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G Hennen

Publications and source records attributed to G Hennen.

At least 91 records · Page 5Linked to original sources
PubMed1988

Cloning and nucleotide sequence of placental hGH-V cDNA.

We have previously demonstrated the presence in human placenta and maternal serum of a GH variant, called human placental growth hormone (hPGH). We have also shown that the hGH-V gene is expressed at the placental level thus possibly coding for hPGH. The hGH-V cDNA has now been isolated from a lambda gt 11 human placenta cDNA library. Its sequence has been determined which firmly establishes the GH-V gene mode of splicing as well as the GH-V protein structure. Our data give final evidence of placental hGH-V gene expression and reinforce the hypothesis of identity between the hGH-V protein and hPGH.

Amino Acid Sequence↗
PubMed1988

[Placental growth hormone. Significance relative to growth hormone and lactogen hormone].

Normal human placenta secretes within maternal compartment a pregnancy associated protein, placental growth hormone (PGH). This entity, agonist of pituitary GH, appears responsible for the elevated IGF I blood levels observed in the mother during pregnancy, while pituitary GH is no longer secreted. PGH could thus play a significant role in the anabolic processes of pregnancy. The biochemical mechanism responsible for PGH production is the expression of the GH-V gene at the placental level. This has been demonstrated by the positive probing of GH-V mRNA in this tissue, by the establishment of the restriction map and sequence of its cDNA as well as by the NH2-terminal sequence determination of both 22 and 25K PGH forms. The positive aspect of this function for human reproduction gains weight in that a placenta deleted for the CS-A, GH-V and CS-B gene expresses alternative genes coding for protein similar or related to pituitary GH or hPL, respectively.

Amino Acid Sequence↗
PubMed1987

Immunochemical mapping of a specific domain on human choriogonadotropin using anti-protein and anti-peptide monoclonal antibodies.

In an attempt to localize topographic domains specific to native human chorionic gonadotropin (hCG), we studied the discontinuous antigenic regions recognized by a monoclonal anti-hCG antibody designated as C8 which binds only to hCG and does not cross-react with either the free hCG-alpha and hCG-beta subunits or other glycoprotein hormones. Using two-site monoclonal immunoradiometric assays (M-IRMAs), we found that C8 antibody and an anti-peptide antibody (FB12) directed to residues 110-116 of hCG-beta did not bind simultaneously to hCG. This observation suggested that C8 binds to residues of hCG-beta included either in the antibody-binding region of FB12 or in close proximity to amino acids 110-116. To further delineate the regions of hCG-beta recognized by C8, we carried out hapten inhibition experiments with synthetic peptides corresponding to various regions of hCG-beta. The peptide corresponding to residues 109-122 and subpeptides (111-122 or 112-122) inhibited the binding of 125I-hCG to C8, whereas weak inhibition was observed with subpeptide 113-122. By studying the binding of C8 to the 1-112 disulfide-bonded part of hCG-beta (hCG-beta core) recombined with hCG-alpha, we were able to confirm that C8 binds to a region including or near to Asp112. M-IRMAs showed that C8 does not bind to the recombinant molecule lacking residues 113-145 of hCG. Taken together, these results indicate that a limited number of residues located on hCG-beta near to Asp112, and most likely the sequence Asp111-Asp112-Pro113, are included in the discontinuous antigenic region recognized by C8. We then attempted to localize residues of hCG-alpha that constitute another part of the determinant which bound to C8. Six synthetic peptides corresponding to various regions of hCG-alpha did not inhibit binding of 125I-hCG to C8. In contrast, M-IRMAs demonstrated that C8 is capable of binding recombinant products composed of the hCG-beta subunit and the alpha subunits from human, equine, and porcine species. These results indicate that C8 recognizes a region of the alpha subunit highly conserved in these three species. Finally, we determined that the discontinuous regions recognized by C8 are partially accessible on the CG/LH-receptor complex.

Amino Acid Sequence↗
PubMed1987

Receptor binding properties and insulin-like effects of human growth hormone and its 20 kDa-variant in rat adipocytes.

