THE INFLUENCE OF HYPOPHYSECTOMY ON NSILA CONCENTRATIONS IN THE DOG: EVIDENCE FOR PARTIALLY PITUITARY-INDEPENDENT REGULATION

1977 ◽  
Vol 86 (3) ◽  
pp. 498-503 ◽  
Author(s):  
J. E. Eigenmann ◽  
M. Becker ◽  
B. Kammermann ◽  
J. Zapf ◽  
W. Leemann ◽  
...  

ABSTRACT Non-suppressible insulin-like activity (NSILA) was determined in 5 dogs before and after hypophysectomy. All NSILA determinations were carried out on serum samples after acidic Sephadex G-50 chromatography by two different assay systems, i. e. a bioassay and a protein binding assay. The levels of NSILA decreased significantly after hypophysectomy and returned to near normal levels after 2 weeks. T3−, T4− and cortisol levels were drastically reduced during the entire period of the experiment. Several GH determinations after hypophysectomy revealed very low levels. Insulin-induced hypoglycaemia failed to provoke a rise of GH levels as late as 4 months after hypophysectomy. These findings indicate that: 1) The pituitary gland cannot be the site of synthesis of NSILA. 2) NSILA concentrations in the dog are maintained at a near normal level in the presence of very low growth hormone and thyroid hormone concentrations, so that these latter hormones do not appear to be the only regulatory factors concerned in NSILA synthesis.

1979 ◽  
Vol 90 (3) ◽  
pp. 414-420 ◽  
Author(s):  
Knud W. Kastrup ◽  
Jürgen Zapf

ABSTRACT Severe growth retardation is found in patients with high levels of growth hormone and low sulphation factor activity or somatomedin. Also nonsuppressible insulin-like activity (NSILA-s) has been found to be very low in a patient with this condition as measured by bioassay, protein binding assay and radioimmunoassay and to be below activities found in hypopituitary patients. Partially purified NSILA-s restored the ability of serum to increase sulphation activity although full restitution may still depend on other factors. These findings support the hypothesis that NSILA-s belongs to the family of somatomedin and thus is involved in promoting growth, and that low activity of these growth factors is a primary cause of the growth retardation found in these patients.


1977 ◽  
Vol 85 (4) ◽  
pp. 818-822 ◽  
Author(s):  
J. E. Eigenmann ◽  
M. Becker ◽  
B. Kammermann ◽  
W. Leemann ◽  
R. Heimann ◽  
...  

ABSTRACT Non-suppressible insulin-like activity (NSILA-S) was determined in 5 dogs before and after pancreatectomy and again during insulin therapy. All NSILA-S determinations were carried out on serum samples which were passed over Sephadex G-50 columns equilibrated with 1 m acetic acid. The levels of NSILA-S decreased drastically shortly after pancreatectomy and rose slowly after institution of insulin therapy, to normal levels. During the period of severe diabetes after pancreatectomy the concentration of growth hormone was elevated. These findings indicate that 1) the pancreas cannot be the site of synthesis and release of NSILA-S, 2) NSILA-S levels do not always parallel growth hormone levels and 3) the synthesis and secretion of NSILA-S among other factors is under the control of insulin.


1992 ◽  
Vol 12 (6) ◽  
pp. 2624-2632
Author(s):  
D Murphy ◽  
K Pardy ◽  
V Seah ◽  
D Carter

In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone-depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins.


1977 ◽  
Vol 23 (4) ◽  
pp. 677-682 ◽  
Author(s):  
Juergen Zapf ◽  
Ueli Kaufmann ◽  
Eugen J Eigenmann ◽  
E Rudolf Froesch

