Growth hormone releasing factors.
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Adenoma, Islet Cell↗
Biomedical subjects
A Baird
Publications and source records attributed to A Baird.
Physiological studies with somatocrinin, a growth hormone-releasing factor.
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Animals↗
Immunoreactive and biologically active growth hormone-releasing factor in the rat placenta.
Rat placentas from fetuses of 18 and 20 days of gestation were collected, extracted, and examined for their capacity to stimulate GH release in vitro. The crude extract stimulated, in a dose-dependent fashion, GH release by rat anterior pituitary cells in monolayer culture. The biological and immunological activities retained on antirat GH-releasing factor immunoaffinity columns eluted on Sephadex G-75 (fine) columns with an estimated mol wt of 5000 daltons. Reverse phase HPLC of this material revealed the presence of two forms of GRF activity that eluted with retention times identical to those of synthetic rat GRF and its methionine sulfoxide counterpart [Met(O)27]GRF. The results demonstrate the presence of an immunoreactive and biologically active GRF in the rat placenta that is indistinguishable from rat hypothalamic GRF.
Animals↗
Corpus luteum angiogenic factor is related to fibroblast growth factor.
An angiogenic growth factor present in bovine corpus luteum (CL) has been purified to apparent homogeneity by a combination of differential salt precipitation, ion exchange chromatography, and heparin-Sepharose chromatography. It is a single chain polypeptide with an apparent mol wt of 15,000 and an amino acid composition similar to that previously reported for pituitary and brain fibroblast growth factor (FGF). Sequence analysis of the first 17 residues of the CL-derived growth factor identified the sequence; His-Phe-Lys-Asp-Pro-Lys-Arg-Leu-Tyr-X-Lys-Asn-Gly-Gly-X-Phe-Leu. This sequence is identical to residues 16-33 of bovine pituitary and brain FGF, indicating that the CL-derived growth factor is an amino-terminally truncated form of FGF and is otherwise similar, if not identical, to FGF. The biological activity of CL FGF is indistinguishable from that of pituitary or brain FGF. It is highly active in triggering the proliferation of cultured bovine vascular endothelial cells derived either from large vessels (aortic arch) or from corpus luteum and adrenal cortex capillaries (half-maximal stimulation at 20-40 pg/ml and saturation at 400-600 pg/ml). In vivo implants containing 50 ng to 1 microgram CL-derived growth factor stimulate neovascularization in the chorioallantoic membrane of the chick embryo. In addition to being mitogenic for vascular endothelial cells, CL FGF also stimulates the proliferation of a wide variety of mesoderm- and neuroectoderm-derived cells, including vascular smooth muscle cells, granulosa and adrenal cortex cells, rabbit costal chondrocytes, and corneal endothelial cells.
Allantois↗
Lung tissue penetration of temocillin.
Eight patients about to have the whole or part of a lung resected were given a 2g bolus dose of temocillin. A series of serum samples and a piece of peripheral lung tissue were collected and assayed for temocillin concentration. 30 minutes after drug administration, the mean serum and tissue concentrations were 172 mg/L and 45 mg/kg respectively.
Adult↗
Temocillin in the treatment of chest infections.
In our study, 16 patients with acute infection complicating severe respiratory disease were treated with temocillin 2g or 3g daily for 5 to 10 days. In 10 patients, a recognised respiratory pathogen, either Haemophilus influenzae (temocillin-sensitive) or Streptococcus pneumoniae (temocillin-resistant), was isolated from sputum before the start of treatment. 13 patients improved clinically but 5 subsequently relapsed. Two patients failed to respond, and 1 died of respiratory failure. There was no clearcut relationship between the clinical progress and sensitivity of the isolated pathogen to temocillin, and there were no adverse effects associated with the administration of temocillin.
Aged↗
Synthesis and in vitro bioactivity of C-terminal deleted analogs of human growth hormone-releasing factor.