The natural 20 kDa-variant of human growth hormone (hGH) binds with high affinity to IM-9 human lymphocyte receptors, in agreement with its potency in biological assays for growth promoting and lactogenic activities. In contrast, 20 kDa-hGH has only 3% of the potency of 22 kDa-hGH in binding to the receptors of normal and hypophysectomized rat adipocytes. In agreement with the binding potency, 20 kDa-hGH is only 3% as potent as 22 kDa-hGH in stimulating lipogenesis in normal rat adipocytes preincubated for a few hours in hGH-free medium. The 20 kDa-hGH is also much weaker than 22 kDa-hGH in stimulating lipogenesis in adipocytes from hypophysectomized rats. These data strongly support the concept that the rat adipocyte receptor, which mediates the insulin-like effects of growth hormone, is different from the receptor found on human IM-9 lymphocytes. Preincubation of rat adipocytes with hGH induces a refractoriness to subsequent activation of lipogenesis by hGH but does not abolish the response to insulin, while preincubation with insulin slightly potentiates the hGH response and does not change the insulin response. Additivity studies and a detailed comparison of the lipogenic effects of insulin and hGH suggest that hGH shares only a subset of the metabolic pathways activated by insulin.

Adipose Tissue↗
PubMed1987

Physiological studies of human chorionic gonadotropin (hCG), alpha hCG, and beta hCG as measured by specific monoclonal immunoradiometric assays.

Several libraries of monoclonal antibodies have been produced against epitopes that reside on hCG, alpha hCG, and beta hCG. Having characterized them physically, we explored their use in the construction of highly specific and sensitive immunoradiometric assays. There were several important immunochemical considerations with respect to developing assays that accurately detect low levels of free subunits in serum in the presence of high concentrations of the native hormone. These include physical properties and specificities of the monoclonal antibodies, choice of capture antibody on the solid phase support, assay design, and purity of hormone standards. Using such assays, we found early pregnancy (in vitro fertilization) to be characterized by the sequential appearance of hCG, followed by beta hCG and then alpha hCG. Molar ratios of beta hCG to alpha hCG and beta hCG to hCG were highest in early gestation. However, there was a reversal of the beta hCG to alpha hCG ratio at 12-13 weeks gestation, and an excess of free alpha hCG was observed thereafter. Except for values obtained in very early pregnancy, the beta hCG to hCG ratio remained remarkably constant at approximately 0.5% throughout gestation. In contrast, choriocarcinoma was distinguished by absolute serum beta hCG concentrations 3-100 times greater than the maximum values observed during pregnancy and, more importantly, by exceedingly high beta hCG to hCG ratios. For comparison, we studied hCG, alpha hCG, and beta hCG levels in an additional 178 patients with nontrophoblastic tumors. Ectopic production of alpha hCG and beta hCG was rare (3%), and thus far, we have been unable to demonstrate the presence of hCG in such patients. Therefore, hCG and the free subunits appear not to be useful as serological markers for nontrophoblastic tumors.

Adolescent↗
PubMed1987

Expression of the growth hormone variant gene in human placenta.

Besides the hGH-N gene, which codes for the pituitary 22 and 20K GH variants, the human genome contains a second GH gene, namely the GH-V, which has been thought to be silent. We recently discovered a placental variant of human growth hormone (hPGH), which appears in maternal serum at mid-pregnancy and which rises in concentration thereafter to term. As hPGH and GH-V proteins display very similar characteristics, including a high affinity for hepatic GH receptors, they could be identical. To verify this hypothesis, we sought hGH-V mRNA in placenta. Hybridization experiments were performed between dot-blotted mRNA originating either from placenta or from one pituitary hGH secreting adenoma and synthetic polynucleotide probes corresponding to specific portions of the hGH-V or hGH-N gene sequences. The results indicate that the V gene is indeed expressed in the placenta and, at a very low level, in the pituitary adenoma. Therefore hPGH is most likely the expression product of the hGH-V gene.

Adenoma↗
PubMed1987

[22K and 20K growth hormone: correlation of receptor binding and the biological effect on rat adipocytes].

The 20K variant of native (22K) hGH is a full agonist for the growth promoting and lactogenic properties of the hormone in vivo, but has been reported to have reduced or no insulin-like properties. To explore whether these differences could be explained at the receptor level, we compared the binding of 22K and 20K hGH to receptors in isolated rat adipocytes, a target for the insulin-like effects of the hormone. We compared then the biological insulin-like effects of both hormones using a sensitive assay based on the stimulation of lipogenesis in isolated rat adipocytes. The 20K variant was only 3% as potent as 22K hGH for binding and bioactivity, demonstrating that rat adipocyte receptors are different from those promoting the growth effect.

Adipose Tissue↗
PubMed1987

[Discovery of a placental variant of human growth hormone: biochemistry, physiology and implication in the secretion of hypophyseal forms].

