159 results match your criteria: "Whittier Institute for Diabetes and Endocrinology; La Jolla[Affiliation]"
Clin Obstet Gynecol
September 1990
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Based on the extensive amount of research on inhibin and related polypeptides accomplished during the past 5 years, the inhibin concept put forth more than 50 years ago has not only become well established but also more complex than originally imagined. The closed-loop feedback mechanism of ovarian inhibin and pituitary FSH has been joined by possible "inhibin-like" actions of follistatin and FSH-stimulatory effects of activin. In addition, in vitro experiments suggest possible autocrine and paracrine functions for the gonadal polypeptide hormones.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
August 1990
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
The receptor-binding properties of monomeric nonglycosylated human PRL (hPRL), glycosylated hPRL that does not bind to Concanavalin-A-Sepharose (G1-hPRL) and glycosylated hPRL that binds to Concanavalin-A-Sepharose (G2-hPRL) were tested in the lactating rabbit mammary gland RRA for lactogenic hormones. Variations in the glycosylation pattern of G-hPRL altered its receptor-binding properties, suggesting that the site of glycosylation may be proximal to the receptor-binding region. Relative potencies for the displacement of [125I]hPRL by hPRL, G1-hPRL, and G2-hPRL were 100%, 40%, and 26%, respectively.
View Article and Find Full Text PDFEndocrinology
July 1990
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California 92037.
The concentrations of glycosylated (G-PRL) and nonglycosylated (non-G-PRL) forms of PRL and GH were measured during pregnancy in pigs of lean and obese (high backfat thickness) lines. Pregnant sows of the two genetic lines were killed, in groups of five to eight, at 60, 75, 90, and 105 days of gestation, and their pituitary glands and plasma were analyzed for the two hormones by immunoblotting, lectin-binding, and RIA techniques. In both lean and obese pigs, pituitary concentrations of G-PRL and non-G-PRL increased with advance in pregnancy, but there were no significant changes in either form of pituitary GH.
View Article and Find Full Text PDFEndocrinology
April 1990
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
The effects of insulin-like growth factor binding proteins (IGF-BPs) purified from porcine follicular fluid on granulosa cell function were examined using serum-free cultures of rat granulosa cells obtained from immature, diethylstilbestrol-treated rats. Both the so-called GH-dependent (IGF-BP3) and non-GH-dependent (IGF-BP2) proteins dose dependently inhibited granulosa cell estradiol and progesterone production with IC50s of 4.1-7.
View Article and Find Full Text PDFJ Cell Biol
March 1990
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Immunohistochemical methods were used to study the distribution of basic FGF in the 18-d rat fetus. The results reveal a pattern of widespread yet specific staining that is consistent with the wide distribution of basic FGF. Immunoreactive basic FGF is associated with mesenchymal structures, mesoderm- and neuroectoderm-derived cells, and their extracellular matrices.
View Article and Find Full Text PDFBiochem Biophys Res Commun
February 1990
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Analogs of human and rat growth hormone-releasing factor (hGRF and rGRF), related to [D-Arg2]hGRF(1-29)NH2, were synthesized by solid phase methodology. Their capacity to inhibit growth hormone secretion stimulated by hGRF(1-44)NH2 was tested on rat anterior pituitary cells in monolayer culture. Among the analogs of hGRF, [D-Arg2,29,Arg30]hGRF(1-30)NH2 showed the highest antagonistic potency of 3.
View Article and Find Full Text PDFJ Biol Chem
February 1990
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Recently, an inhibitory polypeptide that could block the follicle-stimulating hormone-induced estradiol and progesterone production in rat ovary granulosa cells has been isolated from porcine ovarian follicular fluid. Amino-terminal sequence analysis of the purified inhibitor suggests that it could be the porcine congener of the 53-kDa subunit of the growth hormone-dependent insulin-like growth factor binding protein (IGF-BP3). Using amino acid sequence information derived from the purified inhibitor to construct oligonucleotide probes, we have now identified the complementary deoxyribonucleic acids (cDNAs) encoding the inhibitory polypeptide from a porcine liver and a porcine ovary library.
View Article and Find Full Text PDFPancreas
January 1990
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
In order to study the possible differential effects of the nonglycosylated and glycosylated forms of prolactin on insulin content and secretion in pancreatic islets, neonatal rat pancreatic islets were exposed for 6 days in vitro to 2 micrograms/ml of nonglycosylated ovine prolactin (oPRL), or to 2 micrograms/ml of glycosylated oPRL (G-oPRL). oPRL stimulated a significant increase (p less than 0.01) in the total amount of insulin released into the medium over the 6 day culture period; however, G-oPRL had no effect.