A series of C-terminal deleted analogs of human growth hormone-releasing factor (hGRF) with either an amidated or a free carboxylic acid C-terminus were synthesized by solid phase methodology. Their capacity to release growth hormone was tested on rat anterior pituitary cells in monolayer culture. A gradual decrease of bioactivity down to 23% relative to hGRF was noted when the C-terminal amino acids were deleted to hGRF (1-34)OH. Further deletions, however, did not decrease the bioactivity because the potencies of the fragments, hGRF(1-31)NH2, (1-30)NH2 and (1-29)NH2 remained at about 50% of that of hGRF. Continual deletion of residues to hGRF(1-23)NH2, (1-22)NH2 and (1-21)NH2 still yielded bioactive fragments with full intrinsic activity despite very low potency. Only with the deletion down to hGRF(1-19)NH2 did the bioactivity completely disappear. Thus, together with the data published in a previous paper (1), the minimal biologically active core of hGRF with full intrinsic activity comprises the fragment (3-21).
Animals↗
Isolation and characterization of the bovine hypothalamic corticotropin-releasing factor.
A 41 amino acid peptide with high intrinsic corticotropin-releasing activity was isolated from 1000 bovine hypothalami by means of immunoaffinity chromatography, gel filtration, and two steps of reverse phase HPLC. The primary structure of the amino terminal 39 amino acids was characterized by gas phase sequence analysis. The sequence of the amidated carboxyl terminal dipeptide was established by digestion of the intact natural product with Staphylococcus aureus V8 protease, dansylation of the digest and comparative reverse phase liquid chromatography studies with the synthetic dansylated dipeptides Ile-Ala-NH2, Ile-Ala-OH, Ala-Ile-NH2 and Ala-Ile-OH. The complete structure of the bovine corticotropin-releasing factor was established as: Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val- Leu- Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Asn-Asn-Arg-Lys-Leu- Leu- Asp-Ile-Ala-NH2 using approximately 650 pmol of material.
Amino Acid Sequence↗
Isolation and characterization of caprine corticotropin-releasing factor.
The hypophysiotropic peptide, corticotropin-releasing factor (CRF) was isolated from caprine hypothalamic median eminence tissue by means of acid extraction, immunoaffinity chromatography, gel filtration and two steps of reverse-phase high-performance liquid chromatography (RPLC). Amino acid sequence determination using a gas-phase sequencer established the primary structure of the first 39 residues from the NH2-terminus. The nature of the COOH-terminal dipeptide was elucidated by Staphylococcus aureus V8 protease digestion of the native peptide, dansylation of the digest and comparative RPLC studies with the dansylated dipeptides Ile-Ala-NH2, Ile-Ala-OH, Ala-Ile-NH2 and Ala-Ile-OH. The complete structure of the peptide was established as: H-Ser-Gln-Glu-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu- Val-Leu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-Leu-Leu-Asp-Ile-Ala-NH2, which is identical to that of ovine CRF.
Amino Acid Sequence↗
Synthesis and in vitro bioactivity of human growth hormone-releasing factor analogs substituted at position-1.
Eight position-1 analogs of the 40-amino acid fragment and two position-1 analogs of human growth hormone-releasing factor were synthesized by solid phase methodology and their capacity to release growth hormone was determined using rat anterior pituitary cells in monolayer culture. Relative to hGRF(1-40)OH, which was arbitrarily assigned a potency value of 1, [D-Tyr1]hGRF(1-40)OH, [Phe1]hGRF(1-40)OH, [Trp1]hGRF(1-40)OH, [His1]hGRF(1-40)OH, [Ala1]hGRF(1-40)OH, [(-Ac)Tyr1]hGRF(1-40)OH, Arg0-hGRF(1-40)OH and Ala0-hGRF(1-40)OH have potencies of 0.022, 0.038, 0.003, 0.351, 0.010, 0.032, 0.002 and 0.007 respectively. Relative to hGRF(1-44)NH2 = 1, [(3-Me)His1]hGRF(1-44)NH2 and [(O-Me)Tyr1]hGRF(1-44)NH2 have potencies of 0.132 and 0.001 respectively. These results demonstrate the prerequisite for an aromatic residue at position-1 for potent biological activity and also suggest that the capacity for hydrogen bond formation with the first residue is required for full receptor-ligand interaction.
