Graduation date: 1992

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 10 uppsatser.

Thèses (Ph.D.)--Université de Sherbrooke (Canada), 2001. / Titre de l'écran-titre (visionné le 15 août 2006). Publié aussi en version papier.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references (p. 176-225).

Thesis (MMedVet. (Veterinary Tropical Diseases, Veterinary Science))--University of Pretoria, 1999. / Also available in print format.

Thesis (M.S.)--Florida State University, 2005. / Advisor: Robert J. Contreras, Florida State University, College of Arts and Sciences, Dept. of Psychology. Title and description from dissertation home page (viewed Jan. 26, 2006). Document formatted into pages; contains viii, 43 pages. Includes bibliographical references.

In vertebrates the brain superimposes control on fundamental processes such as reproduction and growth. Neuropeptides secreted from the brain initiate a cascade of events that affect these processes. In this thesis three neuropeptides are examined to determine their structures and patterns in the context of vertebrate evolution. Reproduction in vertebrates is controlled by the neuropeptide gonadotropin-releasing hormone, GnRH, a decapeptide belonging to a peptide family of twelve known members. One common theme in vertebrates is that there is usually more than one form of GnRH in the brain of a single species; often each form of GnRH has a separate location in the brain and therefore, an implied distinct function. In this thesis, the brain of Siberian sturgeon, Acipenser gueldenstaedti, initially was examined for GnRH using reversed-phase high performance liquid chromatography, HPLC, and radioimmunoassay, RIA, with specific antisera and was shown to contain mammalian (m)GnRH by chemical sequence analysis and by accurate determination of the molecular mass. In addition, another form of GnRH, termed chicken (c)GnRH-II, was found in the sturgeon brain. This is the first report to show that the primary structure of GnRH is identical in an evolutionarily-ancient fish and in mammals including humans. Further, the second form of GnRH, cGnRH-11, was identified for the first time in the brain of adult stumptail monkeys (Macaca speciosa) as well as in adult and fetal rhesus monkey (Macaca mulatta) brains. This study implies that at least two forms of GnRH are found in the brain of most vertebrate species including mammals. In cartilaginous fish that evolved earlier than sturgeon, the same HPLC and RIA methods were used to demonstrate that regions of the brain and pituitary of skate. Raja canebensis, also contained cGnRH-II but dogfish (df)GnRH rather than mGnRH. By the same criteria, teleost fish like whitefish (Prosopium williamsoni), platyfish (Xiphophorus maculatus), green swordtail (Xiphophorus hellerei) and sablefish (Anoplomia fimbria) were shown to have cGnRH-II and salmon (s)GnRH, as well as one or two more immunoreactive variants of GnRH with novel or seabream (sb)GnRH-like properties, within their brain. The identity of at least three types of immunoreactive GnRH molecules in the brain of these fish species suggests that three forms of GnRH in the brain is an early condition in teleost evolution. Ancestral sturgeon emerged at a branch point between the bony fish lineage and the tetrapod lineage and therefore, it is useful to compare the neuropeptide structures found in their brain with those both in fish and more evolutionarily-advanced vertebrates. Several tetrapod species were examined to determine if the forms of GnRH found in the sturgeon brain had been retained in their evolution. In contrasts to studies in our laboratory and by others showing that most amphibians, reptiles and birds contain two forms of GnRH, the present research shows that the brain of the green anole lizard, Anolis carolinensis, contained only cGnRH-II within its brain. In addition, my HPLC and RIA studies showed that only mGnRH was present in the brain of guinea pig, hamster and rat suggesting that there are some species which function with only one form of GnRH in their brain. Also, there were no distinguishable forms of GnRH in a human placenta, demonstrating that the type(s) of GnRH might be tissue-specific. Two neuropeptides associated with growth also were isolated from the sturgeon brain. A cDNA encoding growth hormone-releasing factor, GRF, and pituitary adenylate cyclase-activating polypeptide, PACAP, was isolated and sequenced using the polymerase chain reaction, PCR, and other molecular biology methods. In contrast to mammals where GRF and PACAP are encoded on separate genes, in sturgeon, GRF and PACAP are encoded in tandem on a single mRNA. In this thesis, I establish the structure of GnRH, GRF, and PACAP in sturgeon, a species that evolved near a critical branching point between bony fish and tetrapods. These structures are used as a focal point for comparison to those of other vertebrates. This comparative evolutionary approach is an important step toward understanding the evolution of these important neuropeptides as well as enhancing our knowledge of general principles in the endocrine systems controlling reproduction and growth. / Graduate

Please read the abstract in the section 00front of this document / Dissertation (MMed Vet (FER))--University of Pretoria, 1999. / Veterinary Tropical Diseases / unrestricted

No description available.

The characteristics of transport by the epithelial, proton-coupled oligopeptide transporter, PepT1, have been investigated in PepT1 expressing Xenopus laevis oocytes using electrophysiological techniques. Membrane depolarisations and inward currents have been measured in response to various dipeptide substrates, including structurally modified and charged peptides. The latter part of this study has focussed on the role of phorbol esters on the regulation of PepT1-mediated peptide transport. I have shown that transport of neutral peptides is dependent on both pH and membrane potential. In addition, the carboxyl terminus plays an important role in substrate recognition and binding, as when blocked, the affinity of the substrate is reduced 10-fold. The importance of position of charge within a dipeptide on substrate binding has also been investigated using dipeptides where the charged amino acid residue is present at either the amino or carboxyl terminus. The results showed that the apparent order of affinity reversed upon extracellular acidification, thus charged residues within the peptide play an important role in substrate binding. The acute regulation of the oligopeptide transporter has been examined by studying the effects of phorbol esters on the transport of a neutral peptide, Gly-Gln. The active ester, PMA, was shown to decrease both the K_a and the I_max. Immunocytochemical studies have confirmed the electrophysiological findings.