Abstract We describe a sensitive protein-binding assay for non-suppressible insulin-like activity in human serum. It can detect as little as 0.2 microunits (corresponding to 0.5 ng) of the activity in 0.4 ml of the assay mixture. It is measured in a low-molecular-weight fraction (termed "biological material") obtained by chromatography of serum on Se¬phadex G-50 in 1 mol/liter acetic acid. This fraction has been shown earlier to contain nearly all this biologically active material that is present in serum. A partially purified carrier protein from human serum is used as the binding protein; different concentrations of a partially purified preparation of material with the activity serve as standards, which compete with 1251-labeled tracer for binding. Bio¬logical material dilutes more or less in parallel with the standard over a 10-fold concentration range. In the chro¬matographed serum fractions, displacing activity appears between 50 and 80% bed volume, with the peak at 60%, and coincides with the distribution and the peak of radio¬activity obtained by chromatography of tracer. A good correlation (γ = 0.88) is observed between the values determined for this activity in the rat fat-pad assay and the protein-binding assay, although the latter yields about twofold higher results (160 ± 37 milliunits/liter vs. 345 ± 65 milliunits/liter, mean values for 18 normal sera). Values determined in the protein-binding assay are decreased in hypopituitary patients (183 ± 27 milliunits/liter) and in¬creased in acromegalics (486 ± 88 milliunits/liter), in accord with the results of the bioassay (68 ± 21 milli-units/liter for hypopituitary patients, 293 ± 53 for acro¬megalics).


2005 ◽  
Vol 153 (5) ◽  
pp. 643-649 ◽  
Author(s):  
Anne Lene Dalkjær Riis ◽  
Troels Krarup Hansen ◽  
Steffen Thiel ◽  
Claus Højbjerg Gravholt ◽  
Signe Gjedde ◽  
...  

Background: Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields. Methods: To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves’ hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic auto-immune thyroiditis before and after L-thyroxine substitution. Results: In all hyperthyroid patients, MBL levels were increased – median (range), 1886 ng/ml (1478–7344) – before treatment and decreased to 954 ng/ml (312–3222) after treatment (P = 0.01, paired comparison: Wilcoxon’s signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312–1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356–2488) (P = 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20–457) compared with 979 ng/ml (214–1533) after L-thyroxine substitution (P = 0.03, paired comparison: Wilcoxon’s signed ranks test). Conclusion: Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.


Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1229-1239
Author(s):  
D. Acampora ◽  
S. Mazan ◽  
F. Tuorto ◽  
V. Avantaggiato ◽  
J.J. Tremblay ◽  
...  

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1−/− mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1−/− mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.


1977 ◽  
Vol 84 (1) ◽  
pp. 167-176 ◽  
Author(s):  
C. E. Martin ◽  
M. H. Cake ◽  
P. E. Hartmann ◽  
I. F. Cook

ABSTRACT The concentration of total corticosteroids, corticosteroid binding globulin (CBG) and progesterone were determined in maternal and foetal/neonatal plasma from rats on days 5, 4, 3, 2, 1 before birth and days 0, 1, and 4 after birth. In addition free corticosteroids and adrenal weight/unit body weight were measured on the foetuses/neonates and the foetuses, respectively. Although the concentration of maternal total corticosteroids and CBG ranged from 53.0 ± 12.5 to 31.0 ± 13.1 μg/100 ml (x̄ ± sem) and 26.6 ± 2.2 to 45.1 ± 0.9 μg corticosteroid bound/100 ml plasma, respectively, the changes in the concentration of these constituents were not related to the initiation of either parturition or lactation. The concentration of total corticosteroids in foetal plasma increased significanly (P < 0.05) from day 5 (14.6 μg/100 ml) to reach peak concentrations (44.9 μg/100 ml) on day 3 before birth and then decreased to low levels (7.7 μg/100 ml) at birth. The pattern of change in foetal adrenal weight/unit body weight closely followed the pattern of change in the concentration of total corticosteroids in foetal plasma during the last 5 days of gestation. There was a significant (P < 0.05) daily decrease in the concentration of CBG in the foetuses from 4 days before until 1 day before birth, which resulted in a significant (P < 0.01) increase from 3.08 to 5.94 μg/100 ml of free corticosteroids in the foetal plasma between day 2 and day 1 before birth, respectively. This peak corresponded with a significant fall (P < 0.02) in the maternal progesterone (measured by protein binding assay) from 2.57 μg/100 ml to 0.62 μg/100 ml between day 2 and day 1 before birth. Foetal progesterone (measured by radioimmunoassay) showed the same changes as maternal progesterone but was between 25–50 % of that in maternal plasma. These findings suggest that the changes in foetal free corticosteroids and maternal progesterone are important in the initiation of parturition in the rat.


1992 ◽  
Vol 12 (6) ◽  
pp. 2624-2632 ◽  
Author(s):  
D Murphy ◽  
K Pardy ◽  
V Seah ◽  
D Carter

In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone-depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins.


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