No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

The role of selected hormones in the control of hair follicle activity, fibre growth and moult in cashmere goats was investigated by manipulation of prolactin (PRL), thyroid hormones, and growth hormone (GH) individually or in combination. In experiment 1, the effect of different doses of the anti-thyroid drug "propylthiouracil" (PTU), on thyroxine (T4) and triiodothyronine (T3) profiles and deiodinase enzyme activities in liver, kidney and skin tissues was determined. Types II and III deiodinase enzymes were found to be present in goat skin but not type I. It was concluded that the supply of T3 within the skin was partly independent of circulating hormone profiles. In experiment 2, goats were treated with PTU, triiodothyronine (T3) and bromocriptine (Br) to decrease T3 availability to tissues and circulating PRL concentrations, respectively. Treatment with Br delayed the spring rise in plasma PRL concentrations (P=0.06) and primary (P<0.05) hair follicle activity, and delayed moult onset (P<0.01). PTU treatment did not significantly affect hair follicle activity but generally delayed the time of moult onset (P<0.05). The effects of the treatments were not additive, indicating that the actions of the two hormones were not independent. The effects of PTU and Br treatments were not exerted through changes in IGF-I binding activity in the skin, but binding was greater (P<0.01) in April than November. In experiment 3, treatment with bovine somatotropin (bST), T4 or metoclopramide to increase circulating concentrations of GH, T4 or PRL, failed to prolong the period of anagen in hair follicles, but bST increased fibre growth rate (P<0.05) and this was associated with higher circulating IGF-I concentrations. It is concluded that manipulation of the cycle of the cashmere-producing hair follicle is unlikely to be achieved through manipulation of circulating hormone concentrations alone and that much regulation of hair follicle activity occurs within the skin itself, possibly through changes in enzymes that control the supply of T3 to the follicles, in hormone receptor activity, and in the rate of synthesis of IGF-I and other growth factors within the skin.

Reproductive neuroendocrine activity and appetite are modulated at the hypothalamus by both nutritional status and photoperiod in the seasonal animal. The objectives of this work were (1) to measure circulating hormones and/or metabolites that relay information about peripheral nutritional status to the hypothalamus, (2) to identify which hypothalamic neuropeptides and receptors that are responsive to photoperiodic and nutritional feedback and (3) to establish which changes in peripheral signals and/or hypothalamic neuropeptides are associated with alterations in the activity of the reproductive neuroendocrine axis. Three main experiments were carried out. The first experiment (Chapter 1) utilised a 2 x 2 design to examine the separate and interactive effects of photoperiod and food restriction on hypothalamic neuropeptide and receptor mRNA expression and on GnRH/LH secretion. In the second experiment (Chapter 2), two components of nutritional status, BC and increased food intake were investigated since both are positively related to reproductive performance in sheep. In the final experiment (Chapter 3) the approach was to use an exogenous treatment to artificially raise plasma insulin in an attempt to "drive" some of the foregoing effects. Collectively these studies have lead to the first localisation AgRp, MCH, orexin, Mc3R, Mc4R gene expression in the ovine hypothalamus. They indicate that circulating insulin and leptin are major factors relaying information about nutritional status to the hypothalamus. In addition, they have dissociated BC and food intake as signals to the hypothalamus. Moreover these studies have provided no evidence that NPY, AgRp, POMC, MCH and ObRb play a role in driving seasonal changes in appetite and gonadotrophin secretion. However they do suggest NPY-ergic and melanocortin pathways are important in maintaining appetite/bodyweight/energy homeostasis or restoring energy balance following perturbation. Furthermore the results show that changes in nutrient-sensitive hypothalamic neuropeptide and receptor gene expression may not necessarily lead to alterations in the activity of the reproductive neuroendocrine axis. However, they do indicate that increased NPY biosynthesis during food restriction may be involved in the inhibition of pulsatile GnRH/LH release.

PhD,School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand / Tissue specific regulation of the progesterone receptor is central to female health. The synthetic steroid, RU486 is a partial progesterone and oestrogen receptor antagonist, functioning to actively silence progesterone receptor gene associated transcription. For this reason, it has been used both as a contraceptive and quite controversially as an abortive agent. In this study, both cellular and gene specific effects of RU486 were investigated in a rat model of early pregnancy, this including the key phases of the plasma membrane transformation, the window of receptivity and early implantation. As all of these stages are hormonally regulated by progesterone and oestrogen, the focus here was to elucidate the mechanisms of action of a single dose of RU486, used as a postcoital contraceptive, at day 3.0 of pregnancy, to successfully prevent implantation of a viable blastocyst and subsequent pregnancy. In association with the cellular preparation of uterine epithelial cells for implantation, selected molecular targets and events were investigated at a protein and gene expression level, both prior to and after RU486 treatment, to assess the effects of either a deficit or excessive expression of these gene products on uterine preparation and eventual implantation. Factors here included the progesterone receptor, markers of apoptosis (Bax and Bcl2), mediators of angiogenesis (VEGF, bFGF and PDGF) and biomarkers of endometrial implantation (LIF, Calcitonin and Muc-1). Together, an ultrastructural and light microscopy analysis showed RU486 to morphologically alter the uterine endometrial cells and to disrupt the plasma membrane transformation of early pregnancy, predisposing these cells towards apoptosis. In association with this, progesterone receptor gene and protein expression was ubiquitously decreased throughout pregnancy. With regards to the implantation process of early pregnancy, the luminal epithelial cells undergo apoptosis to allow the hatching blastocyst to penetrate and implant within the uterine wall. This is partially mediated by the ratio of the expression of the apoptotic factors Bax and Bcl-2. Surprisingly here, RU486 caused an overall anti-apoptotic environment, despite previously observed high levels of apoptotic activity. This indicates that factors other than Bax and Bcl-2 influence the RU486-induced apoptosis. A crucial event of early pregnancy is the establishment of an adequate blood supply to sustain and nourish the implanting blastocyst. There was a decided reduction in the angiogenic response of early pregnancy, as a direct consequence of RU486 treatment; the normally high levels of VEGF and bFGF during early pregnancy, were markedly decreased at all three days of pregnancy. This was reflected in the lack of increased vascularisation as normally signalled by the indicator dye, Pontamine Sky blue. In contrast to the overall increase in VEGF and bFGF at the time of blastocyst implantation during early pregnancy, increased PDGF expression was localised to the implantation sites, strongly suggesting a role for this angiogenic factor in endothelial cell proliferation. v The endometrial biomarkers are indicative of implantation, their expression patterns varying around the phase of implantation. These markers are essential to implantation, as when LIF and Calcitonin are deregulated and Muc-1 persists on the apical surface of the endometrium, implantation fails. These events are precisely what occur following RU486 treatment. In summary, the overall effects of RU486 in the rat model of early pregnancy, when used as a postcoital contraceptive, indicate highly effective inhibition of progesterone and oestrogen effects on the endometrium, mediated by their receptors. More specifically, the structural and molecular events mirror those described in ovariectomised animal models, suggesting a hormonally under-stimulated endometrium. Clearly from the present study, the precise priming of the endometrium in preparation for blastocyst implantation is severely impaired by RU486 through a number of signalling pathways, thus predisposing the uterus to pregnancy failure.