Using two monoclonal antibodies (Mabs), each specific of two distinct hGH epitopes, we evidenced a decrease in serum 22K hGH in pregnant women and increasing levels of a GH-related factor, different from hPL. This factor was extracted from the placenta and partially characterized. Because of its binding to GH hepatic receptors with at least the potency of 22K hGH, it was named human placental growth hormone (hPGH). This hormone alone or together with hPL could therefore take over the role of the lacking pituitary GH in the mother during the last half of pregnancy.

Female↗
PubMed1987

[Influence of placental protein hormones on maternal physiology].

Our data have demonstrated that maternal LH and FSH are repressed throughout pregnancy. Beside, we have discovered and characterized a variant placental GH. Our studies on the mechanism of anovulation and on pituitary GH suppression and GH physiology in pregnant women have contributed to demonstrate the autonomy of the fetoplacental unit and its effects on maternal anabolism and physiology. More specifically, human placental GH, coded by the GH-V gene appears responsible for the anabolic and somatotropic effects mediated by SM-C in the mother. The beneficial aspect of this mechanism for the species appears likely since placental tissues in which the GH-PL genes are deleted, express alternative gene(s) resulting in the production of a placental variant closely related or identical to pituitary 22K GH.

Chromosome Deletion↗
PubMed1986

The receptor binding properties of the 20K variant of human growth hormone explain its discrepant insulin-like and growth promoting activities.

The 20K variant of native (22K) hGH is a full agonist for the growth promoting and lactogenic properties of the hormone in vivo but has been reported to have weak or absent insulin-like properties. To explore if these differences may be explained at the receptor level, we compared the ability of 22K and 20K hGH to inhibit the binding of 125I-22K hGH to receptors in isolated rat adipocytes, a target for the insulin-like effects of the hormone and in IM-9 cultured human lymphocytes, more specific for growth effects. Our data show that while 20K hGH is a potent agonist of native 22K hGH in the IM-9 lymphocyte assay, its potency in the rat adipocyte binding assay is only 3%, even when both cells are incubated together in identical conditions. Thus, the receptors for hGH appear to be different on various target cells, explaining why the 20K variant has different relative biological potencies at different sites of action.

Adipose Tissue↗
PubMed1986

In vitro studies on the Fc-receptor function of mononuclear phagocytes in rheumatoid arthritis: relation between the Fc-receptor blockade and the concanavalin A-binding capacity of autologous immunoglobulin G.

The Fc-receptor (Fc-R) function of monocytes isolated from 19 control subjects and from 30 patients presenting with a rheumatoid arthritis (RA) was assessed in vitro by a classical rosette assay using IgG-coated sheep red blood cells. In RA patients, the percentage of monocytes forming rosettes was significantly lower than in controls (34.4 +/- 20.4 versus 67.4 +/- 4.5%; P less than 0.001). The blockade observed was reversed by a prior trypsin treatment of RA monocytes, the percentage of recovery being correlated with the IgG plasma levels. Besides, IgG purified from the serum of four RA patients bound a mean of 7.3, 5.2, 1.6, and 1.6 times more than normal IgG did onto concanavalin A (Con A), peanut agglutinin (PNA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM), respectively. Although similar amounts of 125I-labeled normal and RA IgG were bound to normal monocytes, RA IgG inhibited more efficiently than normal IgG the Fc-R function of normal monocytes, for all concentrations tested (10 to 100 micrograms/100 microliters). A prior treatment of RA IgG by alpha-mannosidase, but not by beta-galactosidase, significantly reduced their inhibitory properties. The incubation of monocytes with D-mannose or mannan reduced their capacity to form rosettes. The percentage of monocytes forming rosettes in the presence of both mannan and normal IgG was significantly lower than that measured in the presence of normal IgG only. On the contrary, the rosetting capacity of monocytes in the presence of both RA IgG and mannan was the same as that calculated in the presence of RA IgG only. The inhibitory effect of RA IgG was not related to their abnormal circular dichroism. Our data suggest that the greater ability of RA IgG to block the Fc-R function of monocytes probably depends on the presence of a greater number of accessible mannosyl residues on the glycosidic side chains located in the Fc domain of the molecules.

Adult↗
PubMed1986

Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Role of the Fc-binding capacity of protein A in the side effects and the tumoricidal response.

