No description available.

Exogenous PGF_2α, (see Appendix I for definitions of abbreviations) is luteolytic in midluteal (1.e., d 9 of a 17 d estrous cycle) sheep. However, the pharmacokinetic responses to PGF_2α-induced luteolysis are not known. This study (Exp. 1 and 2) was conducted to determine several pharmacokinetic responses to two dosing regimens of Lutalyse® (PGF_2α). Experiment 1 was a 2 x 2 factorial design, with Lutalyse and H/Ox as main effects. Lutalyse (15 mg) was injected i.m., and blood samples were collected, relative to the time of injection, from the vena cava at points cranial and caudal to the uteroovarian vein. Progesterone and PGF_2α, were measured in blood plasma. The PGF_2α concentrations were greater in H/Ox and sham H/Ox ewes treated-with Lutalyse® than in control ewes. Peak concentrations of PGF_2α were greatest in sham H/Ox Lutalyse-treated ewes, indicating that the uterus and(or) ovaries secrete PGF_2α, in response to exogenous PGF_2α. In Lutalyse-treated ewes, progesterone concentrations decreased by 50% within 8 h after treatment. The design of Exp. 2 was also a 2 x 2 factorial, with Lutalyse (2 x 5mg at 3 h intervals) and H/Ox as main effects. Prostaglandin F_2α and PGFM were measured in blood plasma collected, relative to the time of injections, from the vena cava at points cranial and caudal to the uteroovarian vein. The PGF_2α concentrations were greater in sham H/Ox ewes treated-with Lutalyse than in control ewes. Peak concentrations of PGF_2α were greater in sham H/Ox than in ewes in all other treatment groups, indicating again that the uterus and(or) ovaries secrete PGF_2α in response to exogenous PGF_2α In general, PGFM concentrations increased in a pattern similar to that of PGF_2α after Lutalyse injection; although there was a short delay of approximately 2 min. Caudal vena caval PGF, concentrations in H/Ox Lutalyse-treated ewes were greater than that after saline injection, which indicates that metabolism may depend on the presence or absence of the uterus and(or) ovaries. In Exp. 1, caudal PGF, concentrations were greater in H/Ox ewes injected with 15 mg of Lutalyse than in ewes in all other treatments . However, in response to 5 mg Lutalyse, caudal PGF_2α concentrations were greater in sham H/Ox ewes than in all other treatment groups. This indicates that the larger dose in H/Ox ewes supersedes the capacity of the lung and kidney to dispose of PGF_2α, and PGF_2α is more tightly regulated in intact ewes. The lungs and kidney are capable of metabolizing the smaller dose of Lutalyse but not the resulting PGF_2α production in intact ewes. A short validation experiment was conducted to determine the effects of sampling location on progesterone, PGF_2α and PGFM concentrations. Sampling location did not affect the mean concentration of progesterone or PGFM. However, location affected the mean PGF_2α concentration. The concentration of PGF_2α, was greater (P < .05) in saphenous vein and caudal vena caval blood plasma than in jugular plasma. In summary, the uterus and(or) ovaries produce and regulate PGF_2α concentration in response to Lutalyse. It is speculated that a threshold PGF_2α concentration or duration of the PGF_2α peak concentration exists because these PGF_2α, responses differed in intact Lutalyse-treated and saline-treated ewes in both experiments. The mean cranial PGF_2α concentration, peak concentration, duration of the peak, increase in PGF_2α and AUC were greater in response to 15 mg of Lutalyse, although the two smaller doses have been shown to be more efficacious in inducing luteolysis. The second dose of PGF_2α may act by mimicking pulses of PGF_2α and initiate the luteolytic cascade two times. / Master of Science

