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Biomedical subjects

R Guillemin

Publications and source records attributed to R Guillemin.

At least 91 records · Page 5Linked to original sources
PubMed1983

A noninvasive functional lesion of the hypothalamo-pituitary axis for the study of growth hormone-releasing factor.

Rats were passively immunized with an antiserum against somatostatin and a monoclonal antibody against rat hypothalamic growth hormone-releasing factor (rGRF-mAb) which does not recognize the biologically active 1-40 amino acid fragment of hpGRF-44 (hpGRF-40). Using this paradigm we have observed that the pituitary possesses a resilient capacity to release growth hormone (GH) following repeated injections of hpGRF-40 and that this response follows a dose-dependent relationship.

Animals↗
PubMed1983

Synthetic human pancreas growth hormone-releasing factor (hpGRF1-44-NH2) stimulates growth hormone secretion in normal men.

A synthetic replicate of human pancreas growth hormone-releasing factor, hpGRF1-44-NH2, (hpGRF44), a 44-amino acid amidated peptide, was administered to seven normal men. In addition to placebo, 4 subjects received 3 doses of hpGRF44 (0.5 microgram/kg, 5 micrograms/kg, 10 micrograms/kg), while one subject received 2 doses (5 micrograms/kg, 10 micrograms/kg) and 2 subjects received one dose (0.5 microgram/kg or 5 micrograms/kg), each as a rapid intravenous injection. A significant increase in circulating growth hormone (GH) was observed at each dose (0.5 microgram/kg, p = 0.05; 5 micrograms/kg, p less than 0.005; 10 micrograms/kg, p = 0.01) when compared to placebo, with equivalent maximal responses. At all doses studied a rise in plasma GH occurred within 5 min, with a peak response in most patients at 30-45 min. There were no associated changes in any of the other anterior pituitary hormones or insulin. Other than transient flushing and minimal changes in vital signs, no side effects were noted. The results of these studies support the potential usefulness of hpGRF44 for the assessment of GH secretion and reserve, and of this peptide or an analog as a therapeutic agent to stimulate GH release.

Adult↗
PubMed1983

[Acromegaly, clinical expression of the production of growth hormone releasing factor in pancreatic tumors].

In exceptional cases, acromegaly develops as the clinical expression of an ectopic secretion of Growth Hormone (GH) or Growth Hormone-Releasing Factor (GRF), tumorous in origin. In the present report, we describe an instance of acromegaly caused by the secretion of GRF from a voluminous pancreatic tumor. The resection of this tumor resulted in a temporary disappearance of the biological and clinical symptoms of acromegaly, which then reappeared in conjunction with a rise in plasma GRF. From this pancreatic tumor, substances displaying a potent GRF activity were isolated and characterized. Amino acid analyses revealed that they were related to 3 peptides containing respectively 44, 40 and 37 aminoacids. The largest (hp GRF (1-44)-NH2) referred as hp GRF or somatocrinin is considered to be the primary molecule. The pancreatic tumor was multisecreting as proved by high plasma levels of somatostatin, pancreatic polypeptide and glucagon, normalized after the tumor removal, taken together with the immunocytochemical demonstration of the presence of these peptides in the tissue and with the isolation of somatostatin. In contrast hypercalcemia associated with an elevated plasma level of IR-PTH was unmodified by tumor removal. Diagnosis of acromegaly as ectopic endocrine syndrome will probably be facilitated by plasma GRF radioimmunoassay, as a result of production of anti synthetic GRF antibodies.

Acromegaly↗
PubMed1982

[Somatomedin inhibition of the growth hormone secretion stimulated by the hypothalamic factor somatocrinin or the synthetic peptide hpGRF].

In the in vitro monolayer pituitary cell culture system somatomedin-C and IGF-I are practically equipotent to inhibit the secretion of growth hormone stimulated by hypothalamic growth hormone releasing factor (GRF) or the synthetic peptide hpGRF-44 (3-200 x 10(-12)M). Highly purified somatomedin-C or IGF-I are active to inhibit the effect of GRF at concentrations of 0.5 to 10 ng/ml(1.0 x 10(-10) M - 1.3 x 10(-9) M) in either short-term (3-4 hrs.) or long-term (24 hrs.) incubation, with no statistical difference between the results obtained in either duration of incubation. IGF-II is less potent than IGF-I as an inhibitor of GRF. The effect of the somatomedins is specific for the secretion of growth hormone and is not duplicated by other growth factors such as epidermal growth factor (EGF) or fibroblast growth factor (FGF).

Animals↗
PubMed1982

Monoclonal antibodies to hypothalamic growth hormone-releasing factor with picomoles of antigen.

Monoclonal antibodies specific for rat hypothalamic growth hormone-releasing factor (rGRF) have been produced by in vitro immunization of mouse spleen cells with less than 1 nanomole of rGRF in a partially purified preparation. Hybridoma supernatants were screened for anti-rGRF activity by use of a pituitary culture assay system that can detect growth hormone-releasing factor in the femtomole range. Such highly sensitive in vitro techniques permit the use of picomole quantities of an antigen in partially purified preparations for the isolation of monoclonal antibodies, which can in turn be used in biological studies and in immunochemical procedures for large-scale purification and isolation of that antigen.

Animals↗
PubMed1982

Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly.

