knowledge that mechanisms of endocrine-disrupting chemical (EDC) action are highly conserved at the cellular and molecular levels among vertebrates. Some EDC mechanisms also are shared with invertebrates. High-priority chemicals would be evaluated in a Tier 1 screening (T1S) battery, and chemicals that are positive in T1S would then be tested in Tier 2 (T2). T1S includes in vitro ER and AR receptor binding and/or gene expression, an assessment of steroidogenesis and mammalian (rat) and nonmammalian (fish) in vivo assays. In vivo, the uterotropic assay detects estrogens and antiestrogens, while steroidogenesis, antithyroid activity, antiestrogenicity, and HPG function are assessed in a pubertal female assay. Antiandrogens are detected in the Hershberger assay (weight of androgen-dependent tissues in castrate-immature-male rats). Fish and amphibian assays are also being developed to identify EDCs. Several alternative mammalian in vivo assays have been proposed. Of these, a short-term pubertal male rat assay appears most promising. T1S is designed to be sensitive to EAT activities, but many of the effects detected at the screening level would not be considered adverse, the dosage levels may be high, and the route of administration used may not be the most relevant. However, issues of adversity, dose response, and route(s) of exposure would be resolved in the testing phase. In addition to using an enhanced multigenerational test for Tier 2, an in utero-lactational screening protocol is also being evaluated by USEPA for use in T2 or T1S. For T2, the numbers of endocrine-sensitive end-points and offspring (F1) examined in multigenerational tests need to be expanded for EDCs in a thoughtful manner, based in part upon the results of T1S. In addition, for some chemicals histological examination of 10 adult F1 per sex in only the control and high-dose groups provides inadequate statistical power to detect low-dose lesions induced during development. In these cases, we propose that all the offspring be examined after puberty for gross and histological reproductive abnormalities. Since EDCs, like the phthalates and AR-antagonists, produce characteristic profiles, or syndromes, of adverse effects, data need to be reported in a manner that clearly identifies the proportion of animals displaying one or more of the abnormalities in a syndrome. Consideration should be given to tailoring T2, based on the results of T1S to assure that all of the effects in such chemically induced developmental syndromes are included in the study.

ATRIAL NATRIURETIC PEPTIDE IS A PHYSIOLOGICAL INHIBITOR OF ACTH RELEASE: EVIDENCE FROM IMMUNONEUTRALIZATION IN VIVO

1991 ◽  
Vol 131 (3) ◽  
pp. R9-R12 ◽  
Author(s):  
G. Fink ◽  
R.C. Dow ◽  
D. Casley ◽  
C.I. Johnston ◽  
A.T. Lim ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Acth Secretion ◽  
Acth Release ◽  
Atrial Natriuretic

ABSTRACT The brain is thought to exert a predominantly stimulatory action on ACTH secretion mediated mainly by corticotrophin-releasing factor-41 (CRF-41) and arginine vasopressin (AVP). Several data, however, also point to the existence of an ACTH-inhibiting factor. Atrial natriuretic peptide (ANP), at concentrations found in hypophysial portal blood, inhibits ACTH release in vitro. The aim of the present studies was to use ANP immunoneutralization to determine whether ANP does in fact inhibit ACTH release in vivo. Intracerebroventricular infusion (I μl/min for 30 min) of sheep anti-ANP serum into male rats anaesthetized with sodium pentobarbitone had no significant effect on jugular venous plasma concentrations of ACTH or LH but did decrease significantly the plasma concentrations of prolactin. Intravenous infusion of 0.8 ml sheep anti-ANP serum but not control (non-immune) sheep serum, through an indwelling intra-atrial cannula in conscious male rats resulted in a marked and significant increase in plasma ACTH and corticosterone concentrations. The ACTH and corticosterone response to a 30-s ether stress was not significantly potentiated in the same conscious rats infused with anti-ANP serum. Intra-atrial infusion of anti-ANP did not significantly affect plasma prolactin, LH, glucose or sodium concentrations or plasma osmolality. These results show for the first time that ANP is a potent inhibitor of ACTH secretion in the conscious male rat and that, therefore, ANP is a hypothalamic neurohormone which is likely to play an important inhibitory role in the neural control of ACTH release.

THE EFFECT OF 2-BROMO-α-ERGOCRYPTINE (CB154) ADMINISTRATION ON THE HORMONE LEVELS, ORGAN WEIGHTS, PROSTATIC MORPHOLOGY AND ZINC CONCENTRATIONS IN THE MALE RAT

1976 ◽  
Vol 83 (1) ◽  
pp. 211-224 ◽  
Author(s):  
M. E. Harper ◽  
V. Danutra ◽  
J. A. Chandler ◽  
K. Griffiths
Keyword(s):  
Prostatic Tissue ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Prolactin ◽  
Cell Organelles ◽  
Adenyl Cyclase Activity ◽  
Zinc Concentrations ◽  
High Concentrations

ABSTRACT 2-Bromo-α-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.

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