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: This study describes: • the comparison of the enzymatic activities of the two ovine cytochrome P450 17 - hydroxylase/17,20-lyase (CYP17) isoforms expressed in non-steroidogenic COS-1 cells. The Km and Vmax values for the metabolism of pregnenolone and progesterone were determined, while time-dependent metabolism of pregnenolone, 17-hydroxypregenolone, progesterone and 17-hydroxyprogesterone was also reported. The cloning and sequencing of ovine cytochrome b5 is reported and was co-expressed with CYP17. The results showed that the wild type 1 (WT1) isoform of ovine CYP17 produce more cortisol precursors than the wild type 2 (WT2) isoform; • the analysis of the frequency distribution of the CYP17 genotypes within a South African Merino population, which were divergently selected for (H-line) or against (L-line) the ability of a ewe to rear multiple offspring per birthing opportunity. It was observed that the CYP17 frequency distribution was the same within the H- and L-line, with 78.3 % heterozygous WT1/WT2 and 21.7 % homozygous WT1/WT1. No homozygous WT2/WT2 individuals were identified; • the development of a UPLC-MS/MS method for the separation and quantification of all thirteen adrenal steroids that are produced in the adrenal gland; • the relative contribution of the CYP17 genotypes in the total steroidogenic output in adult adrenocortical cells from the adrenal glands of H- and L-line sheep, with particular emphasis on cortisol production. The adrenocortical cells from the H-line sheep showed a marked higher cortisol production than the L-line, while adrenocortical cells from homozygous WT1/WT1 sheep also produced more cortisol than heterozygous WT1/WT2 sheep; • the blood cortisol responses upon the stimulation of the HPA axis by insulin induced hypoglycaemia of the H- and L-line sheep with known CYP17 genotypes. It was observed that the CYP17 genotype and selection line are important factors affecting the cortisol responses of sheep, where L-line heterozygous WT1/WT2 sheep showed the lowest cortisol response and glucose recovery; • the association of the CYP17 genotype with behavioural responses of H- and L-line sheep to flock isolation stress, as well as the association of the CYP17 genotype with ewe reproduction and lamb output. While reproduction seemed to be unaffected by the CYP17 genotype, the behavioural stress responses of sheep to flock isolation correlated with the CYP17 genotype, where the heterozygous WT1/WT2 genotype was associated with a wilder nature. / AFRIKAANSE OPSOMMING: Hierdie studie ondersoek: • die vergelyking van die ensiemaktiwiteite vir twee isoforme van skaap sitochroom P450 17 -hidroksilase/17,20-liase (CYP17), wat uitgedruk was in nie-steroïed genererende COS- 1 selle. Die Km and Vmax waardes was bepaal vir die metabolisme van pregnenoloon en progesteroon, terwyl die tyd-afhanklike metabolisme van pregnenoloon, 17- hidroksiepregnenoloon, progesteroon en 17-hidroksieprogesteroon ook gerapporteer word. Die klonering en volgorde bepaling van skaap sitochroom b5 was gedoen en gevolglik was sitochroom b5 saam met CYP17 uitgedruk in COS-1 selle. Die resultate het gewys dat wilde tipe 1 (WT1) meer voorlopers van kortisol produseer as wilde tipe 2 (WT2); • die frekwensie distrubusie van die CYP17 genotipes in ‘n Suid-Afrikaanse Merino populasie, waar skape in teenoorgestelde rigtings geselekteer was vir (H-lyn) of teen (L-lyn) die vermoë van ‘n ooi om geboorte te gee aan veelvoudige lammers per lamgeleentheid. Die frekwensie distrubusie van CYP17 was dieselfde in beide die H- en L-lyn, waar 78.3 % van die populasie heterosigoties WT1/WT2 en 21.7 % homosigoties WT1/WT1 was. Geen homosigote WT2/WT2 individue was geïdentifiseer nie; • die ontwikkeling van ‘n UPLC-MS/MS metode vir die skeiding en kwantifisering van al dertien steroïede wat natuurlik geproduseer word in die bynier van die skaap; • die relatiewe bydrae van die CYP17 isoforme tot die totale steroïedale uitsette vanuit die bynier kortex selle, vanaf die byniere van H- en L-lyn skape, waar klem geplaas word op die produksie van kortisol. Die bynierselle van die H-lyn skape het aansienlik meer kortisol produseer as die L-lyn, terwyl die bynierselle van die homosigotiese WT1/WT1 skape ook meer kortisol produseer het as heterosigotiese WT1/WT2 skape; • die bloed kortisol in reaksie tot die stimulering van die hipotalamus-hipofise-adrenale aksis, deur insulien geïnduseerde hipoglisemiese stress, in skape van die H- en L-lyne met bekende CYP17 genotipes. Dit was gevind dat die kortisol reaksie geaffekteer word deur beide die CYP17 genotipe en seleksie lyn, waar L-lyn heterosigotiese WT1/WT2 skape die minste kortisol geproduseer het en die stadigste herstel van glukose vlakke getoon het; • die assosiasie tussen die CYP17 genotipe en die gedrags reaksies op trop-isolasie, sowel as ooi-reproduksie en lamuitset, van die H- en L-lyn skape. Die reproduksie parameters was onafhanklik van die CYP17 genotipe, terwyl ‘n sterk assosiasie gevind was tussen die CYP17 genotipe en gedrags reaksies op trop-isolasie. Die heterosigotiese WT1/WT2 skape het ‘n wilder natuur getoon gedurende trop-isolasie in vergelyking met homosigotiese WT1/WT1 skape.