Amino Acids↗
Detection of the messenger RNA coding for preproenkephalin A in bovine adrenal by in situ hybridization.
The messenger RNA (mRNA) coding for the adrenal precursor of enkephalins (preproenkephalin-A) has been detected in bovine adrenal medulla cells using in situ hybridization with 32P-labelled preproenkephalin A (PPA) complementary DNA. In formaldehyde- and Carnoy-fixed tissue sections, an intense elective labelling restricted to the cells located at the periphery of the adrenal medulla can be detected after hybridization procedure, using X-ray film and classical autoradiographic procedure. Adequate controls show that this labelling is obtained only using PPA complementary DNA, inserted or not in its vector. Distribution of PPA mRNA appears identical to that of its immunoreactive end products, namely Met-enkephalin and BAM22 peptide, detected by immunohistochemistry. Norepinephrine, detectable using monoamine histofluorescence, appears restricted to the cells of the center of the gland unlabelled for PPA mRNA and its end-products. Cultured bovine adrenomedullary cells that exhibited enkephalin immunoreactivity also contain PPA mRNA located in their cytoplasm.
Adrenal Glands↗
Ontogeny of the response to growth hormone-releasing factor.
Primary cell cultures were prepared from fetal, neonatal and adult rat pituitaries and evaluated for their ability to secrete growth hormone (GH) in response to growth hormone-releasing factor (GRF). Pituitary cells prepared from fetuses at days 19 and 21 of gestation, neonatal animals at the day of birth (day 0) or the following day (day 1) and peripubertal male rats showed full dose response curves to GRF with maximal GH release when stimulated with 1 X 10(-10) M rat GRF. At this concentration of GRF, the amount of GH released was not different from that elicited by activation of adenylate cyclase with 1 X 10(-5) M forskolin. In contradistinction, a preparation of cells from fetuses at day 18 of gestation did not show the same release of GH when challenged with 1 X 10(-10) M GRF and forskolin (0.057 +/- 0.001, compared to 0.076 +/- 0.003 micrograms/10(5) cells per 4.5 h), although the cells clearly responded to both secretagogues (basal levels of GH, 0.029 +/- 0.002 micrograms/10(5) cells per 4.5 h). While cells prepared from fetuses at day 21 of gestation or from animals after birth released 5-10% of their total cellular GH content, those prepared from 18- and 19-day fetuses released as much as 40% of their total GH suggesting there is a maturation of intracellular GH processing that occurs late in gestation. The results show that, in late pregnancy, the rat fetal pituitary is highly responsive to growth hormone-releasing factor and suggest that this peptide participates in regulating GH levels during the perinatal period.
Aging↗
Somatocrinin, the growth hormone releasing factor.
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Adenylyl Cyclases↗
Isolation and partial molecular characterization of pituitary fibroblast growth factor.
Fibroblast growth factor (FGF) has been purified to homogeneity from bovine pituitaries by two methods. Starting material for both methods was an FGF preparation partially purified as described by Gospodarowicz [Gospodarowicz, D. (1975) J. Biol. Chem. 250, 2515-2520]. Purification procedure I involved cation-exchange and reversed-phase HPLC, while procedure II employed gel filtration and ion-exchange chromatography. Isolation was monitored by testing column fractions for their capacity to stimulate the proliferation of vascular endothelial cells in vitro. The growth factor has an approximate molecular weight of 16,000. Its amino-terminal sequence was determined as Pro-Ala-Leu-Pro-Glu-Asp-Gly-Gly-Ser-Gly-Ala-Phe-Pro-Pro-Gly. Sequence and amino acid composition indicate that the structure of pituitary FGF is different from that of other known growth factors. Pituitary FGF, as isolated under nonacidic conditions (procedure II), has high potency and intrinsic activity to stimulate adult bovine aortic endothelial cells (half-maximal proliferation at 2 pM). Acidic conditions as in procedure I, however, lead to about 90% loss of potency while the intrinsic activity remains intact (identical maximal stimulation values). By all other criteria (molecular weight, amino acid composition, amino-terminal sequence), the two preparations are indistinguishable. Antibodies were raised in rabbits against a synthetic peptide representing the first nine residues of the amino-terminal sequence of the pituitary FGF. The polyclonal antibodies recognize the synthetic peptide and the purified growth factor on an equimolar basis and are capable of inhibiting mitogenic activity in vitro. This report describes a partial chemical characterization of a pituitary FGF and demonstrates rigorously that the characterized protein possesses the mitogenic activity commonly referred to as "basic pituitary FGF."
