Biomedical subjects

F Esch

Publications and source records attributed to F Esch.

94 records · Page 6Linked to original sources

PubMedDate not supplied

The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors.

HP-1 is the most abundant human representative of a recently discovered class of neutrophil cystine- and arginine-rich peptides. These peptides have many potentially regulatory activities expressed at nanomolar concentrations. To establish the levels of HP-1 that can accumulate in human lung tumors and nondiseased lung fragments, tissues were extracted for their peptide content. The extracts were purified on reverse phase HPLC, and HP-1 and related peptides were identified by sequence analysis and their concentrations in the tissue quantitated by amino acid analysis. Immunohistochemistry was performed and strongly suggests that HP-1 is confined to granulocytes under most circumstances, and indicates that the levels of HP-1 measured in the tumors reflect the levels obtained when solid tissue is infiltrated by neutrophils. The maximum observed levels were 26 nanomoles per gram wet weight of tissue. Attempts were then made to correlate this level to the cytotoxic potential of HP-1 by performing in vitro cytotoxicity dose-response curves on several cell lines. Most cells were killed at between 1 and 8 microM, and the response depended on the growth conditions of the cells. The levels of HP-1 that accumulate in tumors can exceed the in vitro cytolytic concentrations. The levels are also considerably in excess of those required to exert in vitro regulatory actions.

Amino Acid Sequence↗

PubMedDate not supplied

Immunohistochemical detection of growth hormone-releasing factor in brain.

The concept of a hypothalamic neurohumoral control for anterior pituitary secretion postulates the existence of a growth hormone-releasing factor (GRF) of neuronal origin that stimulates the pituitary gland to release growth hormone (GH). Such a compound has not yet been isolated and characterized from the brain, although there is extensive physiological and biochemical evidence for its existence (reviewed in ref. 2). However, a 44-amino-acid amidated peptide having the physiological properties of GRF as well as chemical similarities was recently isolated from a human pancreatic tumour that had caused acromegaly. Two shorter biologically active fragments of 40 and 37 residues were also isolated. The synthetic replicates of these human pancreas GRF (hpGRF) peptides specifically stimulate GH release in vitro and in vivo. Assuming similarity or identity between the putative hypothalamic GRF and the tumour-derived hpGRF, we have used immunohistochemistry to search for hpGRF-like immunoreactivity in the brain. We report here that antisera against the hpGRF1-40 peptide specifically stain neuronal cell bodies in the arcuate nucleus of the primate hypothalamus, with fibres projecting to the median eminence and ending in contact with portal vessels. This topography is characteristic of a neuronal system elaborating a releasing factor. These results provide evidence that hypothalamic GRF is very similar, if not identical, to hpGRF.

Aged↗

PubMedDate not supplied

Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta.

Inhibin, a specific and potent polypeptide inhibitor of the secretion of follicle-stimulating hormone (FSH), of gonadal origin and thus a potential contraceptive, may constitute a missing link in the mechanism controlling the differential secretion of the pituitary gonadotropins. Inhibin-like bioactivity has been reported in various fluids and extracts of testis and in ovarian follicular fluid. Although there have been several attempts to purify inhibin from seminal plasma, purification from follicular fluid has been more successful (refs 14-16; for review see ref. 17). We have previously isolated two forms (A and B) of inhibin from porcine follicular fluid. Each form comprised two dissimilar subunits of relative molecular mass (Mr) 18,000 (18K, referred to here as the alpha-subunit) and 14K (the beta-subunit), crosslinked by one or more disulphide bridge(s). Forms A and B differ in the N-terminal sequence of their 14K subunit. Preliminary structural characterization of porcine and bovine ovarian inhibins shows that they have similar properties. Here, we have used the N-terminal amino-acid sequence data on the subunits of each inhibin to identify cloned complementary DNAs encoding the biosynthetic precursors and report that inhibins are the product of a gene family that also includes transforming growth factor-beta (TGF-beta) and whose structural organization is similar to that of pituitary and placental glycoprotein hormones.

Amino Acid Sequence↗

PubMedDate not supplied

Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin.

Inhibin is a gonadal protein that specifically inhibits the secretion of pituitary follicle-stimulating hormone (FSH). Two forms of inhibin (A and B) have been purified from porcine follicular fluid and characterized as heterodimers of relative molecular mass (Mr) 32,000 (ref. 2). Each inhibin is comprised of an identical alpha-subunit of Mr 18,000 and a distinct but related beta-subunit of Mr 13,800-14,700 linked by interchain disulphide bond(s). Throughout the purification of inhibins, we consistently observed two fractions which stimulated the secretion of pituitary FSH. We report here the isolation of one of the FSH-releasing proteins; it has a Mr of 24,000 and its N-terminal sequences up to residue 32 are identical to those of each beta-subunit of inhibins A and B. In the presence of reducing agents, SDS-polyacrylamide gel electrophoresis resolves the FSH-releasing substance into two subunits which are identical in their migration behaviour to the reduced beta-subunits of inhibins A and B. Based on the N-terminal sequence data and Mr of the intact and reduced molecules, we propose that the FSH-releasing substance, which is active in picomolar concentrations, is a heterodimeric protein composed of the two beta-subunits of inhibins A and B linked by interchain disulphide bond(s). The structural organization of the FSH-releasing substance is homologous to that of transforming growth factor-beta (TGF-beta), which also possesses FSH-releasing activity in the same bioassay. We suggest that the substance be called activin to signify the fact that it has opposite biological effects to inhibin.

Amino Acid Sequence↗