"May 2002" Includes bibliographical references (leaves 148-164) Describes a series of novel experiments designed to enhance our understanding of nutrient utilisation for growth of wool and the whole body.

xxiii, 222 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Insulin-like growth factor-I circulates at high concentrations in blood, mainly complexed with IGF-binding proteins. The main objective of the thesis is to determine the general role played by plasma IGF-binding proteins in the regulation of IGF transfer from blood to tissues. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1994

"May 2002" / Includes bibliographical references (leaves 148-164) / xi, 164 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes a series of novel experiments designed to enhance our understanding of nutrient utilisation for growth of wool and the whole body. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 2002

No description available.

Bibliography: leaves 148-160. / xix, 160, [40] leaves, [19] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the process of neovascularization of intervertebral disc components, with ageing and in disease. Establishes the extent of end plate vascularization in the lumbar discs of young normal sheep, and demonstrates that some components of the disc undergo neovascularization in response to physical trauma, possibly as a part of tissue repair response. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1996?

Thesis (MSc)--University of Stellenbosch, 2006. / ENGLISH ABSTRACT: Premature luteal regression occurs on average in 30% of superovulated sheep ewes. This phenomenon occurs early in the cycle before the embryo’s can be collected and is a major contributor to failure in embryo transfer programs. This research was done to understand the physiological mechanisms involved. Chapter two provides a general background of the physiology of natural luteolysis and the maternal recognition of pregnancy. The chapter introduces some new concepts on the topic of cell death and provides a recent literature review on research done on the phenomenon of premature luteal regression. This chapter forms the base of ideas and arguments that follows in the two studies containing new original work in this field. The research contained in this thesis comprises of two in vivo studies. The first study (Chapter 3) compare premature luteal regression to Prostaglandin F2α (PGF2α) induced regression with emphasis on the changes in levels of the steroid hormones progesterone (P4) and estradiol - 17β (E2-17β) and changes in structure and ultra structure. The following conclusions were made: 1. Premature luteal regression is not merely inadequate luteal support, but indeed early luteal regression, since seasonal influences could merely be nutritional influences, and a definitive increase in P4 were recorded in animals exhibiting the phenomena. 2. Nutritional influences could play a role, but the type and quality of nutrients and mechanism involved, is still unclear. 3. PGF2α-induced regression differs from premature luteal regression in that: a) The progression of functional and structural regression in PGF2α -induced regression is slower than in premature luteal regression. b) Regressed corpora lutea do not occur with normal functioning corpora lutea. 