Amino Acid Sequence↗
Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor.
Brain and pituitary fibroblast growth factors (FGF) have been purified to apparent homogeneity from crude tissue extracts by a three-step procedure, including salt precipitation, ion-exchange chromatography, and heparin-Sepharose affinity chromatography. Brain and pituitary FGF have similar amino acid compositions and are indistinguishable with respect to molecular weight (16,000 by polyacrylamide gel electrophoresis), retention behavior in reversed-phase high-performance liquid chromatography, and recognition by antibodies directed against the amino-terminal sequence of pituitary FGF. Brain FGF preparations purified by heparin-Sepharose contain, in addition to the major FGF molecular species, at least two additional forms of the growth factor, which appear to be very similar by all the above criteria, except for retention in high-performance liquid chromatography.
Animals↗
Multiple stimulation of the adenohypophysis by combinations of hypothalamic releasing factors.
We have investigated the in vitro and in vivo interactions of the four hypothalamic releasing factors, LHRH, corticotropin-releasing factor, TRH, and GH-releasing factor on anterior pituitary hormone secretions, using a 2 X 2 X 2 X 2 factorial experimental design. This experimental design allows for the evaluation of both the main treatment effects of the hypothalamic releasing factors as well as all of the possible interactions between them. Significant main treatment effects were: LHRH on LH and FSH, corticotropin-releasing factor on ACTH and beta-endorphin, TRH on TSH, and GH-releasing factor on GH. These results confirm the specificity of the four releasing factors on their respective target cells. There were no significant interactions between any of the releasing factors on anterior pituitary hormone secretions. These results suggest that the changes in pituitary secretion that are observed under physiological conditions are not due to interactions between the hypothalamic releasing factors at the level of the pituitary, but rather to other secondary interactions that modify pituitary activation or response. These results also indicate that the clinical pituitary reserve tests can be expanded to include all four hypothalamic releasing factors, since any lack of response will reflect a specific pituitary defect and not a failure to respond owing to interaction of the secretagogues administered.
Adrenocorticotropic Hormone↗
In vitro and in vivo evidence that the C-terminus of preproenkephalin-A circulates as an 8500-dalton molecule.
One of the major immunoreactive components of the enkephalin precursor BAM-22P in extracts of adrenal medulla is a molecule of approximately 8500 Da. A similar component is detected, after gel-permeation chromatography, in extracts of bovine plasma and in culture medium harvested from acetylcholine-stimulated bovine adrenomedullary cells in culture. Simultaneous detection of the C-terminal epitome of preproenkephalin-A: Met-enkephalin-Arg6-Phe7-OH in this secreted high-molecular-weight zone suggest that the approximately 8500-Da form of BAM-22P is the C-terminal of preproenkephalin A.
Adrenal Medulla↗
Potent interaction between glucocorticoids and growth hormone-releasing factor in vivo.
Administration of dexamethasone significantly enhanced the pituitary growth hormone response to growth hormone-releasing factor in intact as well as adrenalectomized rats. Thus the inhibitory effects of glucocorticosteroids on somatic growth which involve an interaction of these steroids and growth hormone at a peripheral level may also involve a modification of pathways within the central nervous system that regulate normal growth hormone secretion.
Adrenalectomy↗