View Article and Find Full Text PDFProg Growth Factor Res
March 1992
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
When the selective specificity and exquisite affinity of growth factors for their receptors is conferred to protein toxins, the chimeric molecules so generated become potent cytotoxins. Chimera are produced by the chemical conjugation of the two proteins or by expression of fusion proteins in bacterial expression systems. The toxic moiety, usually a ribosome-inactivating protein or a fragment of a bacterial toxin, is internalized into target cells by receptor-mediated endocytosis.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 1989
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Insulin-like growth factors (IGFs) found in extracellular fluids are bound to specific binding proteins. Recently a high molecular weight IGF-binding protein (IGF-BP3) has been isolated from porcine ovarian follicular fluid based on its inhibition of follicle stimulating hormone-stimulated estradiol production in rat granulosa cells. The complete primary structure of the porcine IGF-BP3 was deduced by molecular cloning.
View Article and Find Full Text PDFHorm Metab Res
December 1989
Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California.
We measured glycosylated PRL (G-PRL) in the pituitary gland and plasma of lean and obese barrows (castrated male pigs) by immunoblotting. We found that G-PRL constituted 40% or more of total monomeric PRL in the pituitary gland of these animals. Furthermore, pituitary G-PRL concentrations in obese barrows averaged 58% higher than in those of lean controls.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 1989
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Using gel filtration, ligand-affinity chromatography and reversed phase HPLC, four insulin-like growth factor-binding proteins (IGF-BPs) have been purified from adult rat serum. Sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis revealed that all four proteins migrated as doublets at 45/37 (peak 1 in Fig.4), 36/32 (peaks 2 and 5 in Fig.
View Article and Find Full Text PDFProc Soc Exp Biol Med
September 1989
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California 92037.
The amino-terminal portion of human growth hormone, residues 1-43 (hGH1-43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human growth hormone (hGH), is antagonistic to the action of insulin. The effects of hGH, hGH1-43, and HP on glucose metabolism were assessed in young (4-5 weeks) and adult (6-8 months) hypophysectomized yellow Avy/A mice which lacked any interfering endogenous pituitary hormones, and compared with age-matched intact obese yellow Avy/A and lean agouti A/a mice. Treatment with hGH1-43 or HP did not promote body growth in hypophysectomized yellow mice; but after 2 weeks of treatment with hGH, there was a significant increase in body weight (P less than 0.
View Article and Find Full Text PDFJ Neurosci Res
September 1989
Whittier Institute for Diabetes and Endocrinology, La Jolla, California.
The role of protein tyrosine phosphorylation in the response of PC12 cells to NGF was investigated by using a variety of agents which affect NGF-induced neurite outgrowth. K-252a, a kinase inhibitor, was previously found to selectively inhibit many of the actions of NGF on PC12 cells. In the present study, it was shown to inhibit NGF-induced protein tyrosine phosphorylation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 1989
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, CA 92037.
Recently we identified five novel peptides of Mr 13,000 to 18,000 (designated P13, P14, P16, P17, and P18 according to approximate Mr) in the anterior pituitary gland of rat and man that appeared related to GH and PRL in regulation and structure. We have now raised polyclonal antibodies in the rabbit to four of these peptides--P13, P14, P17 and P18--isolated from rat anterior pituitary; the rabbit injected with P16 did not produce antibodies. Besides reacting with their respective immunogens, antisera to all four peptides crossreacted, quite unexpectedly, with human GH and with human, porcine, and ovine PRL.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 1989
Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Human basic fibroblast growth factor (bFGF) is an angiogenic polypeptide mitogen present in a wide variety of mesoderm- and neuroectoderm-derived tissues. bFGF cDNA and genomic clones predict a 17.8-kDa (155-amino acid) gene product based on the presence of a single putative translational initiator ATG codon.
View Article and Find Full Text PDFProc Soc Exp Biol Med
June 1989
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California 92037.