A 44 amino acid peptide with growth hormone-releasing activity has been isolated from a human tumor of the pancreas that had caused acromegaly. The primary structure of the tumor-derived peptide is H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala- Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly -Ala-Arg-Ala-Arg-Leu-NH2. The synthetic replicate has full biological activity in vitro and in vivo specifically to stimulate the secretion of immunoreactive growth hormone. The tumor-derived peptide is identical in biological activity and similar in physiochemical properties to the still uncharacterized growth hormone-releasing factor present in extracts of hypothalamic tissues.

Acromegaly↗
PubMed1982

Growth hormone releasing factor, somatocrinin, releases pituitary growth hormone in vitro.

Purified (rat) hypothalamic growth hormone releasing factor (GRF), native human GRF isolated from an islet cell tumor of the pancreas that had caused acromegaly, and the synthetic replicates of the human material are potent secretagogues of immunoreactive growth hormone (GH) by primary cultures of rat pituitary cells. Native or synthetic peptides give identical dose-response curves, with identical slopes and identical maximal effects. The median effective dose of the tumor-derived GRF is 15 x 10(-12) M. The effect of hypothalamic GRF or of a synthetic replicate of tumor-derived GRF is immediate, being demonstrable in less than or equal to 30 sec after contact in a pituitary cell perifusion system. The effect of hypothalamic GRF or of tumor-derived GRF is highly specific for stimulating release of immunoreactive growth hormone; there is no demonstrable concomitant effect on the secretion of other pituitary hormones. Somatostatin-28 and somatostatin-14 inhibit the release of growth hormone produced by hypothalamic GRF or tumor-derived GRF in typical noncompetitive antagonism. On the basis of the results reported here, hypothalamic GRF and tumor-derived GRF are qualitatively indistinguishable in their ability to stimulate the secretion of immunoreactive growth hormone in vitro. The name "somatocrinin" is proposed to replace the acronym GRF.

Amino Acid Sequence↗
PubMed1982

Presence of somatostatin-28-(1-12) in hypothalamus and pancreas.

Acid extracts from rat pancreas and hypothalamus were analyzed for the presence of the antigenic determinant corresponding to the NH2 terminus of somatostatin-28 (SS28), using an antiserum directed against amino acids 1 to less than or equal to 11 of the SS28 molecule. On gel permeation chromatography the majority of the immunoreactive material from each tissue extract eluted in one zone compatible with a peptide of 1250 daltons. Purification of this immunoreactive material by reverse-phase HPLC and cation-exchange chromatography yielded two immunoreactive peptides from each tissue extract. The amino acid compositions of both peptides in pancreas and hypothalamus correspond to the fragment 1-12 of SS28. The more hydrophobic peptide from each tissue coeluted with synthetic SS28-(1-12) on HPLC, while the other one coeluted with synthetic SS28-(1-12)-amide. We conclude that the prosomatostatin fragment Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-OH is present in both rat hypothalamus and rat pancreas.

Amino Acid Sequence↗
PubMed1982

Molecular forms of the putative enkephalin precursor BAM-12P in bovine adrenal, pituitary, and hypothalamus.

A highly specific radioimmunoassay for one of the putative adrenomedullary [Met]enkephalin precursors, BAM-12P (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu-OH), has been developed. The BAM-12P antibodies recognize the COOH-terminal fragment of the peptide from Arg7 to Glu12 and do not crossreact with [Met5]- or [Leu5]enkephalin or any of their COOH-terminal lysine or arginine extended analogs. Specificity for the COOH-terminal Glu-OH is suggested by the 100% crossreactivity with BAM-12P5-12 and 0.3% crossreactivity with BAM-12P5-12 amide. Using these antibodies, we have measured three forms of BAM-12P-like immunoreactivity in extracts of bovine adrenal medulla, of which the major form (greater than 90%) corresponds to BAM-12P by molecular weight. Extracts of bovine adrenal cortex contain 1% the amount of a BAM-12P-like material (Mr approximately 1400; 20 ng per gland), possibly due to crosscontamination with adrenomedullary tissue. The major form of BAM-12P-like material in extracts of bovine neurointermediate pituitaries is of higher molecular weight than authentic BAM-12P (Mr approximately 4000); the remaining material (10%) corresponds to BAM-12P by molecular weight. There is no detectable BAM-12P-like immunoreactivity in crude or purified extracts of bovine anterior pituitaries. Extracts of bovine hypothalamic tissues contain small amounts of BAM-12P immunoreactivity (approximately 2 ng per fragment) which can be detected as one molecular form corresponding to a 1400-dalton molecule. The results indicate that the enkephalin precursor found in the adrenal medulla also may be present in the pituitary and hypothalamus. Furthermore, the processing of this molecule appears to be tissue-specific.

Adrenal Cortex↗
PubMed1982

Somatostatin-28(1-12)-like immunoreactivity in the rat.

The distribution of the newly characterized peptide somatostatin-28(1-12) was determined in rat tissues using a radioimmunoassay in which the immune plasma is directed against the C-terminus of the dodecapeptide. In the central nervous system, somatostatin-28(1-12)-like immunoreactivity is highly concentrated in the hypothalamus and the amygdala. In the digestive system, the highest levels of immunoreactivity are found in the stomach, the pancreas and the colon. The immunoreactive material measured in different tissues is the heterogenous: in addition to the dodecapeptide, two N-terminally extended somatostatin-28(1-12) peptides of 4,400 and 8,000 mol wt are also detected by the immune plasma. However, the dodecapeptide itself usually accounts for the majority (66 to 75%) of the total somatostatin-28(1-12)-like immunoreactivity present in those tissues.

Animals↗