Plasma of twelve patients presenting with a metastic mammary adenocarcinoma was perfused ex vivo over columns of protein A covalently linked to crystalline silica. The plasma of seven patients (group A) was perfused over columns of protein A exhibiting a normal Fc-binding capacity and the plasma of five (group B) over columns of protein A in which the Fc-binding capacity was destroyed. In group A, all patients experienced acute, easily manageable, side effects (hypotension, chills, mild fever, leucocytosis and pain in tumour sites) during or immediately after the immunoadsorption procedures, and three exhibited an objective partial regression after two to five sessions. In contrast, none of the patients from group B developed any acute side effects and all showed evident progression of their disease during the treatment. Tumour cells in all stages of destruction, sometimes surrounded by extensive fibrosis, were seen in biopsies of patients A. However, focal areas of active tumour proliferation were always present in these patients. These data confirm that ex vivo perfusion over protein A columns of plasma from patients with cancer can induce a tumoricidal response in some instances and show that the Fc-binding capacity of protein A is most probably responsible for the necrolytic response and the side effects.

Adenocarcinoma↗
PubMed1986

Early normalization of luteinizing hormone pulsatility after successful transsphenoidal surgery in women with microprolactinomas.

In eight hyperprolactinemic amenorrheic women who had a microprolactinoma, LH secretion was examined by measuring its concentration in blood samples collected every 15 min for 6 h before and 8 days after successful selective adenomectomy. Computer analysis was used for LH peak evaluation. In both circumstances, serum PRL and basal estradiol (E2) levels were also determined. Before operation, the number of LH peaks ranged from zero to one per 6 h in seven patients and was two per 6 h in the eighth patient. In all patients, serum PRL was normal on the eighth postoperative day, while E2 levels remained low, similar to the values usually found in the early follicular phase of the cycle in normal women. Postoperatively, mean LH levels were similar to preoperative levels, but there was a dramatic increase in the number of LH peaks (three to five per 6 h) in five of the eight patients. These observations confirm the impairment of LH pulsatility in hyperprolactinemia and demonstrate that normalization of PRL levels by surgery can restore LH pulsatile secretion in certain women as early as the eighth day after operation in the absence of a significant change in serum E2 levels. Thus, the preoperative impaired pulsatility of LH secretion was probably a central effect of hyperprolactinemia.

Adenoma↗
PubMed1986

Ontogeny of hypothalamic pituitary function in the pig: pituitary thyrotrophin in the fetus and neonate.

Thyrotrophin in individual pituitaries obtained from fetal and prepubertal pigs was quantified by homologous radioimmunoassay (RIA) and heterologous radioreceptor assay (RRA). Relative evolution of pituitary TSH contents and concentrations with age were in good agreement as measured by both assay systems although the quantity of TSH detected by RRA appeared consistently lower than that measured by RIA. Thyrotrophin was first detected in pituitaries of fetal pigs at day 75 of gestation. Thereafter the pituitary content of TSH increased to approximately 45 micrograms/pituitary in the oldest group tested (6 weeks of age). The pituitary TSH concentration rose sharply until birth (114 +/- 1 day post coitum) and thereafter remained increased at a concentration of approximately 400 ng/mg wet weight.

Animals↗
PubMed1986

Developmental changes in gonadotrophins and testicular gonadotrophin receptors in the pig, from neonatal to adult life.

Changes in the concentrations of LH and FSH testicular receptors have been studied in the pig, from neonatal to adult life, and correlated with blood LH, FSH and testosterone concentrations. Quantification of gonadotrophin receptors was performed in equilibrium binding studies, using homologous systems. The presence of high-affinity binding sites for LH and FSH (association constant (Ka): LH approximately 20 litres/nmol; FSH approximately 10 litres/nmol) was demonstrated in the testes of all animals studied. The apparent affinity of LH and FSH receptors did not change significantly with age. During the first weeks of life, there was a transient rise in LH receptor content, reaching a maximum of 8.7 +/- 2.2 (mean +/- S.E.M.) pmol/g testis at 24 days of age. This was correlated with a peak in testosterone secretion and reflects the second wave of interstitial cell proliferation in the pig. A second increase in the number of LH receptors occurred after 12 weeks of age and corresponds to pubertal maturation and final differentiation of adult Leydig cells. During this period, circulating concentrations of testosterone markedly increased without any significant variation in LH blood levels, suggesting a change in testicular sensitivity to LH in the maturing pig. A continuous increase in FSH receptor content was observed from the neonatal to the adult pig. This increase occurred in two phases. During the first 2 months of life, the increase in the number of FSH receptors exceeded that of testis growth rate and resulted in an increase in FSH receptor concentrations which reached a peak at 12.1 +/- 1.8 pmol/g testis, at week 9.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Thyroiditis].

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Adult↗