In Experiment 1, 12 cyclic mares were assigned randomly to one of two groups (n = 6/group): 1) Control, saline; and 2) GnRH, 100 mu g/h. Between 3 and 6 d after ovulation (Day 0), Alzet osmotic minipumps (Model 2ML1) containing saline or GnRH were placed subcutaneous and connected to a jugular infusion catheter. Five-min samples were collected from the intercavernous sinus (ICS) of 10/12 mares (5/group) during 8 h on Day 4, followed by an additional 6-h intensive sampling period 36 h after induced luteal regression (Day 6). Treatment with GnRH markedly increased (P < 0.01) secretion of LH during both luteal and follicular phases. During the luteal phase, treatment with GnRH eliminated the very large, intermittent secretory episodes of LH characteristic of controls and produced frequent episodes of LH release of short duration. In Experiment 2, 12 anovulatory mares and 3 mares with some residual follicular activity (n = 15) were used during the fall (December 5 to 20) and winter (February 15 to 29) seasons. Mares were assigned randomly to: 1) Control, 2) GnRH-20; continuous infusion of GnRH at 20 mu g/h, or 3) GnRH-100; continuous infusion of GnRH at 100 mu g/h. Treatments were administered subcutaneously for 14 d using Alzet minipumps. Both the 20- and 100-mu g/h treatments increased (P less than 0.01) mean circulating concentrations of LH compared to controls before the winter solstice, but mares did not respond to the GnRH- 20 dose after the winter solstice. GnRH-100 caused a seasonally-independent increase (P less than 0.0001) in follicle size and ovulation frequency compared to controls The equine gonadotrope responded to continuous administration of high-dose GnRH during both ovulatory and anovulatory seasons, but was less responsive late compared to early in the anovulatory season.

Four experiments were conducted to test the hypothesis that RF-amide related peptide 3 (RFRP3) negatively regulate the secretion of LH in mares. In Exp. 1, mares received native gonadotropin-releasing hormone (GnRH) continuously at a rate of 20 microgram/h, delivered subcutaneously using Alzet osmotic pumps during the luteal phase of the estrous cycle. Mares were treated with i.v. bolus injections of 0, 500 and 1,000 microgram eRFRP3 on days 4, 6 and 8 of cycle. Mean concentrations of LH in the peripheral circulation averaged 1.2 +/- 0.2 ng/mL and did not differ among groups before or following RFRP3 treatment. In Exp. 2, pituitary venous effluent was sampled for characterization of episodic release of LH. Mares received either saline or eRFRP3 (250 microgram) i.v. every 10 min for 6 h beginning 2 h after onset of sampling. At hour 6, each mare was challenged with 1 mg GnRH. Neither mean ICS concentrations of LH (1.3 +/- 0.2 ng/ml), nor frequency (3.6 +/- 0.55 episodes/h), amplitude (0.2 +/- 0.03 ng/ml), or duration (36.3 +/- 3.5 min) of individual secretory episodes, differed between groups before or after eRFRP3 treatment. Area under the GnRH-induced LH curve (arbitrary units) also did not differ between control and RFRP3 treated mares (175.9 +/- 11.4 vs. 192.6 +/- 10.6). In Exp. 3, winter anovulatory mares (n=6) were treated continuously for 7 d with GnRH (100 microgram/h) to stimulate synthesis of LH and increase circulating concentrations of LH to values similar to the breeding season. The ICS was catheterized for blood sampling and mares were treated with saline or RFRP3 (5 mg) in a replicated Latin square design. Treatment with RFRP3 failed to alter ICS mean concentration of LH (0.95 +/- .03 ng/ml). Finally in Exp. 4, mares in the follicular phase of the estrous cycle were assigned randomly to receive either saline (n=3) or 10 microgram/kg BW of oRFRP3 (n=3) in a single injection. No effect on mean concentration of LH was observed. In contrast to observations in birds and other mammals, results of the current experiments fail to provide evidence for functional activity of eRFRP3 or oRFRP3 in regulating LH release in the mare.

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Thesis (M. Sc.)--University of Hong Kong, 1974. / Typescript.

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

No description available.

published_or_final_version / Zoology / Master / Master of Philosophy

No description available.

Spring-born ram lambs were used to examine: (1) sexual maturational changes in LH, FSH and prolactin (PRL) secretion, testicular gonadotropin receptors, and testicular size and function; (2) predictability of yearling ram reproductive function from juvenile testicular size and reproductive hormone measurements. Despite continuous increases in testis size, serum LH-profile characteristics became greatest between 2 and 4 months and declined thereafter. However, LH-peak frequency increased by about 2-fold between 6 and 7 months; this was associated with marked increases in testosterone (T) secretion and spermatogenic function. Mean FSH and PRL levels were maximum at 2 months and 3 to 5 months, respectively, and decreased thereafter. Increases in steroidogenic and spermatogenic function were due partly to increases in testicular content of LH and FSH receptors. Yearling ram testis size and spermatogenic function were predictable from testis size at 5 to 6 months, neonatal (50 days) secretion of LH and T, and pubertal (150 days) secretion of T. However, combinations of testicular size and reproductive hormone measurements provided greater predictive power.

Research Doctorate - Doctor of Philosophy (PhD) / Background: Autoimmune diseases arise from the breakdown of central tolerance resulting in the escape of self reactive T-lymphocytes from the thymus to the periphery. As a group of conditions, autoimmune diseases occur in approximately 5% of the general population and represent the third most common cause of morbidity, placing considerable expenses on the health care system and society. Understanding the underlying pathogenesis and pathophysiology of these diseases is therefore important for the correct diagnosis and treatment of these patients. While some autoimmune diseases have been paid particular attention, little is known about the pathogenesis of the pituitary autoantibodies. Aims: To identify target autoantigens in the pituitary autoimmune disease lymphocytic hypophysitis and autoantigen(s) relating to pituitary manifestations in APS1 patients. Methods: A pituitary cDNA expression library was immunocreened with lymphocytic hypophysitis and APS1 patient sera to identify target autoantigens. These were then tested in an ITT assay for autoantigen specificity to relating to the disorders. Immunofluorescence of pituitary tissue was performed to determine the cell types targeted in the disorders. Results: Two APS1 autoantigens were identified, a major autoantigen ECE-2 and a minor autoantigen TSGA10, although neither apparently correlated to pituitary manifestations in APS1. T-box 19 was also identified as a significant minor autoantigen in 10.5% of lymphocytic hypophysitis patients. Immunoreactivity in a single lymphocytic hypophysitis patient against cells of the intermediate lobe of the guinea pig pituitary is also reported. Discussion: Immunoscreening a target organ cDNA expression library is a valuable method for identifying novel autoantigens, with immunopreciptation assay a quick and reliable method for analysing a large cohort of patients for autoantibodies. We have identified another two APS1 autoantigens and the first significant autoantigen in lymphocytic hypophysitis. While further characterisation of these autoantigens are required, these novel findings broaden our current understanding of pituitary autoimmunity.