Graduation date: 2003

[Truncated abstract] Reproductive activity is affected by external factors such as photoperiod, social cues, stress and nutrition, all of which can alter the pulsatile activity of the GnRH neurons, which is the major neuroendocrine system used by the brain to control gonadal function. In the male Merino sheep, nutrition is one of the most powerful factors that affect pulsatile LH secretion, used commonly to bioassay GnRH neuronal activity. More accurately, the reproductive system responds to “metabolic status”, rather than “nutrition”, and the three factors that contribute to metabolic status are food intake, the amount of body reserves and the rate of energy expenditure ... In this thesis, I tested the general hypothesis that the metabolic hormones and hypothalamic neuropeptides that are known to control food intake also mediate the effect of metabolic status on the activity of the GnRH neurons ... In conclusion, the results from my experiments provide some insight into the mechanisms by which metabolic status affects reproductive activity in male sheep. Plasma insulin, which changes with alterations in metabolic status, appears to play a critical role in the regulation of GnRH neuronal activity. The level of leptin seems to have a permissive role only in lean animals. Orexins acting via OX2 receptors could be involved in the activation of reproductive function following an acute increase in nutrition. However, the neuropeptidergic systems can not be ruled out because they might be involved in very early steps of responses to nutrition.

[Truncated abstract] The activity of the reproductive endocrine axis is the result of interactions among many organs and tissues, particularly the hypothalamus, pituitary gland and gonad. However, it depends on more than the communication between anatomical structures because it is also affected by genotype, internal factors (e.g., metabolic inputs) and external factors (e.g., photoperiod, socio-sexual cues, stress, nutrition). This multifactorial complexity makes it difficult to use animal experimentation to investigate the pathways and mechanisms involved. Therefore, in this study, I have turned to mathematical modelling. The general hypothesis was that, by modelling the hormonal feedback loop that links the hypothalamus, pituitary gland and gonad, I would be able to discover the critical control points in this homeostatic system. This would allow me to inform and direct research into the processes that control reproduction, including inputs from environmental factors. My studies began with the development of a model of the negative feedback loop through which testosterone controls the secretion of pulses of gonadotrophin-releasing hormone (GnRH) by the hypothalamus. The model incorporated two critical factors: testosterone concentration and a time delay in the inhibition of the activity of the GnRH 'pulse generator' by testosterone. The general assumptions were: i) there are two positive feedforward processes (GnRH pulses stimulate LH pulses, and, in turn, LH pulses stimulate testosterone secretion); ii) testosterone exerts negative feedback that reduces the frequency of GnRH pulses. The model incorporated a group of equations that represent the GnRH pulse generator, through which the inhibitory effect of testosterone acted to reduce GnRH pulse frequency. Simulations were run with various values for the time delay in feedback and, as model development progressed, the simulations were extended to include combinations of time delays and levels of sensitivity of the GnRH pulse generator to inhibition by testosterone. The output of the simulations showed clearly that a time delay in negative feedback, as well as the concentration of testosterone, can greatly affect the frequency of GnRH pulses and the shape of the GnRH secretory profile. Importantly, the effect of the time delay depends on the sensitivity of the pulse generator to testosterone. In addition, the simulations suggested two additional components that might be involved in the control of the GnRH pulse generator: i) a delay in the rate of adaptation to a change in steroid feedback; and ii) a minimum pulse interval (maximum frequency). These studies iii therefore suggest that the regulation of the activity of the GnRH pulse generator, and thus the frequency and profile of GnRH and LH pulses, requires interactions among these four components. These interactions should be tested in animal experimentation. In the next stage, I extended the model so I could test whether the feedback delay might involve the process of aromatization in which testosterone is converted to oestradiol at brain level. ... This information can be used to direct future experimental studies that will help us to understand the factors that underlie the dynamic behaviour of the hypothalamic and pituitary systems that control reproduction.

Typescript. / "April 1987." / Includes bibliograpical references (leaves 160-194). / xii, 194 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Presents direct comparative information on growth and endocrinological aspects of reproductive development in intact and gonadectomized male and female Merino lambs born in autumn and treated prepubertally with either a non-aromatizable androgen (trenbolone acetate) with higher androgenic potency than testosterone, oestradiol -17beta(oestradiol), or a combination of these two steroid hormones. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1988

Includes bibliographical references (leaves 166-195) Addresses the nature of the central mechanisms involved in the regulation of the circadian pattern of secretion of the pineal hormone melatonin in the highly seasonal Suffolk breed of sheep. Provides new information on the behaviour of the onset and offset of melatonin secretion under different photoperiodic conditions.

Includes bibliographical references (leaves 166-195) / xxi, 195 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Addresses the nature of the central mechanisms involved in the regulation of the circadian pattern of secretion of the pineal hormone melatonin in the highly seasonal Suffolk breed of sheep. Provides new information on the behaviour of the onset and offset of melatonin secretion under different photoperiodic conditions. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1991?