4. There is a distinct second E2-17β peak preceding the decline in P4 in animals that exhibits signs of premature luteal regression. A threshold initiating premature luteal regression was not established. The second study (Chapter 4) compares the changes in the ovine β estradiol - 17 β receptor (oERβ) between premature luteal regression and PGF2α induced regression. The study concludes that there could be a potential role for oERβ in premature luteal regression. The findings of these two studies raise some questions about the conventional perception that early release of PGF2α is the cause of premature luteal regression. The thesis concludes in a hypothesis (Chapter 4) explaining the phenomenon. / AFRIKAANSE OPSOMMING: Premature luteale regressie kom gemiddeld in 30% van gesuperovuleerde skaap-ooie voor. Die verskynsel kom vroeg in die siklus voor, voor die embrios gekollekteer kan word, en is een van die belangrikste oorsaake van mislukkings in ‘n embrio-oorplaasingsprogram. Die huidige navorsing poog om die fisiologiese meganismes betrokke by premature luteale regressie te verstaan. Hoofstuk twee verskaf ‘n algemene agtergrond van die fisiologiese aspekte betrokke by natuurlike luteale regressie en maternale herkenning van swangerskap. Die hoofstuk stel nuwe konsepte voor oor sel afsterwing en verskaf ‘n opgedateerde literatuuroorsig met betrekking tot die navorsing wat in die veld oor die verskynsel gedoen is. Die hoofstuk vorm die basis vir die idees en argumente, wat volg in die twee studies en wat oorspronklike nuwe navorsing bevat oor die onderwerp. Die navorsing in die tesis bestaan uit twee in vivo studies. Die eerste studie (Hoofstuk 3) vergelyk premature luteale regressie en prostaglandien F2α (PGF2α) ge-induseerde regressie met ‘n klem op die vlakke van die steröiedhormone progesteroon (P4) en estradiol - 17β (E2-17β) en veranderinge in die mikroskopiese struktuur en ultra struktuur van die corpus luteum. Die studie bevind: 1. Premature luteale regressie is nie slegs onvoldoende luteale funksie nie, maar vroë luteale regressie aangesien seisoenale invloede eitlik voedings invloede kan wees en P4 gestyg het in diere waar die verskynsel voorgekom het. 2. Voeding kan ‘n rol speel maar die tiepe en gehalte van die voedingstowwe en die meganismes betrokke is nie duidelik nie. 3. PGF2α - ge-induseerde regressie verskil van premature regressie in dat: a) Die verloop van funksionele en strukturele regressie is stadiger in PGF2α - ge-induseerde regressie in vergelyking met premature luteale regressie. b) Corpora lutea wat regressie ondergaan het kom nie voor saam met corpora lutea wat normal voorkom nie. 4. Daar die ‘n duidelike tweede piek van E2-17β gaan die afname in P4 vooraf in diere waar premature regressie voorkom. 5. Daar is nie geslaag om ‘n drempel vas te stel waar premature regressie ge-inisieer word nie. Die tweede studie vergelyk die veranderinge in estradiol-17β reseptore (oERβ) in die skaap tydens premature luteale regressie en PGF2α geinduseerde regressie. Die studie bevind dat daar ‘n moontlike rol is vir ERβ in premature luteale regressie. Die bevindinge van die twee studies bevraagteken die konvensionele opvatting dat vroë vrystelling van PGF2α verantwoordelik is vir premature luteale regressie. Die tesis sluit af met ‘n nuwe hipotese om die verskynsel te verduidelik.

Includes bibliographical references (leaves 188-217) Insulin-like growth factor-I circulates at high concentrations in blood, mainly complexed with IGF-binding proteins. The main objective of the thesis is to determine the general role played by plasma IGF-binding proteins in the regulation of IGF transfer from blood to tissues.