Insulin-like and anti-insulin effects of human growth hormone (hGH) were examined by determining the effects of two peptides representing portions of the hGH molecule in lean agouti A/a and obese yellow Avy/A and ob/ob mice. The peptides were the amino terminal segment, residue 1-43 (hGH1-43), which has been shown to potentiate the response to insulin and another peptide, hyperglycemic peptide (HP), with unknown structure, which has anti-insulin activity. The anti-insulin component is an acidic low molecular weight peptide which co-purifies with hGH but was not recognized by antibodies to intact hGH and did not cross-react with anti-hGH1-43 antiserum.
View Article and Find Full Text PDFEndocrinology
March 1989
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Two forms of glycosylated PRL (G-PRL) which differed in their binding properties to Concanavalin-A (Con-A) were isolated from human pituitary glands. One form, G1-hPRL, was only slightly retarded by Con-A; the other, G2-hPRL, was adsorbed by Con-A and could be eluted with methyl-D-manno-pyranoside, an indication of differing carbohydrate units in the two G-PRLs. Differences in type of glycosylation were also indicated by HPLC peptide mapping of tryptic digests of the two forms.
View Article and Find Full Text PDFIn Vitro Cell Dev Biol
February 1989
Lucy Thorne Whittier Children's Center, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
The roles of glucose and insulin in the promotion of DNA synthesis in pancreatic islet cell monolayers were assessed using a variety of in vitro conditions. Several substrates including collagen, poly-l-lysine, Matrigel, and the extracellular matrix produced by cultured bovine endothelial cells (BCEM) were compared for their ability to promote monolayer growth. Islets grown on BCEM in combination with medium RPMI 1640 supplemented with 22.
View Article and Find Full Text PDFGrowth Factors
June 1990
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
The expression of basic FGF mRNA, while virtually absent in peripheral tissues, appears to be constitutively expressed in the central nervous system. As such, while it is difficult to detect any mRNA encoding basic FGF in the heart, lung, kidneys, ovaries, liver, or pituitary of rats, the levels are easily detected in brain. A regional analysis of the expression of basic FGF mRNA in brain reveals that it is widely distributed in the cortex (frontal, parietal, and occipital), the hippocampus, hypothalamus, and pons.
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 1988
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, CA 92037.
Electrophoretic analysis of murine anterior pituitary extract revealed five major proteins of Mr 13,000-18,000 (designated P13, P14, P16, P17, and P18 according to Mr), three of which, P16, P17, and P18, were markedly influenced by estradiol benzoate and perphenazine in a manner similar to that of growth hormone, and two, P13 and P14, to that of prolactin. Tyrosine peptide mapping showed partial resemblance of fingerprints for P16 and P17 (and possibly P18) to those for growth hormone, and of P13 and P14 to those for prolactin. Both P14 and P18 bound to Concanavalin A.
View Article and Find Full Text PDFEndocrinology
October 1988
Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California 92037.
As much as 40% of PRL in the pituitary gland of the pig is glycosylated. To help determine the physiological significance of this structural variant of PRL, we have measured glycosylated PRL (G-PRL) in the plasma of growing pigs from birth to 1 yr of age. An immunoblotting method developed originally for human plasma was used.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
September 1988
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
To study the pattern of release of glycosylated (G-PRL) and nonglycosylated (PRL) under various physiological conditions, we studied normal women from the first trimester of pregnancy through the postpartum period. Immunoreactive PRL variants were immunoprecipitated from 100-microL aliquots of serum, and the precipitates were subjected to gel electrophoresis in the presence of sodium dodecyl sulfate, electrotransferred to nitrocellulose paper, immunoblotted with anti-PRL serum and [125I]protein-A, and autoradiographed. The relative concentrations of the two forms of PRL were indicated by the intensity of the electrophoretic bands.
View Article and Find Full Text PDFEndocrinology
September 1988
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, Scripps Memorial Hospital, La Jolla, California 92037.
The mol wt (Mr) of intact murine PRL is approximately 23,000. Immunoblotting analysis shows a 21,000 Mr band in fresh rat and mouse pituitary extracts that cross-reacts strongly with PRL antibodies. The band becomes markedly altered by stimuli known to influence PRL secretion, such as nursing, estradiol benzoate, and perphenazine.
View Article and Find Full Text PDFEndocrinology
September 1988
Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
We have undertaken studies to determine the effect of glycosylation on the lactogenic activity of ovine PRL (oPRL). Measuring casein production in the in vitro mouse mammary gland explant assay, we found that glycosylated oPRL had 80% of the activity of oPRL. In competitive binding studies using lactogen receptors from mammary glands of lactating rabbits, glycosylated oPRL had only 20% the potency of oPRL.
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